Antireflux Surgery Without Preoperative Esophageal Manometry

Overview

The goal of this clinical trial is to learn if people can safely skip a test called esophageal manometry before surgery for acid reflux (gastroesophageal reflux disease, or GERD) or a hiatal hernia. Manometry measures the muscles of the food pipe using a thin tube passed through the nose. The test can be uncomfortable and can delay surgery. The main questions this study aims to answer are whether people can skip manometry and still have good swallowing one year after surgery, and whether skipping the test lowers discomfort, shortens the wait for surgery, and lowers cost. To answer this, researchers will compare two groups. One group will have surgery without manometry. The other group will have manometry first, the way it is usually done. Everyone will get the same operation, a partial wrap called a Toupet fundoplication, so the study tests the value of the test and not the surgery. Participants will be placed by chance into one of the two groups, have the same standard operation, and fill out short questionnaires about their swallowing before surgery and again at 3, 6, and 12 months after surgery. Researchers want to find out if skipping manometry works just as well as the usual approach for people who do not have trouble swallowing before surgery.

BACKGROUND AND RATIONALE Gastroesophageal reflux disease (GERD) and hiatal hernia are among the most common indications for foregut surgery. Laparoscopic antireflux surgery is a durable option for patients who fail or cannot tolerate proton pump inhibitor therapy. The Toupet 270-degree posterior partial fundoplication has become the preferred wrap at high-volume centers because it provides reflux control comparable to the complete Nissen wrap while producing significantly less postoperative dysphagia, as demonstrated across randomized trials and network meta-analysis. High-resolution esophageal manometry (HRM) has traditionally been performed as part of the routine preoperative workup before antireflux surgery. Its historical rationale was threefold: to exclude major motility disorders such as achalasia, to characterize lower esophageal sphincter function, and to detect ineffective esophageal motility in order to guide wrap selection toward a partial fundoplication. The 2023 multi-society consensus guideline on the treatment of GERD now recommends a partial fundoplication for patients with either normal or abnormal manometry findings, which establishes the partial wrap as standard of care regardless of the manometry result. When the operation is already standardized to a Toupet wrap, the principal justification for routine manometry, namely wrap selection, is removed. Manometry is not without burden. It requires transnasal catheter placement and esophageal intubation, is frequently reported as uncomfortable, adds scheduling delays of several weeks in publicly funded systems, and carries a direct cost of approximately 500 to 1,500 US dollars per patient. In patients without overt dysphagia, the prevalence of clinically unsuspected major motility disorders is consistently estimated at less than 2 to 5 percent. Despite this, whether manometry can be safely omitted in this carefully selected population has never been evaluated in a prospective randomized trial. This trial addresses that evidence gap. OBJECTIVES AND HYPOTHESIS The primary objective is to determine whether upfront laparoscopic Toupet 270-degree fundoplication without preoperative manometry is non-inferior to standard manometry-guided care with respect to patient-reported dysphagia at 12 months. The investigators hypothesize that omitting manometry is non-inferior to standard care, because the operation is identical in both arms and patients most likely to harbor an unsuspected motility disorder are excluded at screening. Secondary objectives are to compare reflux-related quality of life, proton pump inhibitor use, 30- and 90-day complications, patient-reported procedural discomfort and anxiety, time from referral to surgery, and direct cost, and to quantify how often manometry findings would have altered operative management. STUDY DESIGN AND SETTING This is a prospective, multicenter, open-label, randomized controlled non-inferiority trial conducted at St. Joseph's Healthcare Hamilton (McMaster University) and Cleveland Clinic. Both sites are high-volume foregut centers with dedicated esophageal motility laboratories, which supports recruitment and the safe management of any participant who requires manometry during the trial. RANDOMIZATION AND ALLOCATION CONCEALMENT Participants are randomized 1:1 through a central, web-based system with concealed allocation, using variable permuted blocks. Randomization is stratified by site, hernia type, and pH testing status. Because ambulatory pH testing is performed at the discretion of the treating surgeon and may influence outcomes independently, pH testing status is used as a stratification variable so that participants who undergo pH testing are balanced between arms, and those who do not are likewise balanced. This preserves internal validity and supports a prespecified subgroup analysis. BLINDING Patients and surgeons cannot be blinded to allocation given the nature of the intervention. Outcome assessors and data analysts are blinded to allocation. STUDY ARMS AND INTERVENTION Participants in the no-manometry arm undergo endoscopy and imaging (computed tomography or upper gastrointestinal study) without preoperative manometry, and proceed directly to surgery. Participants in the standard-workup arm undergo the same endoscopy and imaging plus high-resolution esophageal manometry within eight weeks before surgery. Ambulatory pH testing may be performed at the surgeon's discretion in either arm per institutional practice. In both arms the operation is identical. All participants undergo a standardized laparoscopic Toupet 270-degree posterior partial fundoplication with hiatal hernia repair. The operative standard is defined by a technique manual and includes a five-port laparoscopic approach, complete circumferential gastroesophageal junction dissection, posterior cruroplasty with interrupted non-absorbable sutures, at least 2.5 centimeters of tension-free intra-abdominal esophageal length, and wrap construction sutured to the esophageal wall bilaterally. Intraoperative endoscopy is mandatory in all cases to confirm wrap calibration and adequacy. The operative approach does not vary with manometry findings; this standardization is the key design feature that removes the conventional justification for routine manometry. CROSSOVER AND SAFETY Crossover from the no-manometry arm to manometry is permitted only for intraoperative findings highly suggestive of a primary motility disorder, such as failure of lower esophageal sphincter relaxation or a bird-beak appearance. In such cases the operation is aborted and manometry is arranged postoperatively. Both participating sites have dedicated motility laboratories capable of high-resolution manometry and ambulatory pH testing to manage any such participant. All crossovers are analyzed in the intention-to-treat population and documented as protocol deviations for the per-protocol analysis. This is a minimal-risk trial in which both arms receive standard-of-care surgery; safety is monitored by the investigators through systematic capture of surgical complications graded by the Clavien-Dindo classification. SCHEDULE OF ASSESSMENTS Assessments are collected at screening, baseline, the preoperative visit, surgery, and at 3, 6, and 12 months after surgery. Patient-reported outcomes are administered at baseline and at each postoperative timepoint and are captured electronically in a secure, access-controlled REDCap database hosted through McMaster University, with paper backup. Surgical complications are recorded at 30 and 90 days. SAMPLE SIZE The sample size is based on the primary outcome. Assuming an expected mean dysphagia score of 0.35 with a standard deviation of 0.80, a non-inferiority margin of 0.5 points, a two-sided alpha of 0.05, and 80 percent power, approximately 40 participants per arm are required. Allowing for a conservative 15 percent dropout, the enrollment target is 48 participants per arm, for a total of 96 participants. STATISTICAL ANALYSIS Non-inferiority will be concluded if the upper bound of the two-sided 95 percent confidence interval for the between-arm difference in the primary outcome lies below the prespecified margin of 0.5 points, using a two-sample t-test or a Wilcoxon rank-sum test if the normality assumption is not met. The primary analysis is by intention to treat, with a per-protocol analysis performed as a sensitivity analysis. Secondary outcomes will be analyzed using mixed-effects models for repeated measures, Kaplan-Meier estimation with log-rank testing for time-to-event outcomes, and Fisher exact tests for proportions. Missing data will be handled using multiple imputation under a missing-at-random assumption. A prespecified subgroup analysis by pH testing status will be performed for the primary outcome. DATA MANAGEMENT AND MONITORING Study data are recorded under a unique study identifier, with the linking key stored separately and securely and accessible only to the local study team. The trial is minimal risk and does not use a formal data safety monitoring board; the investigators review enrollment, protocol deviations, and adverse events during accrual, and report serious adverse events and unanticipated problems to the research ethics board within required timelines. ETHICS AND REGISTRATION The trial holds ethics approval from the Hamilton Integrated Research Ethics Board and will be conducted in accordance with the Tri-Council Policy Statement, Good Clinical Practice, and applicable institutional and regulatory requirements at each site. The trial is registered on ClinicalTrials.gov before enrollment of the first participant. SIGNIFICANCE This trial provides the first randomized evidence on whether preoperative manometry can be safely omitted before standardized partial fundoplication in patients without overt dysphagia. A finding of non-inferiority would support simplifying the preoperative pathway, shortening time to surgery, improving patient experience, and reducing cost, and could inform practice guidelines internationally. A neutral result would clarify the true clinical utility of manometry and support more selective rather than routine testing.