Global 
Deutschland Esophagus to Small Intestine
Clin Gastroenterol Hepatol. 2025;23(13):2459-2467
pH impedance monitoring on proton pump inhibitor therapy impacts management decisions in proven GERD but not in unproven GERD
Background and aims: Ambulatory reflux monitoring off proton pump inhibitors (PPIs) is useful in unproven gastroesophageal reflux disease (GERD). In this prospective clinical trial, the authors evaluated if on-PPI pH-impedance monitoring provides value in unproven GERD.
Methods: Patients with typical reflux symptoms with incomplete PPI response were studied both off-PPI (wireless pH monitoring) and on-PPI (pH-impedance monitoring) at two tertiary care centers. Patients and investigators were blinded to reflux testing findings, and patients were asked to self-resume PPI for uncontrolled symptoms despite rescue antacids. Data analysis determined if on-PPI pH-impedance findings correlated with off-PPI acid exposure time (AET) or influenced PPI-related decision making.
Results: Of 79 patients, all 26 (32.9%) with refractory GERD metrics on-PPI had proven GERD off-PPI. In 60 patients with proven GERD off-PPI, 56.7% had no ongoing GERD on-PPI. No on-PPI pH-impedance findings predicted PPI decision making among conclusive, borderline, or no reflux (p = 0.872); AET (p = 0.107); reflux episodes numbers (p = 0.113); mean nocturnal baseline impedance (p = 0.621); and reflux-symptom association categories (p = 0.363). In multivariable linear and logistic regression models, off-PPI AET modestly predicted refractory GERD (odds ratio [OR] = 1.34; 95% confidence interval [CI]: 1.11–1.63; p = 0.003), and reflux episode numbers were borderline in predicting conclusive GERD off-PPI (OR = 1.00; 95% CI: 1.00–1.10; p = 0.04).
Conclusions: A minority of symptomatic patients will have refractory GERD evidence on pH-impedance monitoring on PPI; this strategy risks missing over half of the cohort with proven GERD if testing off-PPI is unavailable. These findings support documenting GERD off-PPI first in PPI nonresponders and restricting on-PPI pH-impedance monitoring to identify refractory GERD only in patients with proven GERD with persisting symptoms.