Randomised clinical trial: a novel rabeprazole extended release 50 mg formulation vs. esomeprazole 40 mg in healing of moderate‐to‐severe erosive oesophagitis – the results of two double‐blind studies

Aliment Pharmacol Ther 2011; 33: 203–212 Summary Background  Current PPIs may not achieve desired outcomes in some GERD patients due to limited duration of acid inhibition. Aim  To evaluate a novel rabeprazole extended release (ER), which provides longer duration of drug exposure and acid suppression, in healing and symptomatic resolution of moderate‐severe erosive oesophagitis. Methods  Patients with LA grade C or D oesophagitis were randomised to rabeprazole‐ER 50 mg or esomeprazole 40 mg once daily in two identical 8‐week double‐blind trials ( N  = 2130). Two primary endpoints were tested sequentially: (1) healing by 8 weeks [hypothesis: rabeprazole‐ER non‐inferior to esomeprazole (non‐inferiority margin = 8%)], (2) healing by 4 weeks [hypothesis: rabeprazole‐ER superior to esomeprazole ( P  < 0.05)]. The secondary endpoint was sustained heartburn resolution at 4 weeks. Results  Rabeprazole‐ER was non‐inferior to esomeprazole in week‐8 healing (80.0% vs. 75.0%; 77.5% vs. 78.4%). Week‐4 healing (54.8% vs. 50.3%; 50.9% vs. 50.7%) and sustained heartburn resolution (48.3% vs. 48.2%; 53.2% vs. 52.5%) were not significantly different. Post hoc combined results for grade D revealed rabeprazole‐ER vs. esomeprazole differences in week‐8 healing = 10.4% (95% CI: −1.4%, 22.2%) and week‐4 healing = 12.0% ( P  = 0.048). Conclusions  Rabeprazole‐ER is as effective as esomeprazole in healing moderate‐severe oesophagitis and achieves similar rates of heartburn resolution. Subgroup analysis suggests the possibility of benefit in severe oesophagitis, but this requires further evaluation (ClinicalTrials.gov: NCT00658528 and NCT00658775).