Transoral Fundoplication Provides Better GERD Symptom Control Than PPIs in Patients With Troublesome Regurgitation: A Multicenter Sham-Controlled Randomized Clinical Trial

Introduction: Transoral esophagogastric fundoplication (TF) can decrease or eliminate gastroesophageal reflux disease (GERD) symptoms in selected patients with persistent symptoms on proton pump inhibitors (PPIs). We aimed to determine if TF provided better control of troublesome regurgitation than PPIs in patients with well-documented GERD. Methods: The Randomized Esophyx vs Sham, PlacEbo-Controlled Transoral fundoplication (RESPECT) trial was carried out at eight academic and community medical centers across the United States and was approved by the Institutional Review Board of each site. Six hundred ninety-six patients with troublesome regurgitation, despite daily PPI of at least 40 mg/day, were screened with 3 validated GERD-specific symptom scales. Scores were obtained on and off PPIs. Those with at least ‘troublesome’ regurgitation (Montreal definition) on PPIs underwent barium swallow, esophagogastroduodenoscopy (EGD), 48-hr esophageal pH monitoring, and high-resolution esophageal manometry. One hundred twenty-nine patients with well-proven GERD and hiatal hernia (HH) ≤2 cm were randomized 2:1 to either TF and six months of placebo, or sham surgery and 6 months of daily or twice daily PPI (40 mg omeprazole). Patients were blinded to therapy during follow-up and were reassessed at 2, 12, and 26 weeks. At final analysis (6 months), patients were reassessed symptomatically and underwent testing with 48-hr esophageal pH monitoring and EGD. The primary study endpoint was the elimination of troublesome regurgitation, using the regurgitation fields of the RDQ at 6 month follow-up. Results: Six months following operation, 54 of 80 (68%) of patients in the TF/placebo arm reported the elimination of troublesome regurgitation, compared to 17 of 37 patients (46%) of patients in the sham/PPI arm (p=0.041). TF was associated with significant decrease in intraesophageal acid exposure in all parameters measured (p<.001). In sham patients, no improvement in pH control was detected. With the exception of postoperative epigastric pain, complications and adverse effects were no different between TF and sham groups. Early treatment failure was more common in those randomized to sham surgery and PPI than in those randomized to TF and placebo. Dysphagia and bloating were improved in both groups. Conclusion: TF plus bid placebo was more effective than a sham procedure plus PPI (qd or bid) in eliminating troublesome regurgitation for GERD patients enrolled with persistent troublesome regurgitation despite PPI therapy. We believe TF has a role in treating GERD patients with small or absent hiatal hernia who suffer from troublesome regurgitation, despite PPI therapy. Disclosure: Dr Kahrilas has served as a consultant for Reckitt Benckiser, AstraZeneca, and Pfizer. Dr. Hungness received an honorarium as part of faculty for a surgical training course for Baxter. Dr. Hunter is a consultant for EndoGastric Solutions. Dr. Bell is a consultant for EndoGastric Solutions. Dr. Trad is a consultant for and has received a research grant from EndoGastric Solutions. Dr. Wilson received a research grant from EndoGastric Solutions, Apollo Endosurgery, Reshape Medical; and is a consultant for Apollo Endosurgery, Gore Medical and Ethicon. Dr Oelschlager is a consultant for EndoGastric Solutions and has received research support from EndoGastric Solutions. Dr. Reavis is a consultant for EndoGastric Solutions. Drs. Melvin, Burch, Snyder, Perry, Soper and Turgeon do not have any relevant financial relationships to disclose. This research was supported by an industry grant from EndoGastric Solutions (EGS).