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Controlled Clinical Trial
. 2021 Jan;160(1):174-182.e1.
doi: 10.1053/j.gastro.2020.09.013. Epub 2020 Sep 16.

Ambulatory Reflux Monitoring Guides Proton Pump Inhibitor Discontinuation in Patients With Gastroesophageal Reflux Symptoms: A Clinical Trial

Rena Yadlapati  1 , Melina Masihi  2 , C Prakash Gyawali  3 , Dustin A Carlson  2 , Peter J Kahrilas  2 , Billy Darren Nix  3 , Anand Jain  4 , Joseph R Triggs  5 , Michael F Vaezi  6 , Leila Kia  2 , Alexander Kaizer  7 , John E Pandolfino  8
Affiliations
Controlled Clinical Trial

Ambulatory Reflux Monitoring Guides Proton Pump Inhibitor Discontinuation in Patients With Gastroesophageal Reflux Symptoms: A Clinical Trial

Rena Yadlapati et al. Gastroenterology. 2021 Jan.

Abstract

Background and aims: Proton pump inhibitor (PPI) therapy fails to provide adequate symptom control in up to 50% of patients with gastroesophageal reflux symptoms. Although a proportion do not require ongoing PPI therapy, a diagnostic approach to identify candidates appropriate for PPI cessation is not available. This study aimed to examine the clinical utility of prolonged wireless reflux monitoring to predict the ability to discontinue PPIs.

Methods: This double-blinded clinical trial performed over 3 years at 2 centers enrolled adults with troublesome esophageal symptoms of heartburn, regurgitation, and/or chest pain and inadequate PPI response. Participants underwent prolonged wireless reflux monitoring (off PPIs for ≥7 days) and a 3-week PPI cessation intervention. Primary outcome was tolerance of PPI cessation (discontinued or resumed PPIs). Symptom burden was quantified using the Reflux Symptom Questionnaire electronic Diary (RESQ-eD).

Results: Of 128 enrolled, 100 participants met inclusion criteria (mean age, 48.6 years; 41 men). Thirty-four participants (34%) discontinued PPIs. The strongest predictor of PPI discontinuation was number of days with acid exposure time (AET) > 4.0% (odds ratio, 1.82; P < .001). Participants with 0 days of AET > 4.0% had a 10 times increased odds of discontinuing PPI than participants with 4 days of AET > 4.0%. Reduction in symptom burden was greater among the discontinued versus resumed PPI group (RESQ-eD, -43.7% vs -5.3%; P = .04).

Conclusions: Among patients with typical reflux symptoms, inadequate PPI response, and absence of severe esophagitis, acid exposure on reflux monitoring predicted the ability to discontinue PPIs without symptom escalation. Upfront reflux monitoring off acid suppression can limit unnecessary PPI use and guide personalized management. (ClinicalTrials.gov, Number: NCT03202537).

Keywords: Bravo; Functional Heartburn; Gastroesophageal Reflux Disease (GERD); Wireless pH Monitoring.

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Conflict of interest statement

Conflicts of Interest:

RY: Consultant: Medtronic, Ironwood Pharmaceuticals, Diversatek; Research support: Ironwood Pharmaceuticals; Advisory Board: Phatom Pharmaceuticals

CPG: Consultant: Medtronic, Diversatek, Ironwood, Iso-Thrive, Quintiles

DAC: Consultant: Medtronic

PJK: Research support: Ironwood Pharmaceuticals; Advisory Board: Ironwood Pharmaceuticals

MFV: Consultant: Ironwood Pharmaceuticals, Diversatek, Phathom Pharmaceuticals, Daewood

Patent on mucosal integrity by Vanderbilt

JEP: Consultant: Medtronic, Ironwood Pharmaceuticals, Diversatek; Research support: Ironwood Pharmaceuticals, Takeda; Advisory Board: Medtronic, Diversatek; Stock Options: Crospon Inc

MM, BDN, JT, AJ, LK, AK: None

Figures

Figure 1.
Figure 1.
Enrollment and Inclusion of Patients
Figure 2.
Figure 2.
Receiver Operating Characteristics for Outcome of PPI Cessation Intervention.
Figure 3.
Figure 3.
Ability to Discontinue PPI Based on Number of Days with Elevated Acid Exposure.
Figure 4.
Figure 4.
Agreement Between Reflux Monitoring and Outcome of PPI Cessation
Figure 5.
Figure 5.
Patient Reported RESQ-eD Scores Throughout PPI Cessation Intervention
Figure 6.
Figure 6.
Conceptual Paradigm of Diagnostic Evaluation and Management for Patients with GERD Symptoms and Inadequate Symptom Response to PPI Therapy
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