CAM 20138

Transesophageal Endoscopic Therapies for Gastroesophageal Reflux Disease

Category:Medicine   Last Reviewed:December 2019
Department(s):Medical Affairs   Next Review:September 2020
Original Date:December 2000    

Description
Gastroesophageal Reflux Disease
Gastroesophageal reflux disease (GERD) is defined as reflux of stomach acid into the esophagus that causes symptoms and/or mucosal injury. GERD is a common medical disorder, with estimates of 10% to 20% prevalence in developed countries. The severity of GERD varies widely. Many patients have mild, intermittent symptoms that do not require treatment or only require episodic use of medications. Other patients have chronic, severe GERD that can lead to complications such as Barrett esophagus and esophageal cancer.

Treatment
For patients with severe disease, chronic treatment with acid blockers is an option. For some patients, medications are inadequate to control symptoms; other patients prefer to avoid the use of indefinite, possibly lifelong medications. Surgical treatments are available for these patients, primarily a Nissen fundoplication performed either laparoscopically or by open surgery. A number of less invasive procedures are also being evaluated as an intermediate option between medical therapy and surgery.

The LINX Reflux Management System is composed of a small flexible band of 10 to 18 interlinked titanium beads with magnetic cores. Using standard laparoscopic techniques, the band is placed around the esophagus at the level of the gastroesophageal junction. The magnetic attraction between the beads is intended to augment the lower esophageal sphincter to prevent gastric reflux into the esophagus, without compressing the esophageal wall. It is proposed that swallowing food or liquids creates sufficient pressure to overcome the magnetic bond between the beads, allowing the beads to separate and temporarily increase the size of the ring. The target population is patients who have GERD symptoms despite maximum medical therapy (eg, proton pump inhibitors) but who do not want to risk the adverse effects of a surgical procedure like Nissen fundoplication. Adverse events of the LINX Reflux Management System may include dysphagia or odynophagia. The device can be removed by a laparoscopic procedure if severe adverse events occur or if magnetic resonance imaging is needed for another condition.

Summary
A laparoscopically implanted ring composed of interlinked titanium beads with magnetic cores has been developed for the treatment of gastroesophageal reflux disease (GERD). The device is placed around the esophagus at the level of the gastroesophageal junction and is being evaluated in patients who have GERD symptoms, despite maximal medical therapy.

For individuals who have GERD who receive magnetic sphincter augmentation (MSA), the evidence includes prospective and retrospective observational comparative studies, 2 single-arm interventional trials, and single-arm observational studies. Relevant outcomes are symptoms, change in disease status, medication use, and treatment-related morbidity. In the 2 single-arm, uncontrolled manufacturer-sponsored studies submitted to the U.S. Food and Drug Administration with materials for device approval, subjects showed improvements in Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) scores and reduced proton pump inhibitor use. Similarly, observational comparative studies, most often comparing MSA with laparoscopic Nissen fundoplication, generally have shown that GERD-HRQL scores do not differ significantly between fundoplication and MSA, and patients can reduce proton pump inhibitor use after MSA. However, the comparative studies are retrospective and nonrandomized, may be affected by selection bias, and the subjective outcome measures used in these studies (eg, the GERD-HRQL scores) may be biased. A randomized trial is in progress (NCT02505945); it will compare treatment with the MSA and treatment with double-dose proton pump inhibitors. Randomized comparisons of MSA with laparoscopic Nissen fundoplication are also needed to evaluate the relative risk-benefit of these 2 procedures. The evidence is insufficient to determine the effects of the technology on health outcomes.

Background
Gastroesophageal Reflux Disease
Gastroesophageal reflux disease (GERD) is a common disorder characterized by heartburn and other symptoms related to reflux of stomach acid into the esophagus. Nearly all individuals experience such symptoms at some point in their lives; a smaller number have chronic symptoms and are at risk for complications of GERD. The prevalence of GERD has been estimated to be 10% to 20% in the Western world, with a lower prevalence in Asia.1,

Pathophysiology
The pathophysiology of GERD involves excessive exposure to stomach acid, which occurs for several reasons. There can be an incompetent barrier between the esophagus and stomach, either due to dysfunction of the lower esophageal sphincter or incompetence of the diaphragm. Another mechanism is abnormally slow clearance of stomach acid. In this situation, delayed clearance leads to an increased reservoir of stomach acid and a greater tendency to reflux.

In addition to troubling symptoms, some patients will have a more serious disease, which results in complications such as erosive esophagitis, dysphagia, Barrett esophagus, and esophageal carcinoma. Pulmonary complications may result from aspiration of stomach acid into the lungs and can include asthma, pulmonary fibrosis, and bronchitis, or symptoms of chronic hoarseness, cough, and sore throat.

Treatment
Guidelines on the management of GERD emphasize initial medical management. Weight loss, smoking cessation, head of the bed elevation, and elimination of food triggers are all recommended in recent practice guidelines.1, Proton pump inhibitors have been shown to be the most effective medical treatment. In a Cochrane systematic review, van Pinxteren et al (2010) reported that proton pump inhibitors demonstrated superiority to H2-receptor agonists and prokinetics in both network meta-analyses and direct comparisons.2,

Surgical Treatment
The most common surgical procedure used for GERD is laparoscopic Nissen fundoplication. Fundoplication involves wrapping a portion of the gastric fundus around the distal esophagus to increase lower esophageal sphincter pressure. If a hiatal hernia is present, the procedure also restores the position of the lower esophageal sphincter to the correct location. Laparoscopic fundoplication was introduced in 1991 and has been rapidly adopted because it avoids complications associated with an open procedure.

Although fundoplication results in a high proportion of patients reporting symptom relief, complications can occur, and sometimes require conversion to an open procedure. Patients who have relief of symptoms of GERD after fundoplication may have dysphagia or gas-bloat syndrome (excessive gastrointestinal gas).

Other Treatment Options
Due in part to the high prevalence of GERD, there has been interest in creating a minimally invasive transesophageal therapeutic alternative to open or laparoscopic fundoplication or chronic medical therapy. This type of procedure may be considered natural orifice transluminal surgery. Three types of procedures have been investigated.

  1. Transesophageal endoscopic gastroplasty (gastroplication, transoral incisionless fundoplication) can be performed as an outpatient procedure. During this procedure, the fundus of the stomach is folded and then held in place with staples or fasteners that are deployed by the device. The endoscopic procedure is designed to recreate a valve and barrier to reflux.
  2. Radiofrequency energy has been used to produce submucosal thermal lesions at the gastroesophageal junction. (This technique has also been referred to as the Stretta procedure.) Specifically, radiofrequency energy is applied through 4 electrodes inserted into the esophageal wall at multiple sites both above and below the squamocolumnar junction. The mechanism of action of the thermal lesions is not precisely known but may be related to ablation of the nerve pathways responsible for sphincter relaxation or may induce a tissue-tightening effect related to heat-induced collagen contraction and fibrosis.
  3. Submucosal injection or implantation of a prosthetic or bulking agent to enhance the volume of the lower esophageal sphincter has also been investigated.

One bulking agent, pyrolytic carbon-coated zirconium oxide spheres (Durasphere), is being evaluated. The Gatekeeper™ Reflux Repair System (Medtronic) uses a soft, pliable, expandable prosthesis made of a polyacrylonitrile-based hydrogel. The prosthesis is implanted into the esophageal submucosa, and with time, the prosthesis absorbs water and expands, creating bulk in the region of implantation. U.S. Food and Drug Administration (FDA) product code: DQX. Endoscopic submucosal implantation of polymethylmethacrylate beads into the lower esophageal folds has also been investigated.

The Agency for Healthcare Research and Quality published a systematic review of management strategies for GERD in 2005, which was updated by Ip et al (2011).3,4, The 2005 comparative effectiveness review evaluated studies on the EndoCinch Suturing System, Stretta, Enteryx, and the NDO Plicator.3, The 2011 update excluded Enteryx and the NDO Plicator, because they were no longer available in the United States, and added the EsophyX procedure (endoscopic fundoplication), which was commercialized after the 2005 review.4, The 2011 report concluded that, for the 3 available endoscopic procedures (EndoCinch, Stretta, EsophyX), effectiveness remained substantially uncertain for the long-term management of GERD. All procedures have been associated with complications, including dysphagia, infection/fever, and bloating, although bloating and dsyphagia are also adverse events of laparoscopic fundoplication.5, A review of endoscopic treatment of GERD by Hummel and Richards (2015) noted that EndoCinch is no longer manufactured.6,  

Regulatory Status  
In 2007, EsophyX® (EndoGastric Solutions, Redmond, WA) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process for full-thickness plication. In 2016, EsophyX® Z Device with SerosaFuse Fasteners was cleared for marketing (K160960) by FDA through the 510(k) process for use in transoral tissue approximation, full thickness plication, ligation in the gastrointestinal tract, narrowing the gastroesophageal junction, and reduction of hiatal hernia of 2 cm or less in patients with symptomatic chronic gastroesophageal reflux disease (GERD).3 FDA product code: ODE.

The Medigus SRS Endoscopic Stapling System (MUSE, Medigus) was cleared for marketing by FDA through the 510(k) process in 2012 (K120299) and 2014 (K132151). MUSE is intended for endoscopic placement of surgical staples in the soft tissue of the esophagus and stomach to create anterior partial fundoplication for treatment of symptomatic chronic GERD in patients who require and respond to pharmacologic therapy. FDA product code: ODE.

In 2000, the CSM Stretta® System was cleared for marketing by FDA through the 510(k) process for general use in the electrosurgical coagulation of tissue and is specifically intended for use in the treatment of GERD. Stretta® is currently manufactured by Mederi Therapeutics (Greenwich, CT). FDA product code: GEI.

Durasphere® is a bulking agent approved for treatment of urinary and fecal incontinence (see evidence review 7.01.19). Use of this product for esophageal reflux would be considered off-label use. The website of Carbon Medical Technologies states that Durasphere GR is an investigational device in the United States "intended to treat problems associated with GERD."

Related Policies
20180 Endoscopic Radiofrequency Ablation or Cryoablation for Barrett’s Esophagus
70119 Injectable Bulking Agents for the Treatment of Urinary and Fecal Incontinence
701137 Magnetic Esophageal Ring to Treat Gastroesophageal Reflux Disease (GERD)

Policy
Magnetic esophageal sphincter augmentation to treat gastroesophageal reflux disease is considered MEDICALLY NECESSARY when the following criteria are met:1
 

  • Patient has a history of severe GERD for ≥1 year with daily symptoms, AND
  • Patient has tried and failed optimal non-surgical management of symptoms, including lifestyle modification, weight loss (if indicated), and daily proton pump inhibitor use for ≥ 6 months, AND
  • Patient has proven gastroesophageal reflux by either endoscopy or ambulatory pH monitoring, AND
  • Patient has evidence of adequate peristalsis by manometry or barium esophagram, AND
  • None of the following contraindications are present:
    • Morbid obesity (BMI >35)
    • Suspected or known allergies to metals such as iron, nickel, titanium, or stainless steel
    • Grade C or D (LA classification) esophagitis
    • Scleroderma
    • Esophageal stricture or gross esophageal anatomic abnormalities
    • Suspected or confirmed esophageal or gastric cancer
    • Prior esophageal or gastric surgery or endoscopic intervention.

Transoral incisionless fundoplication (TIF) (i.e., EsophyX®) is considered MEDICALLY NECESSARY as a treatment of gastroesophageal reflux disease when the following criteria are met:1  

  • Patient has a history of severe GERD for ≥1 year with daily symptoms, AND
  • Patient has tried and failed optimal non-surgical management of symptoms, including lifestyle modification, weight loss (if indicated), and daily proton pump inhibitor use for ≥ 6 months, AND
  • Patient has proven gastroesophageal reflux by either endoscopy, ambulatory pH monitoring, or barium esophagram, AND
  • None of the following contraindications are present:
    • Hiatal hernia >2cm in axial height and >2cm in greatest transverse dimension
    • Morbid obesity (BMI >35)
    • Esophagitis grade C or D
    • Barrett's esophagus > 2 cm
    • Non-healing esophageal ulcer
    • Fixed esophageal stricture or narrowing
    • Portal hypertension and/or varices
    • Active gastro-duodenal ulcer disease
    • Gastric outlet obstruction or stenosis
    • Gastroparesis
    • Prior esophageal surgery
    • Scleroderma
    • Suspected or confirmed esophageal or gastric cancer.

Transesophageal radiofrequency to create submucosal thermal lesions of the gastroesophageal junction (i.e., the Stretta® procedure) is considered INVESTIGATIONAL as a treatment of gastroesophageal reflux disease.

Endoscopic submucosal implantation of a prosthesis or injection of a bulking agent (e.g., polymethylmethacrylate beads, zirconium oxide spheres) is INVESTIGATIONAL as a treatment of gastroesophageal reflux disease.

Policy Guidelines
There are specific CPT codes for transoral incisionless fundoplication and the radiofrequency procedure:

43210 Esophagogastroduodenoscopy, flexible, transoral; with esophagogastric fundoplasty, partial or complete, includes duodenoscopy when performed

43257: Esophagogastroduodenoscopy, flexible, transoral; with delivery of thermal energy to the muscle of lower esophageal sphincter and/or gastric cardia, for treatment of gastroesophageal reflux disease.

Endoscopic submucosal injection of a bulking agent would most likely be coded using 43201 (Esophagoscopy, flexible, transoral; with directed submucosal injection[s], any substance) or code 43236 (Esophagogastroduodenoscopy, flexible, transoral; with directed submucosal injection[s], any substance).

Endoscopic implantation of a prosthesis would most likely be coded using code 43212 (Esophagoscopy, flexible, transoral; with placement of endoscopic stent [includes pre- and postdilation and guide wire passage, when performed]), code 43266 (Esophagogastroduodenoscopy, flexible, transoral; with placement of endoscopic stent [includes pre- and postdilation and guide wire passage, when performed]), or code 43499 (unlisted procedure, esophagus).   

Benefit Application
BlueCard®/National Account Issues
Some state or federal mandates (e.g., FEP) prohibit Plans from denying FDA-approved technologies as investigational. In these instances, Plans may have to consider the coverage eligibility of U.S. Food and Drug Administration (FDA)-approved technologies on the basis of medical necessity alone.

Rationale 
This policy was based, in part, on a 2003 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment of transesophageal endoscopic treatments for gastroesophageal reflux disease (GERD) and a 2016 Evidence Street Assessment on transoral incisionless fundoplication.5 Since the 2003 Assessment, this policy has been updated periodically using the MEDLINE database. The most recent literature update was performed through September 25, 2018. This medical policy addresses procedures which are currently available for use in the United States.

Medical policies assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function---including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical uses of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Transoral Incisionless Fundoplication for Symptoms Uncontrolled by Poton Pump Inhibitors
Clinical Context and Test Purpose
The purpose of TIF (e.g., EsophyX) is to provide a treatment option that is an alternative to or an improvement on existing therapies in patients with GERD and hiatal hernias of 2 cm or less not controlled by proton pump inhibitors (PPIs).

The question addressed in this medical policy is: Does TIF using the EsophyX System improve the net health outcomes in individuals with GERD?

The following PICOTS were used to select literature to inform this review.

Patients
The relevant population of interest is individuals with GERD and a hiatal hernia of 2 cm or less uncontrolled by PPIs.

Interventions
The therapy being considered is TIF (eg, EsophyX).

Comparators
The following practice is currently being used to treat GERD: laparoscopic fundoplication.

Outcomes
The general outcomes of interest are symptoms, change in disease status, quality of life, mediation use, and treatment-related morbidity.

Timing
Follow-up at 3 years is of interest to monitor outcomes.

Setting
Patients with GERD and a hiatal hernia of 2 cm or less uncontrolled by PPIs are actively managed by gastroenterologists and primary care providers in an outpatient setting.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:  

  • To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
  • In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
  • To assess longer term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
  • Studies with duplicative or overlapping populations were excluded.

Systematic Reviews
McCarty et al (2018) published a systematic review of RCTs and nonrandomized studies that showed significant improvement in a number of clinical outcomes for patients treated with TIF.6 For example, 89% of TIF patients discontinued PPI therapy after the procedure, and the Gastroesophageal Reflux Disease Health-Related Quality of Life (GERD-HRQL) questionnaire, Gastroesophageal Reflux Symptom Score, and Reflux Symptom Index (RSI) measures showed significant improvement.

Richter et al (2018) published a network meta-analysis of RCTs comparing TIF orlaparoscopic Nissen fundoplication (LNF) with sham or PPIs.7 The meta-analysis was limited by low-quality studies (one did not report randomization method, others lacked data on allocation concealment, blinding of outcome assessors, or other aspects of study protocol). However, it should be noted that a reason behind the scarcity of direct comparisons between TIF and LNF is the discrepancy in populations requiring the respective treatments: consequently, TIF studies included patients with mild esophagitis and small hiatal hernias (<2 cm), while LNF studies included patients with Los Angeles grade A, B, C, or D esophagitis and all sizes of hiatal hernias.

Tables 1 and 2 summarize the characteristics and results of selected systematic reviews.

Table 1. Characteristics of Systematic Reviews 

Study

Dates

Trials

Participants

N (Range)

Design

Duration

McCarty et al (2018)6

2008-2016

32

Patients met standard criteria for the TIF procedurea

1475 (10-124)

5 RCTs, 21 prospective and 6 retrospective studies

NR

Richter et al (2018)7

NR

7

Patients had GERD, established by endoscopic results indicating erosive esophagitis and/or abnormal ambulatory esophageal pH monitoringb

 

2 RCTs (TIF vs PPI); 2 RCTs (TIF vs sham); 3 RCTs (LNF vs PPIs)

  •  TIF:  6-12 mo
  • LNF vs PPI: 1-5 y

GERD: gastroesophageal reflux disease; LNF: laparoscopic Nissen fundoplication; mo: month; NR: not reported; PPI: proton pump inhibitor; RCT: randomized controlled trial; TIF: transoral incisionless fundoplication; y: year.
Body mass index <35 kg/m2; hiatal hernia size ≤2 cm; grade A, B, or C esophagitis using the Los Angeles classification; no underlying esophageal motility disorder.
b DeMeester score >14.7 and/or percentage total time at a pH <4 of ≥4.0%.

Table 2. Results of Systematic Reviews 

Study

Complete PPI Cessation

GERD-HRQL Score

GERSS

RSI Score

Other Objective Measures

 

 

 

 

Esophageal Acid Exposure (% time with pH <4)

McCarty et al (2018)6

N

1407 (28 studies)

1236 (25 studies)

NR (6 studies)

NR (8 studies)

722 (15 studies)

% (95% CI)

89 (82 to 95)

       

MD (95% CI)

 

17.72 
(17.31 to 18.14)

23.78 
(22.96 to 24.60)

14.28 
(13.56 to 15.01)

3.43 
(2.98 to 3.88)

p

<0.001

<0.001

<0.001

<0.001

<0.001

I2 (p)

93.6 (0.00)

94 (<0.001)

98 (<0.001)

95 (<0.001)

86 (<0.001)

Mean follow-up (SD), mo

15.5 (14.6)

       

 

 

TIF-2 Subgroup

 

 

TIF-2 Subgroup

N

 

997 (15 studies)

 

 

 

MD (95% CI)

 

17.62 
(17.19 to 18.05)

 

 

53.18 
(49.49 to 56.87)

p

 

<0.001

 

 

<0.001

Richter et al (2018)7

N

 

  • TIF=293 (4 studies)
  • LNF=875 (3 studies)

 

 

 

OR (95% CrI)

 

TIF vs LNF: 2.08 
(0.71 to 6.09)

 

 

LNF vs TIF: 0.08 
(0.02 to 0.36)

Ranking probability (SUCRA)

 

  • TIF=0.96
  • LNF=0.66
  • Sham=0.35
  • PPI=0.042

 

 

  • LNF=0.99
  • PPI=0.64
  • TIF=0.32
  • Sham=0.05

CI: confidence interval; CrI: credible interval; GERD-HRQL: Gastroesophageal Reflux Disease Health-Related Quality of Life questionnaire; GERSS: Gastroesophageal Reflux Symptom Score; LNF: laparoscopic Nissen fundoplication; MD: mean difference; mo: month; NR: not reported; OR: odds ratio; PPI: proton pump inhibitor; RSI: Reflux Symptom Index; TIF: transoral incisionless fundoplication.

Randomized Controlled Trials
Two RCTS have evaluated TIF using EsophyX2 in patients with troublesome symptoms despite daily PPI therapy (see Table 3). Hunter et al (2015) compared treatment using TIF plus placebo pills (n=87) with treatment using sham TIF plus PPIs (n=42) in the RESPECT trial.8 Increases in medication (placebo or PPI depending on treatment group) were allowed at 2 weeks. At 3 months, patients with continued troublesome symptoms were declared early treatment failures, and failed TIF patients were given PPI and failed sham patients were offered TIF. Trad et al (2015) compared TIF (n=40) with maximum PPI therapy (n=23) without a sham procedure in the TEMPO trial.9 The primary outcome in both trials was the elimination of symptoms, measured in slightly different ways (see Table 3).

In both trials, the primary outcome was achieved by a higher percentage of patients treated with TIF than with PPIs (see Table 4). Elimination of symptoms was reported by 62% to 67% of patients treated by TIF compared with 5% of patients treated with maximum PPIs and 45% of patients who had a sham procedure plus PPIs (p=0.023). In TEMPO, the relative risk of achieving the primary outcome was 12.9 (95% confidence interval [CI], 1.9 to 88.9; p<0.001).

Secondary outcomes for the RESPECT trial showed no significant differences between treatments, except for Reflux Disease Questionnaire scores, which showed significant improvement in the TIF group compared with baseline. Physiologic measurements such as the number of reflux episodes, percentage of total time pH less than 4, and DeMeester score (a composite score of acid exposure based on esophageal monitoring) showed statistically significant differences between groups.

In TEMPO, self-reported troublesome regurgitation was eliminated in 97% (29/30) of TIF patients who were off PPIs. However, the objective measure of esophageal acid exposure did not differ significantly between groups.

Table 3. Characteristics of Randomized Controlled Trials Comparing TIF With Medical Management in Patients Whose Symptoms Were Not Controlled on PPIs

Study; Trial

TIF/CTL, n

Patient Symptoms or Other Characteristics

Comparator

FU, month

Principal Clinical Outcome

Hunter et al (2015)8

RESPECT

87/42

  • Hiatal hernia ≤2 cm
  • Troublesome regurgitationa not controlled on PPI

Sham + PPI

6

Relief of regurgitation without PPI in TIF group vs PPI escalation in control group

Trad et al (2015) 9

TEMPO

40/23

  • Hiatal hernia ≤2 cm
  • Troublesome symptoms not controlled on PPIb

Maximum-dose PPI

6

Elimination of daily symptoms other than heartburn

CTL: control; FU: follow-up; PPI: proton pump inhibitor; TIF: transoral incisionless fundoplication.

a Troublesome regurgitation was defined as mild symptoms for ≥2 days a week or moderate-to-severe symptoms >1 day a week
b Gastroesophageal reflux disease for >1 year and a history of daily PPI use for >6 months.

Table 4. Results for RCTs Comparing TIF With Medical Management in Patients Whose Symptoms Were Not Controlled on PPIs 

Trial

Symptoms

Regurgitation

Heartburn

Reflux

Esophageal pH

 

Elimination of Troublesome Regurgitation

Change in RDQ Regurgitation Score

Change in RDQ Heartburn Score

Change in RDQ Heartburn Plus Regurgitation Score

 

RESPECT (2015)8

TIF + placebo, % (n/N)

67% (58/87)

-3

-2.1

-2.5

 

Sham + PPI, % (n/N)

45% (19/42)

-3

-2.2

-2.4

 

p

0.023

0.072

0.936

0.313

 
 

Elimination of Symptoms Other Than Heartburnb

Change in GERD-HRQL Score

Change in GERD-HRQL Heartburn Score

RSI Score

Percent time With pH>4

TEMPO (2015)9

TIF

62%

-21.1

-14

-17.4

54%

Maximum-dose PPI

5%

-7.6

-5.2

-3.0

52%

RR (95% CI)

-12.9 (1.9-88.9)

       

p

0.001

NR

NR

NR

0.914

Summary

TIF

62%-67%

       

CI: confidence interval; GERD-HRQL: Gastroesophageal Reflux Disease Health-Related Quality of Life; NR: not reported; PPI: proton pump inhibitor; RCT: randomized controlled trial; RDQ: Reflux Disease Questionnaire; RR: relative risk; RSI: Reflux Symptom Index; TIF: transoral incisionless fundoplication.

a Primary outcome measure.
b Primary outcome measure acomposite of 3 GERD symptom scales: the GERD-HRQL, RSI, and RDQ.

Trad et al (2017) reported 3-year follow-up for patients treated with TIF in the TEMPO trial (see Table 5).10 All patients in the control group (maximum PPIs) had crossed over to TIF andwere included in the follow-up. Symptom scores, esophagastroduodenoscopy, and 48-hour pH monitoring were conducted off PPIs, and the 2 TIF failures who had undergone fundoplication were assigned the worst scores. Of 63 patients treated with TIF, data on PPI use was available for 52 (83%), with 71% of patients reporting a cessation of PPI use. However, completion of the Reflux Disease Questionnaire and assessment of pH normalization were available for 77% of patients. pH normalization was available for 40% of available patients following TIF, whereas 90% reported elimination of troublesome regurgitation.

Trad et al (2018) also reported 5-year follow-up for the TEMPO trial (see Table 5).11 Data were available for 44 patients, of whom 37 (86%) showed elimination of troublesome regurgitation at 5 years. Twenty (43%) patients were completely off PPIs at the 5-year follow-up, and 31 (70%) patients expressed satisfaction with the procedure, as assessed by the GERD-HRQL scores. While data on pH normalization were available for 24 patients at the 3-year follow-up, at 5 years, 22% (n=5) of these patients could not be assessed for pH normalization.

Table 5. Follow-Up of Patients Treated With EsophyX2 in the TEMPO Trial 

Outcome Measure

Baseline

1 Year

2 Years

3 Years

5 Years

Sample size (% of 63)

 

60 (95%)

55 (87%)

52 (83%)

44 (98%)

Elimination of troublesome regurgitation (RDQ)a

 

88% (42/48)

90% (41/44)

90% (37/41)

86% (37/43)

Elimination of atypical symptoms (RSI ≤13)a

 

82% (45/55)

84% (43/51)

88% (42/48)

80% (31/39)

GERD-HRQL Score

32.8 (60)

7.1 (/58)

7.3 (/52)

5.0 (/43)

6.8 (/31)

Esophagitis

55% (33/60)

5% (3/59)

10% (5/50)

12% (5/41)

 

Cessation of PPI use

 

78% (47/60)

76% (42/55)

71% (37/52)

46% (20/44)

pH normalizationb

 

41% (24/59)

37% (18/49)

40% (16/40)

 

Adapted from Tradet al (2017) and Trad et al (2018).10,11
Values are % (n/N) unless otherwise noted.
GERD-HRQL: Gastroesophageal Reflux Disease Health-Related Quality of Life; PPI: proton pump inhibitor; RDQ: Reflux Disease Questionnaire; RSI: Reflux Symptom Index.

a Primary outcome: elimination of daily troublesome regurgitation and atypical symptoms as measured with the RDQ and RSI. Troublesome symptoms are defined as mild symptoms, occurring ≥2 days a week, or moderate-to-severe symptoms, occurring >1 day a week.
b Normality was defined as percent of total recorded time pH <4 of ≥5.3%.

Nonrandomized Studies
Two nonrandomized comparative studies have compared TIF with laparoscopic fundoplication in patients whose symptoms were not controlled on PPIs.12,13

A nonrandomized study by Toomey et al (2014) compared 20 patients undergoing TIF, 20 patients undergoing Nissen fundoplication, and 20 patients undergoing Toupet fundoplication.12 Age, body mass index, and preoperative DeMeester score were controlled, however, the indications for each procedure differed. Patients with abnormal esophageal motility underwent Toupet fundoplication. Only patients who had a hiatal hernia of 2 cm or less were offered TIF. As a result, only 15% of the TIF group had a hiatal hernia versus 65% and 55% of the 2 fundoplication groups, limiting comparison of both treatments. Adverse events were not reported.

Frazzoni et al (2011) compared 10 patients undergoing TIF to 10 patients undergoing laparoscopic fundoplication with the first-generation EsophyX procedure.13 Patients selected which treatment they wanted, but the groups were comparable to a baseline. Regarding clinical outcomes assessed at 3 months, 7 patients undergoing TIF reported only partial/no symptom remission versus 0 patients undergoing fundoplication (p=0.003). Mild dysphagia was reported by 2 patients after fundoplication and 1 patient after TIF. Two patients reported epigastric bloating after fundoplication. Several measures of GERD as assessed by manometry and impedance pH monitoring showed greater improvement in the fundoplication group than in the TIF group. This study reported that TIF is less effective than fundoplication in improving symptoms of GERD. Adverse perioperative events were not described.

Tables 6 and 7 summarize the characteristics and results of selected nonrandomized studies.

Table 6. Nonrandomized Study Characteristics

Study

Study Type

Country

Dates

Participants

Treatment

Treatment

Follow-Up

Toomey et al (2014)12

Case control

U.S.

2010-2013

Patients with GERD undergoing TIF, LNF, or LTF

20 patients underwent TIF

20 patients each had LTF or LNF

NR

Frazzoni et al (2011)13

Prospective open-label

Italy

2000-2008

Patients had heartburn and/or regurgitation despite high-dose PPIs

10 patients chose first-generation EsophyX fundoplication

10 patients chose laparoscopic fundoplication

3 mo

GERD: gastroesophageal reflux disease; LNF: laparoscopic Nissen fundoplication; LTF: laparoscopic Toupet fundoplication; mo: month; NR: not reported; PPI: proton pump inhibitor; TIF: transoral incisionless fundoplication.

Table 7. Nonrandomized Study Results in Patients Whose Symptoms Were Not Controlled by PPIs 

Study

Percent Partial or No Symptom Remission

Normalization Esophageal Acid Exposure Time

Normalization of Distal Refluxes

Normalization of Proximal Refluxes

Mild Dysphagia

Bloating

Frazzoni et al (2011)13

TIF, %

70

50

20

40

10

0

Fundopli-cation, %

0

100

90

100

20

20

p

0.003

0.03

0.005

0.011

NR

NR

NR: not reported; PPI: proton pump inhibitor; TIF: transoral incisionless fundoplication.

TIF for Symptoms Controlled by PPIs
Clinical Context and Test Purpose
The purpose of TIF (e.g., EsophyX) is to provide a treatment option that is an alternative to or an improvement on existing therapies in patients with GERD and hiatal hernias of 2 cm or less controlled by PPIs.

The question addressed in this medical policy is: Does TIF using the EsophyX System improve the net health outcomes in individuals with GERD?

The following PICOTS were used to select literature to inform this policy.

Patients
The relevant population of interest is individuals with GERD and hiatal hernias of 2 cm or less controlled by PPIs.

Interventions
The therapy being considered is TIF (e.g., EsophyX).

Comparators
The following therapy is currently being used to treat GERD: PPI therapy.

Outcomes
The general outcomes of interest are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity.

Timing
Follow-up at 2, 3, and 6 years is of interest to monitor outcomes.

Setting
Patients with GERD and hiatal hernias of 2 cm or less controlled by PPIs are actively managed by gastroenterologists and primary care providers in an outpatient setting.

Study Selection Criteria
Methodologically credible studies were selected using the principles outlined in indication 1.

Randomized Trials
Two published RCTs have evaluated the efficacy of TIF in patients whose symptoms were adequately controlled on PPIs, but who were considering an intervention over lifelong drug dependence (see Table 8). Hakansson et al (2015) compared TIF (n=22) to sham only (n=22).14 The expected outcome in the sham group was that, without PPI, GERD symptoms would eventually recur. Witteman et al (2015) compared TIF (n=40) with continued PPI therapy (n=20) without a sham procedure (see Table 8).15 The objective was to demonstrate that outcomes with TIF were not significantly worse than those with continued PPI therapy.

The primary outcome of the Hakansson trial was treatment failure, defined as the need to resume PPIs. The primary outcome of the Witteman trial was treatment success, defined by an improvement of 50% or more on the GERD-HQRL score.

In Hakansson et al (2015), Kaplan-Meier curves showed a higher rate of treatment failure in the sham group than in the TIF group (p<0.001, time to treatment failure) with significantly more patients in the TIF group in remission at 6 months (59%) compared with the shame without PPI group (18%, p=0.01). In Witteman et al (2015), PPI therapy was stepped up or down as necessary during follow-up. At 6 months, 55% of TIF patients had more than 50% improvement in subjective GERD symptoms versus 5% of patients on continued PPI therapy (see Table 9). Mean change in GERD symptoms from baseline was consistent with this result (TIF, -14.1; control, -3.1).

Secondary outcomes measuring GERD symptoms in the Hakansson trial showed results consistent with more favorable outcomes in the TIF group. However, no statistical between-group analysiswas reportedfor these outcomes. Dysphagia, bloating, and flatulence were reported in twice as many patients undergoing TIF (4, 4, and 2, respectively) compared with sham (2, 2, and 1, respectively). These results were reported as not statistically different. However, it is unlikely that the trial was powered to detect differences in these outcomes.

Table 8. Characteristics of Randomized Trials Assessing TIF in Patients Whose Symptoms Were Controlled by PPIs 

Study

TIF/CTL, n

Patient Symptoms or Other Characteristics

Comparator

FU, mo

Principal Clinical Outcome

Hakansson et al (2015) (14)

22/22

Controlled on PPI, run-in to confirm PPI dependence

Sham only

≥6

Time to resumption of PPI, percent needing PPI at 6 mo

Witteman et al (2015) (15)

40/20

Controlled on PPI; those who received TIF had GERD with hiatal hernias ≤ 2 cm

Continued PPI only

6

Mean GERD symptoms, percent with >50% improvement

CTL: control; FU: follow-up; GERD: gastroesophageal reflux disease; mo: month; PPI: proton pump inhibitor; TIF: transoral incisionless fundoplication.

Table 9. Results of RCTs Comparing TIF With Nonsurgical Treatment in Patients Whose Symptoms Were Controlled on PPIs 

Study

Days to PPI Resumption

Change in PPI Therapy

Change in Symptoms

Change in QOL

Change in Esophagitis

Esophageal pH

   

Remission at 6 Months

Median GSRS Score

Median QOLRAD Score

 

Percent Time ph<4

Hakansson et al (2015)14

TIF

197

13 (59%)

4

1.4

 

3.6%

Sham only

107

4 (18%)

1.4

0.4

 

9.8%

p

0.001

0.01

NR

NR

 

NR

     

Percent >50% Improvement in GERD-HRQL Score

Mean GERD-HRQL Score

Percentage With Esophagitis

Percent Patients With Normalized pHa

Witteman et al (2015)15

TIF

   

55%

-14.1

-19%

50%

Continued PPI

   

5%

-3.1

-20%

63%

p

   

<0.001

<0.001

>0.05

NR

GERD-HRQL: Gastroesophageal Reflux Disease Health-Related Quality of Life; GSRS: Gastrointestinal Symptom Rating Scale; NR: not reported; PPI: proton pump inhibitor; QOL: quality of life; QOLRAD: Quality of Life in Reflux and Dyspepsia; RCT: randomized controlled trial; TIF: transoral incisionless fundoplication.

a Defined as <4% for ≤4.2% of recording time.

In the trial by Witteman et al (2015), 26% of TIF patients resumed at least occasional PPI use by 6 months, and 100% of control patients remained on PPI therapy. With the exception of LES resting pressure, physiologic and endoscopic outcome measures did not differ significantly between groups. No adverse events related to fundoplication were identified on the Symptom Rating Scale.

TIF patients were followed beyond 6 months, with additional control patients who crossed over to have TIF. Sixty patients eventually underwent TIF, but there were losses to follow-up at 6 (7 patients) and 12 months (additional 8 patients). Although GERD symptoms remained improved over baseline (p<0.05), esophageal acid exposure did not differ significantly from baseline. At least occasional use of PPI increased between 6 months and 12 months, from 34% to 61%. Endoscopy findings at 6 months and 12 months showed several findings indicating possible worsening of GERD in terms of esophagitis rating, Hill grade rating of the gastroesophageal valve, and size of hiatal hernia. Although this RCT met its principal end point at 6 months, and improvements in GERD symptoms appeared to be maintained to 12 months, long-term reflux control was not achieved.

Observational Studies
Observational case series and prospective cohort studies can provide information on the durability of the TIF procedure. Studies were included if they provided additional information on treatment durability or addressed treatment safety.

A case series and a cohort study have evaluated outcomes to 6 years after TIF 2 (see Tables 10 and 11). Both studies were performed in patients with hiatal hernias of 2 cm or less in size whose symptoms were adequately controlled on PPIs but did not want to take medication indefinitely. Stefanidis et al (2017) reported on a retrospective series that about 75% of patients had the elimination of esophagitis and had discontinued PPI use at 5 years, while 62% of the 13 patients with hiatal herniashad a reduction in hernia size at follow-up.16

In a prospective cohort by Testoni et al (2015), 72% of the patients were completely responsive to PPIs at baseline, and 24% were partially responsive.17 Hiatal hernias had recurred by 12 months in 46% of the patients who had hernias at baseline, and at the 24-month follow-up, 20% of TIF procedures were considered unsuccessful. Eight percent of patients had additional surgery for poor response by 2 years. The Johnson-DeMeester score was not significantly improved. A poor response to treatment was associated with a hiatal hernia of 2 cm, higher Hill grade, the presence of esophagitis at baseline, and use of fewer fasteners. About half the patients with a complete response initially resumed PPI use, although this finding is limited by the low number of patients followed to six years. The number of fasteners used in this study might also be lower than current procedures.

Table 10. Characteristics of Observational Studies With Long-Term Outcomes in Patients Whose Symptoms Were Controlled by PPIs 

Study

Country

Participants

Treatment Delivery

Mean FU, mo

Stefanidis et al (2017) 16

Greece

PPI—controlled, hiatal hernia ≤ 2 cm

EsophyX2

59

Testoni et al (2015)17

Prospective study from 1 center in Italy

Daily PPI, esophagitis or abnormal pH, hiatal hernia ≤ 2 cm

EsophyX2

53

FU: follow-up; mo: month; PPI: proton pump inhibitor.

Table 11. Long-Term Durability of TIF in Patients Whose Symptoms Were Controlled by PPIs 

Outcomes

Mean Baseline

6 Months

1 Year

2 Years

3 Years

6 Years

Stefanidis et al (2017)16

Sample size

45

       

44

GERD-HRQL score off PPI

27

       

4

PPI discontinuation

         

72.7%

Elimination of esophagitis

n=33

 

81.8%

   

72.7%

Reduction in hiatal hernia

n=13

       

61.5%

Testoni et al (2015)17

Sample size

50

49a

49

45b

32

14

GERD-HRQL score off PPI (SD)

46 (19)

   

16 (13)

17 (14)

 

GERD-QUAL score off PPI (SD)

114 (20)

   

71 (24)

80 (21)

 

Johnson-DeMeester score (SD)

22 (12)

18 (15)

 

19 (20)

   

PPI discontinuation

 

61.2%

51.0%

56.1%

53.1%

35.7%

Additional surgery for poor response

     

8.2%

   

GERD-HRQL: Gastroesophageal Reflux Disease Health-Related Quality of Life; GERD-QUAL: Gastroesophageal Reflux Disease Quality of Life; PPI: proton pump inhibitor; SD: standard deviation; TIF: transoral incisionless fundoplication.

a Excluding 1 failed procedure due to pneumothorax
b Excluding 4 patients who underwent Nissen fundoplication for failed procedure.

Adverse Events
Huang et al (2017) conducted a systematic review with meta-analysis of TIF for the treatment of GERD.18 They included 5 RCTs and 13 prospective observational studies, of which 14 were performed with the TIF 2 procedure. Efficacy results from the RCTs were combined for patients whose symptoms were controlled by PPIs and for those whose symptoms were not controlled by PPIs, and are not further discussed here. The follow-up to 6 years in prospective observational studies indicated a decrease in efficacy over time. The reported incidence of severe adverse events, consisting of gastrointestinal perforation and bleeding, was 19 (2.4%) of 781 patients. This included 7 perforations, 5 cases of post-TIF bleeding, 4 cases of pneumothorax, 1 case requiring intravenous antibiotics, and 1 case of severe epigastric pain.

Transesophageal Radiofrequency
Clinical Context and Test Purpose
The purpose of endoscopic radiofrequency energy (e.g., Stretta) is to provide a treatment option that is an alternative to or an improvement on existing therapies in patients with GERD.

The question addressed in this medical policy is: Does the use of endoscopic radiofrequency energy improve the net health outcomes in individuals with GERD?

The following PICOTS were used to select literature to inform this policy.

Patients
The relevant population of interest is individuals with GERD.

Interventions
The therapy being considered isendoscopic radiofrequency energy (e.g., Stretta).

Comparators
The following therapies and practices are currently being used to treat GERD: PPI therapy and laparoscopic fundoplication.

Outcomes
The general outcomes of interest are symptoms, change in disease status, quality of life,medicationuse, and treatment-related morbidity.

Timing
Follow-up at 3, 5, and 6 years is of interest to monitor outcomes.

Setting
Patients with GERD are actively managed by gastroenterologists and primary care providers in an outpatient setting.

Study Selection Criteria
Methodologically credible studies were selected using the principles outlined in indication 1.

Systematic Reviews
Fass et al (2017) published a meta-analysis of cohort studies and RCTs evaluating the Stretta procedure for patients with GERD.19 When RCT and cohort results were pooled, there were clinically significant treatment effects for several ofend points; however, the analysis was limited by the lack of control groups in many studies. Also, only 1 end point was shared between the four included RCTs.

A meta-analysis of 4 RCTS (total N=165 patients) was published by Lipka et al (2015) (see Table 12).20 Three trials compared Stretta with sham, and one compared Stretta with PPI therapy (see Table 13). Results of the individual sham-controlled trials were inconsistent, generally supporting some improvement in symptoms, but not in objective measures of esophageal acid exposure. For example, Corley et al (2003) reported improvements in heartburn symptoms, quality of life, and general physical quality of life in the active treatment group compared with the sham group, there were no significant differences in medication use or esophageal acid exposure.21 Aziz et al (2010) found statistically significant improvements in GERD-HRQL in all treatment groups.22 Arts et al (2012) reported that the symptom score and quality-of-life score for bodily pain improved, no changes were observed in PPI use, esophageal acid exposure, or lower esophageal sphincter pressure after RF.23 Pooled results of the meta-analysis showed no significant difference between Stretta and either sham treatment or PPI management for the measured outcomes, including the ability to discontinue PPIs therapy (see Table 14). The overall quality of evidence was considered to be very low with a high risk of bias, and the meta-analysis was limited by heterogeneity in the included studies, which might have been due to small sample sizes, differences in measures, and differences in follow-up times.

A meta-analysis by Perry et al (2012) included 20 studies.24 This review analyzed the within-subjects results following treatment only. The control groups of available clinical trials were not included for comparison. Significant improvements were reported for subjective heartburn scores, GERD-HRQL scores, and 36-Item Short-Form Health Survey Physical Component Summary scores. For the studies that measured esophageal pH, significant improvements were found in the Johnson-DeMeester score, the esophageal acid exposure time, and lower esophageal sphincter pressure. This meta-analysis was limited by the inclusion of lower quality studies and by its analysis of within-subject differences and not between-subjects differences, as reported in the RCTs.

Table 12. Meta-Analytic Characteristics of RCTs Assessing TERF 

Study

Dates

Trials

Participants

N (Range)

Design

Duration, months

Fass et al (2017)19

2002-2012

28

2468 (9-558)

2468 (9-558)

Meta-analysis of 4 RCTs, 23 cohort studies, and 1 registry

3-120

Lipka et al (2015)20

Inception to Feb 2014

4

165 (22-64)

165 (22-64)

Meta-analysis of RCTs

6-12

Perry et al (2012)24

1966-2010

20

1441 (7-558)

1441 (7-558)

Meta-analysis ofsinglearm of 2 RCTs and 18 case series

4-48

GERD: gastroesophageal reflux disease; PPI: proton pump inhibitor; RCT: randomized controlled trial; TERF: transesophageal radiofrequency.

Table 13. Characteristics of RCTs Assessing TERF 

Study

TERF/CTL, n

Patient Symptoms or Other Characteristics

Comparator

FU, months

Principal Clinical Outcome

Arts et al (2012)23

11/11

GERD at least partially controlled by PPIs and abnormal pH, hiatal hernia ≤3 cm

Sham with crossover at 3 mo

3

Composite reflux symptom score, esophageal pH, motility, and distensibility

Aziz et al (2010)22

12/12

GERD controlled by PPIs; patients randomized to single or double TERF or sham

Sham

12

GERD-HRQL score

Coron et al (2008)25

20/16

GERD symptoms controlled by PPIs and abnormal EAE

Continued PPI

6

Stopping or decreasing PPI use

Corley et al (2003)21

35/29

Abnormal EAE, symptoms at least partially controlled by PPIs, hiatal hernia ≤2 cm

Sham

6

Heartburn, QOL, PPI use, pH

CTL: control; EAE: esophageal acid exposure; FU: follow-up; GERD: gastroesophageal reflux disease; GERD-HRQL: Gastroesophageal Reflux Disease Health-related Quality of Life; PPI: proton pump inhibitor; QOL: quality of life; RCT: randomized controlled trial; TERF: transesophageal radiofrequency.

Table 14. Meta-Analytic Results 

Study

Heartburn

GERD-HRQL Score

SF-36 PCS Score

Acid Exposure Time (pH<4)

Other Objective Outcome Measures

 

Heartburn Score

     

DeMeester Score

Fass et al (2017)19

Patients (studies), n

637 (12)

507 (11)

 

364 (11)

407 (8)

Pooled RR (95% CI)

-0.53

(-1.97 to -1.09)

RCT: -14.56 (-16.63 to -12.48)

Cohort: -14.69 (-16.90 to -12.47)

 

-3.01

(-3.72 to -2.30)

-13.79

(-20.01 to -7.58)

MD (95% CI)

 

-14.60

(-16.48 to -12.73)

     

p

<0.001

<0.001

 

<0.001

<0.001

I2 (p)

Significant in all subgroups (p<0.001)

RCTs: NS

Cohort: 85% (<0.001)

 

Not significant in any subgroup

77%

 

Use of PPI Therapy

     

LES Basal Pressure

Patients (studies), n

1795 (23)

     

269 (9)

Baseline, n (%)

1743 (97.1)

     

+1.73 (-0.29 to 3.74)

Posttreatment, n (%)

850 (49)

       

Pooled RR (95% CI)

0.49 (0.40 to 0.60)

       

p

<0.001

     

0.09

I2 (p)

RCTs: NS

Cohort: 95% (<0.001)

       
 

Ability to Stop PPI Therapy

     

Mean LES Pressure

Lipka et al (2015)20

Patients (studies), n

118 (3)

88 (2)

 

153 (4)

110 (3)

MD (95% CI)_

RR=0.87 (0.75 to 1.00)

-5.24

(-12.95 to 2.46)

 

1.56%

(-2.56% to 5.69%)

0.32 mm Hg (-2.66 to 2.02 mm Hg)

p

0.06

0.18

 

0.46

0.79

I2 (p)

0%

96% (<0.001)

 

99% (<0.001)

96% (<0.001)

Range of N

24-51

22-64

 

22-64

 
 

Heartburn Score

     

Johnson-DeMeester Score

Perry et al (2012)24

Patients (studies), n

525 (9)

433 (9)

299 (6)

364 (11)

267 (7)

Mean follow-up, mo

24.1

19.8

9.5

11.9

13.1

Baseline (SE_)

3.55 (3.9)

26.11 (27.2)

36.45 (51.6)

10.29% (17.8%)

44.37 (93)

Posttreatment (SE)

1.19 (3.4)

9.25 (23.7)

46.12 (61.9)

6.51% (12.5%)

28.54 (33.4)

p

0.001

0.001

0.001

0.003

0.007

CI: confidence interval; GERD-HRQL: Gastroesophageal Reflux Disease Health-related Quality of Life; LES: lower esophageal sphincter; MD: mean difference; PCS: Physical Component Summary; RCT: randomized controlled trial; RR; relative risk; SE: standard error; SF-36: 36-Item Short-Form Health Survey.

Randomized Controlled Trials
Although not included in the meta-analyses tabulated in Table 12, Kalapala et al (2017) published interim results from a small RCT of 20 patients randomized to PPI plus Stretta or PPI alone, with 3 months of follow-up.26 While short-term outcomes such as GERD symptoms and cessation of PPIs appeared improved for the Stretta group, the study sample was small and power calculations were not conducted.

Controlled Trials Comparing TERF With Laparoscopic Fundoplication
Liang et al (2015) reported a prospective comparison of laparoscopic Toupet fundoplication with the Stretta procedure (see Table 15).27 Of the 165 patients treated, 125 (76%) completed the 3-year follow-up (65 fundoplication, 60 Stretta) and were included in the analysis. Although the 2 groups were comparable in symptoms at baseline, 9 patients in the Stretta group had revised treatment and were not included in the final symptom scores. A similar percentage of remaining patients in the 2 groups achieved complete PPI independence and had similar improvements in belching, hiccup, cough, and asthma. The Stretta procedure was less effective than laparoscopic fundoplication in improving symptoms of heartburn, regurgitation, and chest pain (See Table 16). Significantly more patients in the Stretta group underwent reoperation, while more patients in the fundoplication group complained of bloating, but these differences were not statistically significant. This study lacked randomization and, along with not reporting the TERF failures, had a high loss to follow-up. Also, while symptom scores were comparable at baseline, the study may have been subject to selection bias related to treatment choice, which affected baseline differences for other variables.

Table 15. Characteristics of Studies Comparing TERF With Laparoscopic Fundoplication 

Study

Study Type

Country

Dates

Participants

Treatment 1

Treatment 2

FU, y

Liang et al (2015)27

Comparative cohort

China

2011

165

TERF

Laparoscopic fundoplication

3

FU: follow-up; TERF: transesophageal radiofrequency, y: year.

Table 16. Results Comparing TERF With Laparoscopic Fundoplication 

Study

PPI Indepen-dence

Improvement in Heartburn Score

Improvement in Regurgitation Score

Improvement in Chest Pain Score

Reoperation

Bloating

Liang et al. (2015)27

TERF

68.3%

2.53

2.41

2.96

11.8%

0%

LF

72.3%

4.05

4.03

5.50

0%

6.2%

p

0.627

0.01

0.004

0.005

0.006

0.120

LF: laparoscopic fundoplication; PPI: proton pump inhibitor; TERF: transesophageal radiofrequency.

Long-term follow-up from case series and cohort studies can inform the durability of TERF. For example, 5- and 10-year follow-ups after TERF were reported in 2014 (see Table 17).28,29 Elimination of PPI use was similar for both studies at around 42% (see Table 18). Liang et al (2014) reported that symptoms of heartburn, regurgitation, chest pain, cough, and asthma were all decreased compared with baseline. Noar et al reported symptom improvement in 72% of patients and elimination of dysplasia in 85% of patients, but the interpretation of these findings is limited due to the 34% loss to follow-up in this study.

Table 17. Cohort Study and Case Series Characteristics 

Study

Country/Institution

Participants

Follow-Up, years

Loss to Follow-Up

Liang et al (2014)28

China

152 who failed PPI therapy

5

9%

Noar et al (2014)29

University of Pittsburgh

149 who failed PPI therapy

10

34% (7% deceased)

PPI: proton pump inhibitor.

Table 18. Cohort Study and Case Series Results at Follow-Up 

Study

Elimination of PPI Use

Symptom Improvement

Elimination of Dysplasia

Bloating

Liang et al (2014)28

42.8%

P<0.001 vs pretreatment

 

8.7%

Noar et al (2014)29

41%

72%

85%

 

PPI: proton pump inhibitor.

Esophageal Bulking Agents
Clinical Context and Test Purpose
The purpose of esophageal bulking agents is to provide a treatment option that is an alternative to or an improvement on existing therapies in patients with GERD.

The question addressed in this medical policy is: Does the use of esophageal bulking agents improve the net health outcomes in individuals with?

The following PICOTS were used to select literature to inform this policy.

Patients
The relevant population of interest is individuals with GERD.

Interventions
The therapy being considered is esophageal bulking agents.

Comparators
The following therapies and practices are currently being used to treat GERD: PPI therapy and laparoscopic fundoplication.

Outcomes
The general outcomes of interest are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity.

Timing
Though not completely standardized, follow-up for GERD symptoms would typically occur in the months to years after starting treatment.

Setting
Patients with GERD are actively managed by gastroenterologists and primary care providers in an outpatient setting.

Study Selection Criteria
Methodologically credible studies were selected using the principles outlined in indication 1.

Durasphere
The available evidence for Durasphere consists of a single case series. One open-label pilot study by Ganz et al (2009) assessed of 10 GERD patients injected Durasphere (Carbon Medical Technologies), a bulking agent approved for treatment of urinary and fecal incontinence, at the gastroesophageal junction.30 At 12 months, 7 patients (70%) discontinued all antacid medication completely. No erosion, ulceration, or sloughing of material was noted at any injection site.

Gatekeeper Reflux Repair System
The available evidence for Gatekeeper Reflux Repair system consists of a single RCT reported by Fockens et al (2010).31 In this industry-funded sham-controlled single-blind multicenter study randomized 118 patients into Gatekeeper (n=75) or sham (n=43) treatment. An additional 25 patients were treated as lead-ins during the initial training of investigators and included only in the safety analysis. The patients were implanted initially with 4 Gatekeeper prostheses. At 3 months, 44% of implanted patients received retreatment with up to 4 additional prostheses due to unsatisfactory symptom control. The primary safety end point was reduction in serious device- and procedure-related adverse device effects, compared with a surgical procedure composite complication rate of 15%. Four serious adverse events were reported (2 perforations, 1 pulmonary infiltrate related to a perforation, 1 severe chest pain). The primary efficacy end point was reduction in heartburn symptoms using the GERD-HRQL questionnaire. Planned interim analysis after 143 patients were enrolled found that heartburn symptoms and esophageal acid exposure had improved significantly in both the Gatekeeper and sham groups at 6 months, but there was no significant difference between the 2 groups. The study was terminated early due to a lack of efficacy.

Polymethylmethacrylate Beads
The available evidence for this device consists of a single case series. A case series by Feretis et al (2001) evaluated transesophageal submucosal implantation of polymethylmethacrylate beads in 10 patients with GERD who were either refractory to or dependent on PPIs.32 While a significant decrease in symptom scores was noted at posttreatment follow-up (time not specified), the small number of patients and lack of long-term follow-up preclude scientific analysis. No additional studies have been identified evaluating this treatment option.

Summary of Evidence
For individuals who have gastroesophageal reflux disease (GERD) and a hiatal hernia of 2 cm or less that is not controlled by proton pump inhibitors (PPIs) who receive transoral incisionless fundoplication (TIF) (e.g., EsophyX), the evidence includes 2 randomized controlled trials (RCTs) comparing TIF with PPI therapy, nonrandomized studies comparing TIF with fundoplication, and case series with longer term follow-up. Relevant outcomes are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity. The highest quality RCT (RESPECT) wassham-controlled that compared TIF with PPI therapy while the other RCT (TEMPO) compared TIF with maximum PPI therapy. Both trials found a significant benefit of TIF on the primary outcome measure in about 65% of patients. The evidence is considered sufficient to determine the effects of the technology on health outcomes.

For individuals who have GERD and a hiatal hernia of 2 cm or less that is controlled by PPIs who receive TIF (e.g., EsophyX), the evidence includes 2 RCTs and observational studies with longer term follow-up. Relevant outcomes are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity. A sham-controlled trial found that the time to resume PPI therapy was longer following TIF and the remission rate was higher. The evidence is considered sufficient to determine the effects of the technology on health outcomes.

For individuals who have GERD who receive endoscopic radiofrequency energy (e.g., Stretta), the evidence includes 4 small RCTs, a nonrandomized comparative study, and observational studies with longer term follow-up. Relevant outcomes are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity. The RCTs reported some improvements in symptoms and quality of life following treatment with radiofrequency energy compared with sham controls. However, objective measures of GERD and a meta-analysis of these studies found no significant improvements in outcomes, raising questions about the mechanism of the symptom relief. Symptom relief is reported to be lower than after fundoplication, and reoperations greater. Larger RCTs with longer follow-up, preferably compared with fundoplication, are needed to define the risks and benefits of this procedure better. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have GERD who receive esophageal bulking agents, the evidence includes an RCT and case series. Relevant outcomes are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity. The RCT for a single product was terminated early due to lack of efficacy, while other products have only case series to support use. High-quality data from large RCTs are needed to compare bulking procedures with both sham controls and with the currently accepted treatments for GERD (i.e., drug therapy, laparoscopic fundoplication). Well-designed trials should use standardized outcome measures to examine whether subjective improvement (e.g., discontinuation of medication therapy, GERD-HRQL scores) is supported by objective improvement (e.g., esophageal acid exposure). The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements
American Society for Gastrointestinal Endoscopy
The American Society for Gastrointestinal Endoscopy (2015) published guidelines on endoscopic procedures for GERD.33 In its review of the EsophyX and Stretta procedures, the Society noted some positive findings but discrepancies between subjective and objective outcome measures or a lack of objective outcome measures in reported trials, concluding that these techniques represent “potentially new therapeutic indications for GI endoscopy”, but that prospective trials using objective measures of GERD as the primary end point could be useful in defining the clinical role of these procedures.

American College of Gastroenterology
Updated guidelines released by the American College of Gastroenterology (2013) indicated the use of current endoscopic therapy or transoral incisionless fundoplication (TIF) could not be recommended as an alternative to medical or traditional surgical therapy (conditional recommendation, moderate level of evidence).1 The guidelines also cited limited data on small numbers of subjects and short duration of follow-up.

Society of American Gastrointestinal and Endoscopic Surgeons
The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES; 2017) updated its evidence-based guidelines on endoluminal treatments for GERD.34 SAGES gave a strong recommendation based on moderate quality evidence that TIF using EsophyX can be performed with an acceptable safety risk in selected patients. SAGES concluded that EsophyX results in better control of GERD symptoms than proton pump inhibitor (PPI) treatment in the short term (6 months) and leads to similar improvements in objective GERD measures compared with PPIs. TIF appears to lose effectiveness during longer term follow-up and is associated with moderate patient satisfaction scores. SAGES found no comparative, controlled trials between TIF and surgical fundoplication, but preliminary evidence suggested that surgical fundoplication can be used safely after TIF failure.

SAGES gave a strong recommendation based on moderate quality evidence that Stretta is safe for adults and significantly improves health-related quality of life score, heartburn scores, the incidence of esophagitis, and esophageal acid exposure in patients with GERD. Stretta was found more effective than PPI, but less so than fundoplication.

American Society of General Surgeons
The American Society of General Surgeons (ASGS; 2011) issued a position statement on transoral fundoplication in 2011 stating that “ASGS supports the use of transoral fundoplication by trained General Surgeons for the treatment of symptomatic chronic gastroesophageal reflux disease (GERD) in patients who fail to achieve satisfactory response to a standard dose of Proton Pump Inhibitor (PPI) therapy or for those who wish to avoid the need for a lifetime of medication dependence.35

American Gastroenterological Association
The American Gastroenterological Association (2016) issued a technology coverage statement on minimally invasive surgical options for GERD.36 Based on a literature review of 4 randomized controlled trials, a multicenter registry, and case series with longer term follow-up, the Association stated:

“…evidence is sufficient to demonstrate sustainable improvement in health outcomes, symptom relief, decrease in PPI utilization and improvement in esophageal pH with transoral fundoplication. The selection criteria for transoral fundoplication includes GERD patients with BMI [body mass index] ≤ 35, hiatal hernia ≤ 2 cm, esophagitis LA [Los Angeles classification] grade A or B, Barrett’s esophagus ≤ 2 cm, and absence of achalasia and esophageal ulcer. This option should be considered in patients not responding to PPI therapy (symptoms of regurgitation) who have documented objective evidence of GERD (pathologic acid exposure on pH testing (both off and on medication)) or esophagitis.”

The National Institute for Health and Care Excellence
The National Institute for Health and Care Excellence (NICE; 2013) updated its guidance on endoscopic radiofrequency treatment for GERD, concluding: “The evidence on the safety of endoscopic radiofrequency ablation for gastro-esophageal reflux disease is adequate in the short and medium term but there is uncertainty about longer-term outcomes. With regard to efficacy, there is evidence of symptomatic relief but objective evidence on reduction of reflux is inconclusive…”37 NICE noted “concern on the part of some specialists about the possibility that symptoms may improve as a result of denervation caused by the procedure; if that were the case then failure to recognize and treat reflux might lead to complications in the long term.”

NICE (2011) issued guidance on endoluminal gastroplication for GERD, concluding that “The evidence on endoluminal gastroplication for gastroesophageal reflux disease raises no major safety concerns. Evidence from a number of RCTs [randomized controlled trials] shows a degree of efficacy in terms of reduced medication requirement in the short term, but changes in other efficacy outcomes are inconsistent, and there is no good evidence of sustained improvement in esophageal pH measurements…”38

NICE (2004) issued guidance on bulking agents for GERD found that “Current evidence on the safety and efficacy of endoscopic injection of bulking agents for gastro-esophageal reflux disease does not appear adequate for this procedure to be used without special arrangements…”39

NICE (2016) removed guidance on endoscopic bulking agents/hydrogel implants from guidelines on treatment for “dyspepsia and gastro-esophageal reflux” becausethe product had been withdrawn by the manufacturer.

U.S. Preventive Services Task Force Recommendations
Not applicable.

Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this policy are listed in Table 19.

Table 19. Summary of Key Trials 

NCT Number

Trial Name

Planned Enrollment

Completion Date

Ongoing

NCT01118585a

Prospective Outcome Evaluation of Transoral Incisionless Fundoplication (TIF) for the Treatment of Gastroesophageal Reflux Disease (GERD): The TIF Registry Study

500

Dec 2017 (ongoing)

NCT01682265

Stretta in Reflux Uncontrolled by Intake of Inhibitors of Protons Pump (IPP)-The SIRUP Trial-Multicentric, Randomized, Double Blind, Prospective Study

60

May 2019

NCT02366169a

A Worldwide Post-Market Surveillance Registry to Assess the Medigus Ultrasonic Surgical Endostapler (MUSE™) System for the Treatment of GERD

200

Dec 2019

Unpublished

NCT02211105

Laparoscopic NissenFundoplication(LNF) Surgery Versus Transoral Incisionless Fundoplication(TIF): Anti- Reflux Treatment Registry

64

Apr 2017 (terminated)

NCT01110811a

A Randomized Controlled Trial Comparing Transoral Incisionless Fundoplication (TIF) UsingEsophyXWith Sham Procedure for the Treatment of PPI Dependent GERD: the TIF vs. Sham Study

60

Mar 2017 (unknown)

NCT: national clinical trial.

a Denotes industry-sponsored or cosponsored trial.

References: 

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  18. Toomey P, Teta A, Patel K, et al. Transoral incisionless fundoplication: is it as safe and efficacious as a Nissen or Toupet fundoplication? Am Surg. Sep 2014;80(9):860-867. PMID 25197871
  19. Frazzoni M, Conigliaro R, Manta R, et al. Reflux parameters as modified by EsophyX or laparoscopic fundoplication in refractory GERD. Aliment Pharmacol Ther. Jul 2011;34(1):67-75. PMID 21539587
  20. Stefanidis G, Viazis N, Kotsikoros N, et al. Long-term benefit of transoral incisionless fundoplication using the esophyx device for the management of gastroesophageal reflux disease responsive to medical therapy. Dis Esophagus. Feb 01 2017;30(3):1-8. PMID 27868281
  21. Testoni PA, Testoni S, Mazzoleni G, et al. Long-term efficacy of transoral incisionless fundoplication with Esophyx (Tif 2.0) and factors affecting outcomes in GERD patients followed for up to 6 years: a prospective single-center study. Surg Endosc. Sep 2015;29(9):2770-2780. PMID 25480624
  22. Huang X, Chen S, Zhao H, et al. Efficacy of transoral incisionless fundoplication (TIF) for the treatment of GERD: a systematic review with meta-analysis. Surg Endosc. Mar 2017;31(3):1032-1044. PMID 27495332
  23. Fass R, Cahn F, Scotti DJ, et al. Systematic review and meta-analysis of controlled and prospective cohort efficacy studies of endoscopic radiofrequency for treatment of gastroesophageal reflux disease. Surg Endosc. Dec 2017;31(12):4865-4882. PMID 28233093
  24. Lipka S, Kumar A, Richter JE. No evidence for efficacy of radiofrequency ablation for treatment of gastroesophageal reflux disease: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. Jun 2015;13(6):1058-1067 e1051. PMID 25459556
  25. Corley DA, Katz P, Wo JM, et al. Improvement of gastroesophageal reflux symptoms after radiofrequency energy: a randomized, sham-controlled trial. Gastroenterology. Sep 2003;125(3):668-676. PMID 12949712
  26. Aziz AM, El-Khayat HR, Sadek A, et al. A prospective randomized trial of sham, single-dose Stretta, and double-dose Stretta for the treatment of gastroesophageal reflux disease. Surg Endosc. Apr 2010;24(4):818-825. PMID 19730952
  27. Arts J, Bisschops R, Blondeau K, et al. A double-blind sham-controlled study of the effect of radiofrequency energy on symptoms and distensibility of the gastro-esophageal junction in GERD. Am J Gastroenterol. Feb 2012;107(2):222-230. PMID 22108449
  28. Perry KA, Banerjee A, Melvin WS. Radiofrequency energy delivery to the lower esophageal sphincter reduces esophageal acid exposure and improves GERD symptoms: a systematic review and meta-analysis. Surg Laparosc Endosc Percutan Tech. Aug 2012;22(4):283-288. PMID 22874675
  29. Coron E, Sebille V, Cadiot G, et al. Clinical trial: Radiofrequency energy delivery in proton pump inhibitor-dependent gastro-oesophageal reflux disease patients. Aliment Pharmacol Ther. Nov 1 2008;28(9):1147-1158. PMID 18616516
  30. Kalapala R, Shah H, Nabi Z, et al. Treatment of gastroesophageal reflux disease using radiofrequency ablation (Stretta procedure): An interim analysis of a randomized trial. Indian J Gastroenterol. Sep 2017;36(5):337-342. PMID 29030802
  31. Liang WT, Yan C, Wang ZG, et al. Early and midterm outcome after laparoscopic fundoplication and a minimally invasive endoscopic procedure in patients with gastroesophageal reflux disease: a prospective observational study. J Laparoendosc Adv Surg Tech A. Aug 2015;25(8):657-661. PMID 26258269
  32. Liang WT, Wang ZG, Wang F, et al. Long-term outcomes of patients with refractory gastroesophageal reflux disease following a minimally invasive endoscopic procedure: a prospective observational study. BMC Gastroenterol. Oct 10 2014;14:178. PMID 25304252
  33. Noar M, Squires P, Noar E, et al. Long-term maintenance effect of radiofrequency energy delivery for refractory GERD: a decade later. Surg Endosc. Aug 2014;28(8):2323-2333. PMID 24562599
  34. Ganz RA, Fallon E, Wittchow T, et al. A new injectable agent for the treatment of GERD: results of the Durasphere pilot trial. Gastrointest Endosc. Feb 2009;69(2):318-323. PMID 19185691
  35. Fockens P, Cohen L, Edmundowicz SA, et al. Prospective randomized controlled trial of an injectable esophageal prosthesis versus a sham procedure for endoscopic treatment of gastroesophageal reflux disease. Surg Endosc. Jun 2010;24(6):1387-1397. PMID 20198491
  36. Feretis C, Benakis P, Dimopoulos C, et al. Endoscopic implantation of Plexiglas (PMMA) microspheres for the treatment of GERD. Gastrointest Endosc. Apr 2001;53(4):423-426. PMID 11275880
  37. ASGE Standards of Practice Committee, Muthusamy VR, Lightdale JR, et al. The role of endoscopy in the management of GERD. Gastrointest Endosc. Apr 2015;81(6):1305-1310. PMID 25863867
  38. Society of American Gastrointestinal and Endoscopic Surgeons. Clinical Spotlight Review: Endoluminal Treatments for Gastroesophageal Reflux Disease (GERD). 2017; https://www.sages.org/publications/guidelines/endoluminal-treatments-for-gastroesophageal-reflux-disease-gerd/. Accessed October 29, 2018.
  39. American Society of General Surgeons (ASGS). Coverage of Transoral fundoplication. 2011; https://theasgs.org/position-statements/coverage-of-transoral-fundoplication-2/. Accessed October 29, 2018.
  40. American Gastroenterological Association. Technology Coverage Statement on Minimally Invasive Surgical Options for Gastroesophageal Reflux Disease. 2016; https://www.gastro.org/about/Technology_Coverage_Minimally_Invasive_GERD_Procedures.pdf. Accessed October 29, 2018.
  41. National Institute for Health and Care Excellence (NICE). Endoscopic radiofrequency ablation for gastro-oesophageal reflux disease [IPG461]. 2013; https://www.nice.org.uk/guidance/ipg461. Accessed October 29, 2018.
  42. National Institute for Health and Care Excellence (NICE). Endoluminal gastroplication for gastro-oesophageal reflux disease [IPG404]. 2011; https://www.nice.org.uk/guidance/ipg404. Accessed October 25, 2017.
  43. National Institute for Health and Care Excellence (NICE). Endoscopic injection of bulking agents for gastro-oesophageal reflux disease [IPG55]. 2004; https://www.nice.org.uk/guidance/ipg55. Accessed October 29, 2018.
  44. Warren HF, Reynolds JL, Lipham JC, et al. Multi-institutional outcomes using magnetic sphincter augmentation versus Nissen fundoplication for chronic gastroesophageal reflux disease. Surg Endosc. Aug 2016;30(8):3289- 3296. PMID 26541740
  45. Asti E, Bonitta G, Lovece A, et al. Longitudinal comparison of quality of life in patients undergoing laparoscopic Toupet fundoplication versus magnetic sphincter augmentation: Observational cohort study with propensity score analysis. Medicine (Baltimore). Jul 2016;95(30):e4366. PMID 27472725
  46.  Reynolds JL, Zehetner J, Wu P, et al. Laparoscopic magnetic sphincter augmentation vs laparoscopic nissen fundoplication: a matched-pair analysis of 100 patients. J Am Coll Surg. Jul 2015;221(1):123- 128. PMID 26095560
  47. Riegler M, Schoppman SF, Bonavina L, et al. Magnetic sphincter augmentation and fundoplication for GERD in clinical practice: one-year results of a multicenter, prospective observational study. Surg Endosc. May 2015;29(5):1123-1129. PMID 25171881
  48. Louie BE, Farivar AS, Shultz D, et al. Short-term outcomes using magnetic sphincter augmentation versus Nissen fundoplication for medically resistant gastroesophageal reflux disease. Ann Thorac Surg. Jun 21 2014;98(2):498-504. PMID 24961840
  49. Sheu EG, Nau P, Nath B, et al. A comparative trial of laparoscopic magnetic sphincter augmentation and Nissen fundoplication. Surg Endosc. Jul 11 2014;29(3):505-509. PMID 25012804
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  54. Saino G, Bonavina L, Lipham JC, et al. Magnetic sphincter augmentation for gastroesophageal reflux at 5 years: final results of a pilot study show long-term acid reduction and symptom improvement. J Laparoendosc Adv Surg Tech A. Oct 2015;25(10):787-792. PMID 26437027
  55. Ganz RA, Edmundowicz SA, Taiganides PA, et al. Long-term outcomes of patients receiving a magnetic sphincter augmentation device for gastroesophageal reflux. Clin Gastroenterol Hepatol. May 2016;14(5):671- 677. PMID 26044316
  56. Lipham JC, Taiganides PA, Louie BE, et al. Safety analysis of first 1000 patients treated with magnetic sphincter augmentation for gastroesophageal reflux disease. Dis Esophagus. Mar 11 2015;28(4):305-311. PMID 24612509
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Coding Section

Codes

Number

Description

CPT  43201 

Esophagoscopy, flexible, transoral; with directed submucosal injection(s), any substance 

  43210 

Esophagogastroduodenoscopy, flexible, transoral; with esophagogastric fundoplasty, partial or complete, includes duodenoscopy when performed (new code 01/01/16) 

  43212

Esophagoscopy, flexible, transoral; with placement of endoscopic stent (includes pre- and dilation and guide wire passage, when performed) 

  43236 

Esophagogastroduodenoscopy, flexible, transoral; with directed submucosal injection(s), any substance 

  43257 

Esophagogastroduodenoscopy, flexible, transoral; with delivery of thermal energy to the muscle of lower esophageal sphincter and/or gastric cardia, for treatment of gastroesophageal reflux disease 

  43266 

Esophagogastroduodenoscopy, flexible, transoral; with placement of endoscopic stent (includes pre- and dilation and guide wire passage, when performed)

  43284 

Laparoscopy, surgical, esophageal sphincter augmentation procedure, placement of sphincter augmentation device (ie, magnetic band), including cruroplasty when performed

  43499

Unlisted procedure, esophagus 

HCPCS  C9724 

Endoscopic full-thickness plication of the stomach using endoscopic plication system (EPS); includes endoscopy

ICD-9 Procedure  44.66  Other procedure for creation of esophagogastric sphincteric competence (used for endoscopic suturing of the esophagogastric junction)  
ICD-9 Diagnosis  530.10-530.19  Esophagitis, code range 
ICD-10-CM (effective 10/1/15)    Investigational for all diagnoses 
  K21.0, K21.9  Gastro-esophageal reflux disease code list 
ICD-10-PCS (effective 10/1/15)  0DQ48ZZ  Repair, gastrointestinal system, esophagogastric junction, via natural or artificial opening, endoscopic  
  0DU48JZ  Supplement, gastrointestinal system, esophagogastric junction, via natural or artificial opening, endoscopic, synthetic substitute  
  0DV48DZ  Restriction, gastrointestinal system, esophagogastric junction, via natural or artificial opening, endoscopic, intraluminal device  
Type of Service  Medicine   
Place of Service     

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2014 Forward     

12/06/2019 

Interim review with updated policy statements including medical necessity criteria for magnetic esophageal sphincter augmentation and transoral incisionless fundoplication. Updating description, rationale and references. 

09/03/2019 

Annual review, no change to policy intent. Updating background, guidelines, rationale and references. 

09/04/2018 

Annual review, no change to policy intent. Updating description, rationale and references. 

09/12/2017

Annual review, no change to policy intent. Updating background, description, regulatory status, rationale and references. 

09/01/2016 

Annual review, no change to policy intent. Updating background, description, regulatory status, guidelines, rationale, coding and references. 

09/14/2015 

Annual review, no change to policy intent. Updated background, description, rationale, references and coding. Added guidelines and regulatory status.

09/18/2014

Annual review. Updated background/description, rationale & references. Added benefit application & ICD 9 & 10. No change to policy intent.


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