April 22, 2005 -- A new immediate-release oral omeprazole solution is not inferior to intravenous cimetidine to prevent upper gastrointestinal bleeding in critically ill patients, according to the results of a randomized trial published in the April 15 issue of Critical Care Medicine.
"Because they are rapidly degraded in an acidic environment, oral proton pump inhibitors are marketed as delayed-release formulations with enteric coatings, limiting their use in the critically ill population," write Steven A. Conrad, MD, PhD, from Louisiana State University in Shreveport, and colleagues. "Little information is available on the efficacy of proton pump inhibitors in the prophylaxis of bleeding in critically ill patients, and no double-blind, randomized, controlled trials have been published."
In this phase 3, double-blind, double-dummy trial taking place at 47 U.S. intensive care units, 359 critically ill patients were randomized to treatment with omeprazole suspension (two 40-mg doses on day 1, via orogastric or nasogastric tube, and 40 mg each day thereafter) or intravenous cimetidine (300-mg bolus and 50 mg/hour thereafter) for up to 14 days.
Participants had required mechanical ventilation for more than 48 hours, had an Acute Physiology and Chronic Health Evaluation score of greater than 11 at baseline, had an intact stomach with a nasogastric or orogastric tube in place, and had at least one additional risk factor for upper gastrointestinal bleeding. Gastric aspirates were sampled for bleeding and pH, and medication doses were doubled for failure of pH control, defined as two successive aspirates with pH less than 4.
The primary end point was clinically significant upper gastrointestinal bleeding, defined as bright red blood not clearing after five to 10 minutes of lavage; or persistent Gastroccult-positive "coffeegrounds" material for eight hours on days 1 to 2, or for two to four hours on days 3 to 14, not clearing with greater than 100 mL of lavage.
The primary end point occurred in 4.5% of the omeprazole group and in 6.8% of the cimetidine group, meeting criteria for the noninferiority of omeprazole suspension. Median gastric pH was greater than 6 on all trial days with omeprazole and on 50% of days with cimetidine ( P < .001 for all trial days). Median gastric pH was greater than 4 on each trial day in 95% of patients in the omeprazole group.
Study limitations include lack of power to assess the superiority of omeprazole suspension compared with intravenous cimetidine for preventing clinically significant upper gastrointestinal bleeding.
"Immediate-release omeprazole suspension is effective in preventing upper gastrointestinal bleeding in critically ill patients, and more effective than a continuous infusion of cimetidine in maintaining gastric pH of >4, without increasing the incidence of nosocomial pneumonia in patients requiring mechanical ventilation," the authors write.
Santarus, the maker of Zegerid, an oral formulation of omeprazole, supported this study and employs four of its authors.
Crit Care Med. 2005;33:760-765
Reviewed by Gary D. Vogin, MD
Medscape Medical News © 2005
Cite this: Laurie Barclay. Oral Omeprazole May Be Comparable to IV Cimetidine to Prevent Upper GI Bleeding - Medscape - Apr 22, 2005.