PHILADELPHIA – The first trial conducted in gastroesophageal reflux diseases that employed control of regurgitation as a primary endpoint found a significant advantage for transoral fundoplication over a sham procedure, according to the results presented at the American College of Gastroenterology (ACG).
On the basis of these results “TF [transoral fundoplication] should be considered in GERD [gastroesophageal reflux disease] patients with small or absent hiatal hernia who suffer from troublesome regurgitation despite PPI therapy,” reported Dr. Peter J. Kahrilas, the Gilbert H. Marquardt Professor of Medicine, a professor of medicine, gastroenterology, and hepatology, at Northwestern University, Chicago*.
Dr. Peter J. Kahrilas
The focus on regurgitation in this trial was partially driven by the lack of previous evidence for an effective therapy. In those trials that have included change in regurgitation among secondary endpoints, Dr. Kahrilas said control on this symptom has typically been “significantly less” than that observed with heartburn.
In this study, called RESPECT, 129 patients were randomized in a 2:1 ratio to TF performed with the Esophyx device or to a sham procedure. Both groups were initiated on a standard dose of proton pump inhibitors (PPIs), but PPIs were discontinued in the TF arm 2 weeks after the procedure. In the sham group, an increase in PPI dose was permitted at the 2-week and 12-week assessments in those not already at the maximum double the standard dose limit.
The primary endpoint was elimination of troublesome regurgitation based on the regurgitation-related fields from the Reflux Disease Questionnaire (RDQ), which is a validated tool for GERD assessment. On this basis, symptoms at the final 26-week assessment had resolved in 67% of patients randomized to TF and 25% (P = .023) randomized to the sham procedure. Early failure rates were also significantly lower in the TF group (11% vs. 36%; P = .002).
Intraesophageal acid levels assessed with 48-hour pH monitoring at the end of the study “were improved but not normalized in the TF group and unchanged in the sham group,” Dr. Kahrilas reported.
Adverse events, although more common in the TF group, were infrequent in both arms, and none were serious. Summarizing risk of adverse events, Dr. Kahrilas said, “TF appears safe without typical fundoplication side effects.”
The specific mechanism of benefit for controlling regurgitation has not been defined, but Dr. Kahrilas suggested, “We think we are restricting the volume of reflux.”
Regurgitation is “the ignored symptom of GERD,” according to Dr. Kahrilas. Although this symptom can be significant to patients, clinicians have had limited treatment options.
This point was emphasized by Dr. Nicholas Shaheen, director, Center for Esophageal Diseases and Swallowing, University of North Carolina, Chapel Hill. In an interview, Dr. Shaheen said effective therapy for regurgitation is an unmet need.
“Patients with predominant regurgitation are not uncommon and PPIs do appear to be less effective for this symptom,” Dr. Shaheen reported. “Having a treatment option with efficacy specific for this symptom could be helpful.”
Dr. Peter Kahrilas has numerous financial relationships with pharmaceutical companies including EndoGastric, the sponsor of this trial.
*Correction, 10/27/2014: An earlier version of this article misstated Dr. Kahrilas' position.