Coverage Policy Manual
Policy #: 2003045
Category: Surgery
Initiated: January 1995
Last Review: May 2018
  Gastric Neurostimulation for Treatment of Gastric and/or Small Bowel Paresis

Description:
Gastric neurostimulation is performed using an implantable device designed to treat chronic drug-refractory nausea and vomiting secondary to gastroparesis of diabetic or idiopathic etiology.  The device may be referred to as a gastric pacemaker.
 
Currently, only 1 gastric electrical stimulator has received approval from the U.S. Food and Drug Administration (FDA) (see note below), the Gastric Electrical Stimulator (GES) System, manufactured by Medtronic. The Enterrra® Gastric Neurostimulator GES system consists of 4 components: the implanted pulse generator, 2 unipolar intramuscular stomach leads, the stimulator programmer, and the memory cartridge. With the exception of the intramuscular leads, all other components have been used in other implantable neurological stimulators, such as spinal cord or sacral nerve stimulation. The intramuscular stomach leads are implanted either laparoscopically or during a laparotomy and are connected to the pulse generator that is implanted in a subcutaneous pocket. The programmer sets the stimulation parameters, which are typically set at an on time of 0.1 sec alternating with an off time of 5.0 sec.
 
Gastroparesis is a chronic disorder of gastric motility characterized by delaying emptying of a solid meal. Symptoms include bloating, distension, nausea, and vomiting. When severe and chronic, gastroparesis can be associated with dehydration, poor nutritional status, and poor glycemic control in diabetics. While most commonly associated with diabetes, gastroparesis is also found in chronic pseudo-obstruction, connective tissue disorders, Parkinson’s disease, and psychological pathologic conditions. Treatment of gastroparesis includes prokinetic agents such as cisapride and metoclopramide, and antiemetic agents such as metoclopramide, granisetron, or ondansetron Severe cases may require enteral or total parenteral nutrition.
 
Note: It should be noted that the Enterrra® Gastric Neurostimulator GES System received FDA approval through a “humanitarian device exemption.” This regulatory category was established in 1996 and only applies to devices intended to benefit less than 4,000 patients. The approval process is similar to that of a premarket approval application (PMA), but is exempt from the effectiveness requirements of a PMA. Thus the application is not required to provide results of scientifically valid clinical investigations, but must contain sufficient information for the FDA to determine that the device does not pose unreasonable or significant risk of illness or injury. A humanitarian use device may only be used in facilities that have an Institutional Review Board (IRB) to supervise clinical testing of the device.
 
Gastric neurostimulation for the treatment of obesity is addressed in policy #2007009.

Policy/
Coverage:
Effective September 2011
For fully-insured groups, as required by Arkansas Code Title 23, Chapter 99, Subchapter 4, 23-99-418, gastric neurostimulators are covered for the treatment of chronic intractable, drug refractory, nausea and vomiting secondary to gastroparesis of diabetic or idiopathic etiology. Gastric Stimulators may be used only in medical centers in which the performing facility's Institutional Review Board has approved use of the device.
 
Note: The Enterra® Therapy (GES) for gastroparesis received Humanitarian Device Exemption approval from the Food and Drug Administration.  However, as stated in Arkansas ACT 1042, 2011, the effectiveness of Enterra® Therapy (gastric electrical stimulation) for the treatment of gastroparesis has not been demonstrated.
 
For those contracts that are not mandated by state law, gastric neurostimulation (including analysis, programming and reprogramming) does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes because available scientific evidence regarding its effectiveness is in conflict and the subject of ongoing debate.
 
For those contracts that are not mandated by state law and do not have primary coverage criteria, gastric neurostimulation (including analysis, programming and reprogramming) is considered investigational. Investigational services are excluded in the member benefit certificate.
 
 
Effective prior to May 2011
Gastric neurostimulation for, but not limited to, the treatment of gastroparesis,  is a contract exclusion in most member benefit contracts and is not covered.
 
Gastric neurostimulation is not covered because available scientific evidence regarding its effectiveness is in conflict and the subject of ongoing debate; it is therefore not covered in accordance with the Primary Coverage Criteria.
 
Gastric neurostimulation is considered investigational and is not covered by contracts without primary coverage criteria language.  Investigational services are excluded in the member benefit certificate.
 
Electronic analysis and programming or reprogramming of a gastric neurostimulator is also not covered since gastric neurostimulation for any reason is not covered.
 
 

Rationale:
The data presented to the FDA documenting the “probable benefit” of the Gastric Electrical Stimulation (GES) system was based on a multicenter double-blind crossover study referred to as the WAVESS study (Worldwide Anti-Vomiting Electrical Stimulation Study).  The study included 33 patients with intractable idiopathic or diabetic gastroparesis. The primary endpoint of the study was a reduction in vomiting frequency, as measured by patient diaries. In the initial phase of the study, all patients underwent implantation of the stimulator and were randomly and blindly assigned to stimulation ON or stimulation OFF for the first month, with crossover to OFF and ON during the second month. The baseline vomiting frequency was 47 episodes per month, which significantly declined in both ON and OFF groups to 23 to 29 episodes, respectively. However, no significant differences were found in the number of vomiting episodes between the 2 groups, suggesting a placebo effect.
 
2007 Update
A literature review was conducted  through  April 2007. Results of that review did not identify clinical studies that would alter either of the policy statements.
 
Investigators continue to publish case series with 2- to 3-year follow-up of patients who received GES for refractory gastroparesis. However, none of the published studies are randomized controlled trials. Lin and colleagues reported on outcomes beyond 3 years in patients receiving GES for gastroparesis.  Of 55 patients, 10 died of non-pacemaker-related complications, 6 had the devices removed and 2 could not be reached. In the remaining 37 patients, symptoms, hospital days, and the use of medications had sustained reductions (from baseline) beyond 3 years. Mason and colleagues reported on the 20-month follow-up of 27 of 29 patients referred for gastrectomy who instead received GES for refractory gastroparesis.  Three patients required additional procedures due to poor outcomes. Nutritional support was discontinued in the 19 patients who were dependent on supplemental feeding prior to the procedure. Gastric emptying rates improved. While these results are encouraging, given the findings of the WAVESS study, randomized trials are needed to determine the efficacy of GES in gastroparesis.
 
The American Motility Society Task Force on Gastroparesis stated , while results of  investigations are encouraging, “the clinical benefits of gastric electric stimulation have not been unequivocally demonstrated or the site of action.  A larger, longer duration, sham-stimulation controlled, multicentre trial of gastric electrical stimulation is ongoing in patients with gastroparesis.  Optimal pulse parameters need to be defined and predictors of clinical improvement must be characterized.”
 
2008 update
The policy was updated with a literature review using MEDLINE in January 2008. None of the publications reported results on a randomized controlled trial of GES for gastroparesis. Anand and colleagues reported on 214 consecutive drug-refractory patients with the symptoms of gastroparesis (146 idiopathic, 45 diabetic, 23 after surgery) who consented to participate in a variety of clinical research and clinical protocols at 3 centers from January 1992 through January 2005, resulting in 156 patients implanted with a gastric electrical stimulation device and 58 patients as controls.  At last follow-up, median 4 years, most patients implanted (135 of 156) were alive with intact devices, significantly reduced gastrointestinal symptoms, and improved health-related quality of life, with evidence of improved gastric emptying, and 90% of the patients had a response in at least 1 of 3 main symptoms. Most patients explanted, usually for pocket infections, were later reimplanted successfully. Based on a series of 15 patients, Gourcerol reported that high-frequency gastric electrical stimulation could be an effective therapy for treating intractable nausea and vomiting whether or not gastric emptying was delayed.  In an editorial accompanying the Anand study, Ang comments that without an appropriate control group, the contribution of a placebo effect to the treatment group cannot be excluded.  This editorial comments on the scarce literature about long-term outcome of severe gastroparesis, but that follow-up case series of those who require tube feeding suggest an overall improvement over time. The editorial also notes that given the high costs involved, the unknown mechanism of action, and the absence of rigorous well-controlled randomized trials, that “we should exercise caution” before embracing GES as a standard of care.
 
2010 Update
A search of the MEDLINE database through October 2010 identified no randomized controlled trials that evaluated the use of gastric electrical stimulation (GES) compared to other treatments for any indication.
 
Small case series with short follow-up are reported. Brody and colleagues report on the largest of the series, with 50 patients (20 diabetic, 25 idiopathic, 2 postsurgical, and 3 connective tissue disorders). Thirty-five patients (70%) were available for follow-up at 6 months and 30 were available at 12 months. Total symptom severity score (19.05 + 8.05) decreased at 6 (12.92 + 7.41, p<0.001) and 12 months (14.05 + 8.28, p<0.01). Total frequency score (20.39 + 8.08) decreased at 6 months (15.01 + 7.37, p<0.01) and 12 months (15.71 + 7.40, p<0.05). Gastric retention at 2 hours decreased from 66% to 50% (p<0.04) and normalized in 11 of 27 patients (Brody, 2008).  
 
In a recent publication, McCallum and colleagues performed a multicenter prospective study to evaluate GES (Enterra therapy) in patients with chronic intractable nausea and vomiting from diabetic gastroparesis (DGP) (McCallum, 2010).  In this study, 55 patients with refractory DGP (5.9 years of DGP) were given implants of the Enterra system. After surgery, all patients had the stimulator turned on for 6 weeks and then they randomly were assigned to groups that had consecutive 3-month cross-over periods with the device on or off. After this period, the device was turned on in all patients and they were followed up unblinded for 4.5 months. During the initial 6-week phase with the stimulator turned on, the median reduction in weekly vomiting frequency (WVF) compared with baseline was 57%. There was no difference in WVF between patients who had the device turned on or off during the 3-month cross-over period. At one year, the WVF of all patients was significantly lower than baseline values (median reduction, 68%; P<0.001). One of the patients had the device removed due to infection; two patients required surgical intervention due to lead-related problems.
 
In the absence of large, high-quality randomized controlled trials, the policy statement is unchanged. The impact of this technology on health outcomes is not known.
 
2011 Update
The policy was updated with a search of the MEDLINE database. No randomized trials were identified that  evaluated use of gastric electrical stimulation (GES) compared to other treatments for gastroparesis. The policy statement is unchanged.
 
2014 Update
A search of the MEDLINE database through January 2014 did not reveal any new randomized controlled trials that would prompt a change in the coverage statement. The following is a summary of the key identified literature.
 
Several trials were identified that evaluated the use of a temporary gastric stimulator. Temporary stimulators are intended to be used to determine whether or not an individual patient will respond to GES prior to undertaking a permanent implant. In 2013, Lahr and colleagues reported significant improvement during temporary GES (placement for at least 4 days) in 95 drug-refractory patients with symptoms of gastroparesis (abdominal pain, bloating, early satiety, nausea, vomiting) (Lahr, 2013).  For the entire group of patients, abdominal pain decreased from a baseline of 2.95 on a 0-4 modified Likert scale to 1.12 after temporary GES (p<0.001). In a sub-set of patients reporting severe pain at baseline (n=68), as defined by a score of 3-4 on the pain scale, mean pain scores decreased from 3.62 to 1.29 (p<0.001). There were also reductions of similar magnitude on symptom scores for early satiety, abdominal distension, nausea, and vomiting (Lahr, 2013).
 
Abell et al. (Abell, 2011) performed a trial of temporary GES in 58 patients with 1 of 3 etiologies (idiopathic, diabetic, postsurgical). A temporary device was placed in all patients with the device turned on or off for 4 consecutive days, followed by cross-over to the other group for an additional 4-day period. The frequency of vomiting decreased in both groups. At day 3, the decrease in vomiting was significantly greater for the GES group; however, by day 8, the differences between groups were no longer significant.
 
Andersson et al. (Andersson, 2011) tested a temporary GES in 27 patients with drug-refractory nausea/vomiting. Fourteen patients were treated with temporary GES in open-label fashion, and 13 had a randomized, cross-over trial in which the device was turned on for 12-14 days and off for 12-14 days. These authors reported that the majority of patients (22/27) improved following GES placement. Of the 13 patients in the randomized cross-over phase, 6 had improvement in symptoms during the on period and 7 did not. Of the 7 patients who did not improve during the on period, there was improvement with an increased intensity of stimulation.
 
GES placement using minimally invasive surgical approaches has also been evaluated in several publications. Laparoscopy has been reported in at least two studies as a feasible approach in placement of GES for patients with medically refractory diabetic or idiopathic gastroparesis (Timratana, 2013; Zehetner, 2013).
 
The American College of Gastroenterology published a clinical practice guideline on management of gastroparesis in 2013 (Camilleri, 2013). The recommendations for this guideline were based on review of the evidence base through 2011. The evidence on GES consisted of the two randomized crossover trials and the case series, as described above. The recommendation for GES was that “GES may be considered for compassionate treatment in patients with refractory symptoms, particularly nausea and vomiting. Symptom severity and gastric emptying have been shown to improve in patients with DG [diabetic gastroparesis], but not in patients with IG [idiopathic gastroparesis] or PSG [postsurgical gastroparesis]. [Conditional recommendation (there is uncertainty about trade-offs), moderate level of evidence (further research would be likely to have an impact on the confidence in the estimate of effect)]” (Camilleri, 2013).
 
In summary, the evidence on the efficacy of gastric electrical stimulation to treat gastroparesis is inadequate to permit scientific conclusions. Only two small randomized studies have been published on the treatment of gastroparesis. In one randomized study (Abell, 2003), only 33 patients recruited from 11 centers in the United States were included. There was no statistically significant improvement in symptoms for the entire study group compared to placebo, but positive results were reported for the subgroup of 17 patients with diabetic gastroparesis. In the other randomized study of 55 patients (McCallum, 2010), while weekly vomiting frequency was significantly lower than baseline values at one-year follow-up, there was no difference in weekly vomiting frequency between patients who had the device turned on or off during the 3-month cross-over period. The case series report improvements in symptoms, nutritional parameters, and quality of life. However, the lack of a control group precludes the conclusion that these changes are due to treatment with gastric electrical stimulation, given the variable natural history of gastroparesis, and the expected placebo effect.
 
2016 Update
A literature search conducted through April 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
A 2015 systematic review by Lal and colleagues identified 21 studies with at least 10 participants who were treated with GES for gastroparesis and followed for at least 6 months (Lal, 2015).Most of the studies were observational. Outcome measures varied and the authors did not pool study findings. The authors reported that most studies reported a reduction in symptom severity, but changes in gastric emptying were variable and generally were not correlated with symptom improvement.
 
In 2015, Brody and colleagues reported on 79 patients who were refractory to nonoperative gastroparesis treatments who underwent GES implantation (Brody, 2015). After 1 year, 16 of 52 patients with available data (30.8%) had at least a 25% reduction in pain, and 23 of 52 (44.2%) had at least a 25% reduction in functional symptom severity, compared with baseline. Eighteen patients had 4- to 8-year follow-up data. Compared with baseline, 6 of 18 (33.3%) reported at least a 25% in pain, and 12 (66.7%) reported at least a 25% in functional symptom severity. There was no 30-day mortality, but 11 patients (14%) died over the 10-year study period. None of the deaths were GES-related.
 
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed below:
Ongoing
(NCT00903799) Clinical Efficacy and Efficiency of Gastric Electrical Stimulation (Enterra®) for Refractory Nausea and/or Vomiting; planned enrollment 220; completion date February 2016.
 
((NCT01823705) Gastric Electrical Stimulation (GES) for the Treatment of Obesity; planned enrollment 30; completion date September 2016.
 
(NCT00568373) Gastric Electric Stimulation-Enterra Therapy for the Treatment of Chronic Intractable (Drug Refractory) Nausea and Vomiting Secondary to Gastroparesis of Diabetic or Idiopathic Etiology; planned enrollment 200; completion date December 2016.
 
(NCT02164591) Escalating Temporary Gastric Electrical Stimulation for Severe Gastroparesis; planned enrollment 200; completion date December 2017.
 
2017 Update
A literature search conducted through April 2017 did not reveal any new information that would prompt a change in the coverage statement.
 
One systematic review and meta-analysis published by Levinthal et al was identified. (Levinthal, 2017). To be included in the Levinthal review, studies had to include adults with established gastroparesis, report patient symptom scores and administer treatment for at least 1 week. Five randomized controlled trials (RCTs) and 13 non-RCTs meeting criteria were identified. Pooled analysis of data from the 5 RCTs (n=185 patients) did not find a statistically significant difference in symptom severity when the GES was turned on versus off (standardized mean difference [SMD], 0.17; 95% confidence interval [CI], -0.06 to 0.40; p=0.15). Another pooled analysis did not find a statistically significant difference in nausea severity scores when the GES was on or off (SMD = -0.143; 95% CI, -0.50 to 0.22; p=0.45). In a pooled analysis of 13 open-label single-arm studies and data from open-label extensions of 3 RCTs, mean total symptom severity score decreased 2.68 (95% CI, 2.04 to 3.32) at follow-up from a mean of 6.85 (95% CI, 6.28 to 7.42) at baseline. The rate of adverse events in the immediate postoperative period (reported in 7 studies) was 8.7% (95% CI, 4.3% to 17.1%). The in-hospital mortality rate within 30 days of surgery was 1.4% (95% CI, 0.8% to 2.5%), the rate of reoperations (up to 10 years of follow-up) was 11.1% (95% CI, 8.7% to 14.1%), and the rate of device removal was 8.4% (95% CI, 5.7% to 12.2%).
 
The 2017 meta-analysis of these 5 RCTs did not find a significant benefit of GES on the severity of symptoms associated with gastroparesis (Levinthal, 2017). Patients generally reported improved symptoms at follow-up whether or not the device was turned on, suggesting a placebo effect. The evidence is insufficient to determine the effects of the 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:
43647Laparoscopy, surgical; implantation or replacement of gastric neurostimulator electrodes, antrum
43648Laparoscopy, surgical; revision or removal of gastric neurostimulator electrodes, antrum
43659Unlisted laparoscopy procedure, stomach
43881Implantation or replacement of gastric neurostimulator electrodes, antrum, open
43882Revision or removal of gastric neurostimulator electrodes, antrum, open
43999Unlisted procedure, stomach
64590Insertion or replacement of peripheral or gastric neurostimulator pulse generator or receiver, direct or inductive coupling
64595Revision or removal of peripheral or gastric neurostimulator pulse generator or receiver
95980Electronic analysis of implanted neurostimulator pulse generator system (eg, rate, pulse amplitude and duration, configuration of wave form, battery status, electrode selectability, output modulation, cycling, impedance and patient measurements) gastric neurostimulator pulse generator/transmitter; intraoperative, with programming
95981Electronic analysis of implanted neurostimulator pulse generator system (eg, rate, pulse amplitude and duration, configuration of wave form, battery status, electrode selectability, output modulation, cycling, impedance and patient measurements) gastric neurostimulator pulse generator/transmitter; subsequent, without reprogramming
95982Electronic analysis of implanted neurostimulator pulse generator system (eg, rate, pulse amplitude and duration, configuration of wave form, battery status, electrode selectability, output modulation, cycling, impedance and patient measurements) gastric neurostimulator pulse generator/transmitter; subsequent, with reprogramming

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Abell TL, Johnson WD, Kedar A et al.(2011) A double-masked, randomized, placebo-controlled trial of temporary endoscopic mucosal gastric electrical stimulation for gastroparesis. Gastrointest Endosc 2011; 74(3):496-503 e3.

American Motility Society Task Force on Gastroparesis.(2006) Treatment of gastroparesis: a multidisciplinary clinical review. Neurogastroenterol Motil, 2006; 18:263-83.

Anand C, Al-Juburi A, et al.(2007) Gastric electrical stimulation is safe and effective: a long-term study in patients with drug refractory gastroparesis in three regional centers. Digestion, 2007; 75:83-9.

Andersson S, Ringstrom G, Elfvin A et al.(2011) Temporary percutaneous gastric electrical stimulation: a novel technique tested in patients with non-established indications for gastric electrical stimulation. Digestion 2011; 83(1-2):3-12.

Ang D, Tack J.(2007) Gastric electrical stimulation for the treatment of gastroparesis: ready for prime time? Digestion, 2007; 75:80-2.

Brody F, Vaziri K, Saddler A et al.(2008) Gastric electrical stimulation for gastroparesis. J Am Coll Surg 2008; 207(4):533-8.

Brody F, Zettervall SL, Richards NG, et al.(2015) Follow-up after gastric electrical stimulation for gastroparesis. J Am Coll Surg. Jan 2015;220(1):57-63. PMID 25458798

Camilleri M, Parkman HP, Shafi MA et al.(2013) Clinical guideline: management of gastroparesis. Am J Gastroenterol 2013; 108(1):18-37; quiz 38.

Camilleri M.(2007) Diabetic gastroparesis. NEJM, 2007; 356:820-9.

Forster J, Sarosiek I, Delcore R, et al.(2001) Gastric pacing is a new surgical treatment for gastroparesis. Am J Surg 2001; 182(6):676-81.

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Heckert J., Sankineni A., Hughes WB., et al.(2015) Gastric electric stimulation for refractory gastroparesis: a prospective analysis of 151 patients at a single center. Dig Dis Sci. 2015 Aug 18 [epub ahead of print].

Islam S., McLaughlin J., Pierson J., et al.(2015) Log-term outcomes of gastric electical stimulation in children with gastroparesis. J Pediatr Surg. 2015 Oct 23. [epub ahead of print].

Lahr CJ, Griffith J, Subramony C et al.(2013) Gastric electrical stimulation for abdominal pain in patients with symptoms of gastroparesis. Am Surg 2013; 79(5):457-64.

Lal N, Livemore S, Dunne D, et al.(2015) Gastric Electrical Stimulation with the Enterra System: A Systematic Review. Gastroenterol Res Pract. 2015;2015:762972. PMID 26246804

Levinthal DJ, Bielefeldt K.(2017) Systematic review and meta-analysis: Gastric electrical stimulation for gastroparesis. Auton Neurosci. Jan 2017;202:45-55. PMID 27085627

Lin Z, Forster J, Sarosiek I, et al.(2004) Treatment of diabetic gastroparesis by high-frequency gastric electrical stimulation. Diabetes Care 2004; 27(5):1071-6.

Lin Z, Sarosiek I, et al.(2006) Symptom responses, long-term outcomes and adverse events beyond 3 years of high-frequency gastric electrical stimulation for gastroparesis. Neurogastroenterol Motil, 2006; 18:18-27.

Mason RJ, Lipham J, et al.(2005) Gastric electrical stimulation. Arch Surg, 2005; 140:841-8.

McCallum R, Lin Z, Wetzel P, et al.(2005) Clinical response to gastric electrical stimulation in patients with postsurgical gastroparesis. Clin Gastroenterol Hepatol 2005; 3(1):49-54.

McCallum RW, Snape W, Brody F et al.(2010) Gastric electrical stimulation with Entera therapy improves symptoms from diabetic gastroparesis in a prospective study. Clin Gastroenterol Hepatol 2010 [epub ahead of print].

McCallum RW, Snape W,(2010) Gastric electrical stimulation with Enterra therapy improves symptoms from diabetic gastroparesis in a prospective study. Clin Gastroenterol Hepatol 2010 [Epub ahead of print].

Parkman HP, Hasler WL, Fisher RS.(2004) American Gastroenterological Association Technical Review on the diagnosis and treatment of gastroparesis. Gastroenterology 2004; 127:1592-1622.

Timratana P, El-Hayek K, Shimizu H et al.(2013) Laparoscopic gastric electrical stimulation for medically refractory diabetic and idiopathic gastroparesis. J Gastrointest Surg 2013; 17(3):461-70.

www.fda.gov/cdrh/ode/H990014sum.html; 2001.

Zehetner J, Ravari F, Ayazi S et al.(2013) Minimally invasive surgical approach for the treatment of gastroparesis. Surg Endosc 2013; 27(1):61-6.


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.
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