Stuart J Spechler1, John G Hunter1, Karen M Jones1, Robert Lee1, Brian R Smith1, Hiroshi Mashimo1, Vivian M Sanchez1, Kerry B Dunbar1, Thai H Pham1, Uma K Murthy1, Taewan Kim1, Christian S Jackson1, Jason M Wallen1, Erik C von Rosenvinge1, Jonathan P Pearl1, Loren Laine1, Anthony W Kim1, Andrew M Kaz1, Roger P Tatum1, Ziad F Gellad1, Sandhya Lagoo-Deenadayalan1, Joel H Rubenstein1, Amir A Ghaferi1, Wai-Kit Lo1, Ronald S Fernando1, Bobby S Chan1, Shirley C Paski1, Dawn Provenzale1, Donald O Castell1, David Lieberman1, Rhonda F Souza1, William D Chey1, Stuart R Warren1, Anne Davis-Karim1, Shelby D Melton1, Robert M Genta1, Tracey Serpi1, Kousick Biswas1, Grant D Huang1. 1. From the Department of Medicine and Center for Esophageal Diseases, Baylor University Medical Center at Dallas, Baylor Scott & White Health, and the Department of Medicine, Veterans Affairs (VA) North Texas Health Care System (S.J.S., R.F.S.), and the Departments of Medicine (K.B.D.), Surgery (T.H.P.), and Pathology (S.D.M.), VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, and the Department of Pathology, Baylor College of Medicine, Houston (R.M.G.); the Departments of Surgery (J.G.H.) and Medicine (D.L.), Oregon Health and Science University, and the Department of Medicine, VA Portland Health Care System (D.L.) - both in Portland; the VA Cooperative Studies Program Coordinating Center, Perry Point (K.M.J., T.S., K.B.), and the Departments of Medicine (E.C.R.) and Surgery (J.P.P.), VA Maryland Health Care System and University of Maryland School of Medicine, Baltimore - all in Maryland; the Departments of Medicine (R.L.) and Surgery (B.R.S.), VA Long Beach Healthcare System and University of California, Irvine, Irvine, the Departments of Medicine (C.S.J., R.S.F., B.S.C.) and Surgery (J.M.W.), VA Loma Linda Healthcare System and Loma Linda University Medical Center, Loma Linda, and the Department of Surgery, University of Southern California, Los Angeles (A.W.K.) - all in California; the Department of Medicine, VA Boston Healthcare System, Harvard Medical School (H.M., W.-K.L.), and the Department of Surgery, VA Boston Healthcare System, Boston University School of Medicine (V.M.S.), Boston; the Departments of Medicine (U.K.M.) and Surgery (T.K.), Syracuse VA Medical Center and SUNY Upstate Medical University, Syracuse, NY; the Department of Medicine, VA Connecticut Healthcare System and Yale University, New Haven, CT (L.L.); the Departments of Medicine (A.M.K., S.C.P.) and Surgery (R.P.T.), VA Puget Sound Health Care System and University of Washington School of Medicine, Seattle; the Departments of Medicine (Z.F.G., D.P.) and Surgery (S.L.-D.), Durham VA Medical Center and Duke University Medical Center, Durham, NC; the Departments of Medicine (J.H.R.) and Surgery (A.A.G.), VA Ann Arbor Healthcare System, and the Departments of Medicine (J.H.R., W.D.C.) and Surgery (A.A.G.), University of Michigan - both in Ann Arbor; the Department of Medicine, Medical University of South Carolina, Charleston (D.O.C.); the VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, NM (S.R.W., A.D.-K.); and the VA Office of Research and Development, Washington, DC (G.D.H.).
Abstract
BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS:Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg ofomeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).
RCT Entities:
BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS:Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERDesophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).
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Authors: Rena Yadlapati; Melina Masihi; C Prakash Gyawali; Dustin A Carlson; Peter J Kahrilas; Billy Darren Nix; Anand Jain; Joseph R Triggs; Michael F Vaezi; Leila Kia; Alexander Kaizer; John E Pandolfino Journal: Gastroenterology Date: 2020-09-16 Impact factor: 22.682