Coverage Policy Manual
Policy #: 2015015
Category: Surgery
Initiated: May 2015
Last Review: May 2018
  Vagal Nerve Blocking Therapy for the Treatment of Obesity

Description:
Obesity is a common condition in the United States. A large nationally representative survey conducted in 2009 to 2010 found that 35% of American adults age 20 and older were obese, defined as body mass index (BMI) of 30 kg/m2 or more.1 Fifteen percent of adults had a BMI of 35 kg/m2 or more and 6% had a BMI of 40 kg/m2 or more. Among children age 2 to 19 years, 16.9% were obese, defined in the pediatric population as 95% percentile or more in BMI for age.
 
Obesity is a major cause of premature death and is linked to serious illnesses including heart disease, type 2 diabetes, sleep apnea, osteoarthritis, and certain types of cancer. In meta-analyses, being obese has been associated with higher all-cause mortality and death from cardiovascular disease.2 In 2013, the American Medical Association officially recognized obesity itself as a disease.
 
Lifestyle interventions, specifically changes to diet and exercise, are the first-line treatment of obesity. These interventions can be enhanced by participation in a structured weight loss program and/or by psychological interventions such as cognitive behavioral therapy. There are also prescription weight loss medications, most notably orlistat (which blocks digestion and absorption of fat) and lorcaserin (which decreases appetite and promotes satiety). Weight loss medications have limited evidence of efficacy and there are associated adverse effects, eg, oily stool, nausea, and dizziness.
 
Weight loss (bariatric) surgery is a potential option for obese patients who have failed conservative treatments. Common procedures include gastric bypass surgery (open or laparoscopic approaches), sleeve gastrectomy, and laparoscopic adjustable gastric banding. Certain types of bariatric surgery have been found to improve outcomes in selected patients who choose that treatment.
 
Vagal nerve blocking therapy is another potential treatment option for obese patients. The vagus nerve consists of 2 long cranial nerves that extend from the brain stem to the viscera. The term vagus is Latin for wandering and the vagus nerve winds through the abdomen and has branches that come in contact with the heart, lung, stomach and other body parts. The vagus nerve plays a major role in autonomic and sympathetic nervous systems including regulation of heartbeat and breathing. It is also involved in regulation of the digestive system, although its exact role in controlling appetite and feelings of satiety is unknown. Vagal nerve blocking therapy involves intermittent blocking of signals to the intra-abdominal vagus nerve, with the intent disrupting hunger sensations and inducing feelings of satiety.
 
In 2014, FDA approved a medical device specifically designed to provide vagal nerve blocking therapy for weight regulation in obese patients. This device, the Maestro® Rechargeable System, includes a pulse generator that is implanted subcutaneously on the thoracic sidewall, and flexible leads approximately 47 cm in length that are placed on the abdominal anterior and posterior vagal nerve trunks. External components include a mobile charger, transmit coils, a programmable microprocessor and customized software. The system delivers high-frequency pulses of current to vagal nerve trunks; therapy parameters and the treatment schedule can be customized by a clinician. Like other surgical interventions, there is the potential for adverse effects. In addition, there may be other unintended consequences of disrupting signals to a particular portion of the vagus nerve.
 
(Stimulation of the vagus nerve via a device implanted within the carotid artery sheath has also been evaluated as a treatment for obesity and is addressed in Policy No. 2009044. Vagus nerve stimulation is FDA-approved to treat epilepsy and depression, not for obesity treatment.)
 
Regulatory Status
FDA approved the Maestro Rechargeable System, (Enteromedics, St. Paul, MN) through the premarket approval process on January 14, 2015. The device is indicated for use in adults age 18 years and older who have a BMI of 40 to 45 kg/m2 or a BMI of 35 to 39.9 kg/m2 with 1 or more obesity-related comorbidities and have failed at least 1 supervised weight management program within the past 5 years. Implantable components are incompatible with magnetic resonance imaging (MRI). In addition to need for MRI, contraindications to use of the device include conditions such as cirrhosis of the liver, portal hypertension and clinically significant hiatal hernia and the presence of a previously implanted medical device. FDA product code: PIM.
 
Coding
There are specific CPT category III codes for this therapy:
 
0312T Vagus nerve blocking therapy (morbid obesity); laparoscopic implantation of neurostimulator electrode array, anterior and posterior vagal trunks adjacent to esophagogastric junction (EGJ), with implantation of pulse generator, includes programming
0313T laparoscopic revision or replacement of vagal trunk neurostimulator electrode array, including connection to existing pulse generator
0314T laparoscopic removal of vagal trunk neurostimulator electrode array and pulse generator
0315T removal of pulse generator
0316T replacement of pulse generator
0317T neurostimulator pulse generator electronic analysis, includes reprogramming when performed
 

Policy/
Coverage:
Intra-abdominal vagal nerve blocking therapy in all situations, including but not limited to the treatment of obesity, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, Intra-abdominal vagal nerve blocking therapy is considered investigational in all situations, including but not limited to the treatment of obesity. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 

Rationale:
Assessment of efficacy for therapeutic intervention involves a determination of whether the intervention improves health outcomes compared with available alternatives. The optimal study design for this purpose is a randomized controlled trial (RCT) that compares the therapeutic intervention with existing alternative treatments and includes clinically relevant measures of health outcomes. Intermediate outcome measures, also known as surrogate outcome measures, may also be adequate if there is an established link between the intermediate outcome and true health outcomes. Nonrandomized comparative studies and uncontrolled studies can sometimes provide useful information on health outcomes but are prone to biases such as non-comparability of treatment groups, placebo effect, and variable natural history of the condition.
 
In the case of interventions to treat obesity, a double-blind RCT is optimal because these interventions require changes to patient behavior (diet and exercise) which are subject to the placebo effect. Health outcomes such as mortality, cardiovascular events, and rates of type 2 diabetes would be optimal, but are difficult to use as study end points due to the need for a large sample size and long follow-up period. Cardiovascular risk factors, such as changes in blood pressure, glucose, and lipid levels, are good intermediate measures because they have been linked with these health outcomes, and would require smaller sample sizes. Weight loss outcomes, reported as absolute change in weight or body mass index (BMI), or as percent excess weight loss (EWL) or percent BMI are acceptable intermediate outcome measures and are commonly used in obesity studies. Weight loss has been linked to improvements in cardiovascular risk factors. While there is no generally accepted threshold of percent EWL that is considered clinically significant, bariatric surgery trials generally define clinical success as loss of at least 50% EWL. The amount of weight loss is expected to be lower for other, less dramatic weight loss interventions.
 
Sham controls are useful for establishing the efficacy of an intervention beyond the placebo effect and for controlling for other nonspecific effects of interventions such as natural history, regression to the mean, etc. Because there are so many existing treatment options for weight loss, if sham-controlled weight loss intervention studies are positive, trials using an active comparator, such as medication or other types of surgery, are desirable.
 
Review of Evidence
The published literature on vagal nerve blockade for obesity consists of 2 RCTs, both of which were industry-sponsored, multicenter, double-blind and sham controlled (Sarr, 2012; Ikramuddin, 2014). Although both trials included a sham treatment group, protocols differed. In the 2012 EMPOWER trial, all participants had devices implanted and leads placed (Sarr, 2012). However, external controllers were programmed differently such that if the controllers were worn for 10 hours per day, the total charge delivered was 3.9 Coulombs (C) to patients in the treatment group and a negligible amount, 0.0014 C, to the sham group. In the 2014 ReCharge trial, all participants had devices implanted but no leads were placed in the sham group (Ikramuddin, 2014).
 
The primary efficacy outcomes were not met in either of the 2 RCTs. The difference in mean percent EWL was the sole primary efficacy outcome in the EMPOWER study and a co-primary outcome in the ReCharge study. This outcome was evaluated in both trials using a superiority margin of 10%, ie, the efficacy objective would only be met if there was more than a 10% difference between groups in EWL. U.S. Food and Drug Administration (FDA) documents state that the 10% margin, which was not attained in either trial, was considered to indicate a clinically meaningful difference in weight loss between active and sham treatment groups (SSED, 2015).
 
For the ReCharge trial, however, in addition to the primary efficacy analysis, the authors also conducted a post hoc analysis that evaluated the difference in EWL between groups using a 2-sided t test with no superiority margin. In this post hoc analysis, the difference between groups, 8.5% EWL was statistically significant. (The difference between groups in percent EWL in the EMPOWER study was only 1%.)
 
The outcome used in these studies was percent EWL and modest changes in this outcome may translate to a relatively small amount of weight loss relative to total weight for patients with morbid obesity. Mean initial body weight in the ReCharge trial was 249 pounds in the active treatment group and 255 pounds in the sham group. Mean excess body weight was 97 pounds in the treatment group and 99 pounds in the sham group. Thus, a difference of 10% EWL, used in the primary analyses, represents only about a 10 pounds difference in absolute weight loss and a 4% difference in absolute body weight.
 
The ReCharge study had a second primary outcome which was met if at least 55% patients in the active treatment group achieved at least 20% EWL and at least 45% achieved at least 25% EWL. This outcome was not achieved; the data showed that 52% of patients in the active treatment group achieved at least 20% EWL and 38% achieved at least 25% EWL. In the EMPOWER study, groups did not differ significantly on the secondary outcome measure, percent of patients achieving at least 25% EWL. In a post hoc subgroup analysis of the EMPOWER trial, longer duration of device use per day was related to a larger percentage of EWL. This association, however, occurred in the sham group, as well as the active treatment group. For example, EWL among patients who used the device fewer than 6 hours was 5% in the active treatment group and 6% in the sham group whereas EWL among patients who used the device at least 12 h/d was 30% and 22%, respectively. This finding suggests a substantial placebo effect associated with device use.
 
Both trials met their primary safety end points which related to SAEs. However, there were nonserious adverse events that occurred frequently.
 
Additional information on ReCharge trial design and findings was reported in FDA documents (SSED, 2015). The study was designed to evaluate primary end points at 12 months and then to continue following patients until 5 years post-implant. Patients were blinded until 12 months and unblinding began once all patients had completed the 12-month follow-up. After the 12-month follow-up, sham patients had the option of crossing over into the active treatment group.
 
At 18 months, follow-up data were reported for 117 patients (72%) initially assigned to the active treatment group and 42 (55%) assigned to the sham treatment group. The number of patients in the sham group who crossed over to active treatment and the timing of unblinding were not reported. At 18 months, the mean percent EWL was 25.3% in the active treatment group and 11.7% in the sham group. There was a mean between-group difference of 13.5% (95% confidence interval, 5.7% to 21.3%). In this analysis, the treatment group sustained the weight loss they achieved at 12 months, and the control group gained weight. However, there are several ways the 18-month analysis may be biased. Sham patients were unblinded starting at 12 months and unblinding could impact patient beliefs, perceptions and behaviors. For example, during the 12-month sham intervention phase of the trial, patients in both groups experienced decreased hunger, increased cognitive restraint and decreased food intake. Although not reported, it is likely that unblinding could have an impact on these factors which contributed to weight loss in the sham group during the first 12 months. Thus, due to potential biases associated with unblinding and crossover, conclusions cannot be drawn about the efficacy of vagal nerve blocking on maintenance of weight loss relative to a sham intervention. Finally, nearly half of the patients initially randomized to the sham group were not included in the 18-month analysis, which limits ability to draw conclusions about these data.
 
FDA documents also report longer term safety data. Analyses of data up to 48 months from the EMPOWER trial and 18 month data from the ReCharge trial did not identify any deaths or unanticipated SAEs. There were 13 surgical explants though 12 months (5 in active treatment group, 8 in sham group) and an additional 16 explants between 12 and 18 months (14 in active treatment group, 7 in sham group). Reasons for explant included patient decision, pain and need for magnetic resonance imaging.
 
An FDA advisory panel voted that the ReCharge trial demonstrated safety of the Maestro device but did not demonstrate efficacy because the 2 primary end points were not met. However, the panel noted the post hoc analysis finding a statistically significant improvement in weight loss between the two groups, an 8.5% difference, when the 10% superiority margin was not used. (In its conclusions, the panel did not mention the smaller 1% between-group difference in percent EWL in the EMPOWER trial.) The panel also considered the 18-month data from the ReCharge trial. In addition, the panel considered that there are currently limited options available for treatment of morbid obesity, and there is a need for additional therapies. The panel concluded that the benefits of the device outweigh the risks in patients who meet the criteria specified in the proposed indication.
 
Summary of Evidence
The evidence does not support the hypothesis that vagus nerve blocking treatment leads to clinically meaningful weight loss that improves health outcomes. The evidence base for vagal nerve blocking therapy consists of 2 randomized controlled trials (RCTs) comparing active with sham treatment for 12 months. The primary efficacy outcomes were not met for either trial. In both trials, at least a 10% difference between groups in excess weight loss (EWL) was a primary outcome.
 
In the more recent trial a post hoc analysis found that the observed difference in EWL between groups, 8.5%, was statistically significant. However, this degree of difference in EWL may not be clinically significant, as it represents an absolute difference in weight loss of approximately 8.5 pounds. In the first trial, the observed difference in EWL between groups was 1%. Unblinding occurred after 12 months and longer term comparative data are subject to potential biases. The 2 RCTs found that vagal nerve blocking was reasonably safe in terms of the rate of serious adverse events during follow-up. However, a substantial number of mild and moderate adverse events were reported. Due to the lack of evidence that the net health outcome is improved, vagal nerve blocking therapy does not meet primary coverage criteria and is considered investigational.
 
Practice Guidelines and Position Statements
No guidelines or position statements were identified that addressed vagal nerve blockade therapy for obesity were identified.
 
U.S. Preventive Services Task Force Recommendations
The U.S. Preventive Services Task Force (USPSTF) published recommendations for screening and management of obesity in adults in 2012 (USPSTF, 2012). USPSTF recommends screening all adults for obesity and referring those with a BMI of 30 kg/m2 or higher to intensive, multicomponent behavioral interventions. Vagal nerve blocking therapy and other surgical interventions were not addressed in the recommendations or literature review.
 
2016 Update
A literature search conducted through February 2016 did not reveal any new information that would prompt a change in the coverage statement.
 
Eighteen-month follow-up data from the ReCharge trial were published in the peer-reviewed literature by Shikora and colleagues (Shikora, 2015). The authors reported on a larger proportion of the patient population than discussed in FDA documents. In addition to the 159 (67%) of 239 randomized patients who completed the 18-month follow-up, the analysis also included 30 patients who missed the 18-month analysis but had a visit at 16 or 17 months. The additional patients included 11 from the active treatment group and 18 from the sham group, for a total sample size of 189 (79%). In the 2015 analysis, at 18 months, the mean percent EWL was 23.5% (95% CI: 20.8% to 26.3%) in the active treatment group and 10.2% (95% CI: 6.0% to 14.4%) in the control group. There was a mean between-group difference of 13.4% (8.4% to 18.4%). The authors also evaluated the potential impact of blinding and found no statistically significant impact of blinding on their findings; findings were also similar when the analysis was restricted to patients who remained blinded at 18 months. The degree of EWL at 18 months in this analysis of ReCharge trial data are similar to those previously published in FDA documents although sample size is larger, limiting potential bias from missing data. However, this was a post hoc analysis which incorporates 16- and 17- month data in addition to 18-month data and results are considered preliminary or hypothesis-generating. Long-term findings need to be replicated in additional appropriately-designed RCTs.
 
Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in January 2016 did not identify any ongoing or unpublished trials that would likely influence this review.
 
Summary of Evidence
The evidence for vagal nerve blocking therapy in individuals who have obesity includes 2 sham-controlled randomized controlled trials (RCTs). Relevant outcomes are change in disease status, morbid events, quality of life and treatment-related morbidity. The primary efficacy outcome, at least a 10% difference between groups, was not met for either trial. In the first trial, the observed difference in EWL between\ groups at 12 months was 1%. In the more recent trial, the observed difference in EWL between groups was 8.5%. In a post hoc analysis, the 8.5% EWL was statistically significant, but this magnitude of change may not be clinically significant according to the investigators’ original trial design decisions. Additional analyses of data from the second trial found a difference in EWL at 18 months of approximately 13%. However, these are post hoc analyses that are considered preliminary and need to be replicated in additional appropriately-designed RCTs. In addition, the 18-month data have potential biases, including missing data, combining data from different follow-up visits and impacts of unblinding. The 2 RCTs found that vagal nerve blocking was reasonably safe in terms of serious adverse events during follow-up, although a substantial number of mild and moderate adverse events were reported. The evidence is insufficient to determine the effects of the technology on health outcome.
 
2017 Update
A literature search conducted through April 2017 did not reveal any new information that would prompt a change in the coverage statement.
 
Twenty-four-month outcomes from the ReCharge trial were published by Apovian et al in 2016 (Apovian, 2016). The investigators noted that the sham arm was no longer a valid comparator at 24 months due to crossovers, dropouts, and patient unblinded at 12 months. There was no prespecified statistical analysis plan for assessments after the 12-month primary outcome assessment, including those in this 2016 article. A total of 103 (43%) patients of 239 randomized patients completed the 24-month follow-up. Their mean EWL was 21% (95% CI, 16% to 26%) and mean total weight loss was 8% (95% CI, 6% to 10%). No serious treatment-related adverse events were reported in the 18- to 24-month time period. The analysis lacked a blinded comparison group, and, like the 18-month data, was post hoc.
 
A position statement published in 2016 by the American Society for Metabolic and Bariatric Surgery includes the following conclusions and recommendations on vagus nerve blocking therapy for treatment of obesity (Papasavas, 2016):
 
“1. Reversible vagal nerve blockade has been shown to result in statistically significant EWL [excess weight loss] at 1 year compared with a control group in one of 2 prospective randomized trials.
2. Reversible vagal nerve blockage has been shown to have a reasonable safety profile with a low incidence of severe adverse events and a low revisional rate in the short term. More studies are needed to determine long-term reoperation and explantation rates.
3. The prospective collection of VBLOC [vagus nerve blocking] outcomes as part of the national center of excellence databases is encouraged to establish the long-term efficacy of this new technology.”
 
The evidence remains insufficient to determine the effects of this technology on health outcomes.
 
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2018. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:
0312TVagus nerve blocking therapy (morbid obesity); laparoscopic implantation of neurostimulator electrode array, anterior and posterior vagal trunks adjacent to esophagogastric junction (EGJ), with implantation of pulse generator, includes programming
0313TVagus nerve blocking therapy (morbid obesity); laparoscopic revision or replacement of vagal trunk neurostimulator electrode array, including connection to existing pulse generator
0314TVagus nerve blocking therapy (morbid obesity); laparoscopic removal of vagal trunk neurostimulator electrode array and pulse generator
0315TVagus nerve blocking therapy (morbid obesity); removal of pulse generator
0316TVagus nerve blocking therapy (morbid obesity); replacement of pulse generator
0317TVagus nerve blocking therapy (morbid obesity); neurostimulator pulse generator electronic analysis, includes reprogramming when performed

References: Apovian CM, Shah SN, Wolfe BM, et al.(2016) Two-year outcomes of vagal nerve blocking (vBloc) for the treatment of obesity in the ReCharge Trial. Obes Surg. Aug 10 2016. PMID 27506803

Flegal KM, Kit BK, Orpana H, et al.(2013) Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. Jan 2 2013;309(1):71-82. PMID 23280227

Ikramuddin S, Blackstone RP, Brancatisano A, et al.(2014) Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the ReCharge randomized clinical trial. JAMA. Sep 3 2014;312(9):915-922. PMID 25182100

Ogden CL, Carroll MD, Kit BK, et al.(2014) Prevalence of childhood and adult obesity in the United States, 2011-2012. Feb 26 2014;311(8):806-814. PMID 24570244

Papasavas P, El Chaar M, Kothari SN, et al.(2016) American Society for Metabolic and Bariatric Surgery position statement on vagal blocking therapy for obesity. Surg Obes Relat Dis. Mar-Apr 2016;12(3):460-461. PMID 26948945

Sarr MG, Billington CJ, Brancatisano R, et al.(2012) The EMPOWER study: randomized, prospective, double-blind, multicenter trial of vagal blockade to induce weight loss in morbid obesity. Obes Surg. Nov 2012;22(11):1771-1782. PMID 22956251

Shikora SA, Wolfe BM, Apovian CM, et al.(2015) Sustained weight loss with vagal nerve blockade but not with sham: 18-month results of the ReCharge trial. J Obes. 2015;2015:365604. PMID 26246907

Summary of Safety and Effectiveness Data (SSED): Maestro Rechargeable System. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cftopic/pma/pma.cfm?num=p130019. Accessed March 17, 2015.

U.S. Preventive Services Task Force. Obesity in Adults: Screening and Management. 2012; http://www.uspreventiveservicestaskforce.org/Page/Topic/recommendation-summary/obesity-in-adults-screening-and-management. Accessed March 3, 2015.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2019 American Medical Association.