INTRAVENOUS PROTON PUMP INHIBITOR (PPI) THERAPY AND EARLY HEARTBURN SYMPTOM RELIEF IN PATIENTS WITH GERD

Abstract

Purpose: There are limited data on heartburn symptom relief during first 4 h of therapy with acid-inhibiting drugs. This study investigated symptom relief over this period in subjects receiving i.v. omeprazole, which rapidly increases pH to >6 in fasting subjects, after a provocative meal. Methods: A single-centre, double-blind, randomized, 2-way cross-over study was conducted. Patients with macroscopically abnormal esophageal mucosa were excluded. At first visit, eligible patients (n = 75) were given a provocative meal (hamburger and fries, coca cola, coffee and mint chocolates); those developing at least moderate heartburn within 3 h were given placebo as i.v. bolus followed by continuous infusion for 4 h. To exclude placebo responders, those who experienced complete sustained symptom relief within 30 min were withdrawn. After 7-day washout, those remaining were randomized to receive either active treatment or placebo, and given a provocative meal (visit 2). At first perception of heartburn, patients received either omeprazole 80 mg or placebo (30 min bolus) followed by i.v. infusion of omeprazole 8 mg/h or placebo for 3.5 h. Patients graded symptoms according to Treatment Satisfaction Scale (TSQ), a 5-point Likert scale, every 15 minutes for 4 h. At visit 3, following 7-day washout the intervention was repeated. Adverse events were reported at follow-up, within 2–9 days of visit 3. Results: Thirty eight patients were randomized to placebo/omeprazole and 37 to omeprazole/placebo. Of these, 32 and 35, respectively were included in a per protocol analysis. Mean severity of heartburn during the 4-h treatment period was significantly lower (P <0.001) with omeprazole (2.5; 95% CI 2.3, 2.7) than placebo (2.7, 95% CI, 2.5, 2.9). However, over the 4-h period, no statistically significant differences were observed between omeprazole and placebo, with respect to maximum severity, sustained relief or complete resolution of heartburn. The i.v. omeprazole dose regimen was well-tolerated. Few adverse events were reported, and none were considered serious by the investigator. Conclusions: In a 4-h period after a provocative meal, i.v. omeprazole reduced the severity of meal-induced heartburn. However, overall differences observed between the two treatments were small, and their clinical relevance uncertain.