Background  A trial of empirical PPI therapy is usual practice for most patients with symptoms of gastro-oesophageal reflux disease (GERD) in primary care.

Aim  To determine if the 4-week efficacy of rabeprazole 20 mg for resolving heartburn and regurgitation symptoms is non-inferior to esomeprazole 40 mg or 20 mg.

Methods  In all, 1392 patients were randomized to rabeprazole 20 mg, esomeprazole 20 mg or 40 mg once daily. Patients, doctors and assessors were blinded. Symptom resolution data were collected on days 0–7 and day-28 using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index with a shortened version used on days 8–27.

Results  Rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete resolution of regurgitation and satisfactory resolution of heartburn and regurgitation. For complete heartburn resolution, the efficacy of rabeprazole 20 mg and esomeprazole 40 mg was statistically indistinguishable, although the non-inferiority test was inconclusive. Rabeprazole 20 mg was non-inferior to esomeprazole 20 mg for all outcomes.

Conclusions  In uninvestigated GERD patients, rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete and satisfactory relief of regurgitation and satisfactory relief of heartburn, and not different for complete resolution of heartburn.