EFFECT OF OMEPRAZOLE ON THE OUTCOME OF ENDOSCOPICALLY TREATED BLEEDING PEPTIC-ULCERS - RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED MULTICENTER STUDY

Background: Haemostasis is highly pH-dependent and severely impaired a t low pH. However, there is no clear evidence that acid-suppressing dr ugs have beneficial effects in peptic ulcer haemorrhage. Endoscopic ha emostatic treatment provides important reduction in morbidity and may be more efficient when a neutral intragastric pH is maintained. Method s: We conducted a double-blind, placebo-controlled multicentre study o f intravenous infusion of omeprazole (80 mg as bolus, followed by 8 mg /h) or placebo for 72 h. All patients received 20 mg omeprazole orally from day 3 until follow-up on day 21. Only patients with ulcer haemor rhage, endoscoped within 12 h after admission, and with a history or s igns of circulatory failure and spurting bleeding, oozing bleeding, vi sible vessel, or clot, were included. Endoscopic intervention was aime d at when spurting bleeding, oozing bleeding, or a visible vessel was observed. The primary efficacy measure was the worst ranking on an ove rall outcome scale (5=death, 4=surgery, 3=additional endoscopic treatm ent, 2=more than 3 units of blood, and 1=no more than 3 units of blood transfused). Base-line prognostic factors of treatment success by day 3 and of other binary outcomes were considered in a logistic regressi on model. Results: Two hundred and seventy-four patients were randomly assigned to omeprazole (134 patients) or placebo (140 patients). The number of patients included in the 'intention-to-treat' analysis was 1 30 in the omeprazole group and 135 in the placebo group. The primary v ariable, the overall outcome at 72 h, showed a difference (P=0.004) be tween the two treatments in favour of omeprazole. Treatment success by 72 h defined as no death, no operation, or no additional endoscopic t reatment was 91.0% in the omeprazole group and 79.7% in the placebo gr oup (therapeutic gain, 11.3 percentage units; 95% confidence interval, 2.3 to 20.4 percentage units). Significant differences in favour of o meprazole were also found for secondary variables such as number of bl ood transfusions, duration and degree of bleeding, and the need for su rgery and additional endoscopic treatments on day 3 and day 21. Howeve r, the numbers of deaths by day 3, 21, or 35 were very similar. Conclu sions: We found a beneficial effect of intravenous omeprazole in sever e ulcer haemorrhage, with a reduction in the number of operations, in endoscopic treatments, and in the duration and severity of bleeding.