Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients.
OBJECTIVE
To demonstrate that a new immediate-release omeprazole oral suspension is effective in preventing upper gastrointestinal bleeding in critically ill patients.


METHODS
A noninferiority analysis was used to compare rates of clinically significant upper gastrointestinal bleeding in a prospective, phase 3, double-blind trial with parallel omeprazole suspension and cimetidine treatment groups.


METHODS
A total of 47 intensive care units in the United States.


METHODS
A total of 359 critically ill patients who required mechanical ventilation for > or =48 hrs, had an Acute Physiology and Chronic Health Evaluation score of > or =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.


METHODS
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/hr thereafter) for up to 14 days. Gastric aspirates were sampled for bleeding and pH. Medication doses were doubled for failure of pH control (two successive aspirates with pH < or = 4).


RESULTS
Clinically significant upper gastrointestinal bleeding (bright red blood not clearing after 5-10 mins of lavage or persistent Gastroccult-positive "coffee-grounds" material for 8 hrs on days 1-2 or for 2-4 hrs on days 3-14 and not clearing with > or =100 mL of lavage) was the primary end point of the trial. The rate of clinically significant bleeding in the per-protocol population was 4.5% with omeprazole suspension and 6.8% with cimetidine, meeting the criteria for the noninferiority of omeprazole suspension. Median gastric pH was > or =6 on all trial days with omeprazole suspension treatment and on 50% of days with cimetidine treatment (p < .001, all trial days). In the omeprazole suspension group, median gastric pH was >4 on each trial day in 95% of patients.


CONCLUSIONS
Immediate-release omeprazole suspension is effective in preventing upper gastrointestinal bleeding and more effective than intravenous cimetidine in maintaining gastric pH of >4 in critically ill patients.
Conrad
Steven A
SA
Louisiana State University, Shreveport, LA, USA.
Gabrielli
Andrea
A
Margolis
Benjamin
B
Quartin
Andrew
A
Hata
J Steven
JS
Frank
William O
WO
Bagin
Robert G
RG
Rock
James A
JA
Hepburn
Bonnie
B
Laine
Loren
L
D000284:Administration, Oral; D000368:Aged; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D002927:Cimetidine / Q000008:administration & dosage*; D003422:Critical Care / Q000379:methods*; D004304:Dosage Forms; D004311:Double-Blind Method; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage*; D013270:Stomach / Q000503:physiopathology; D016019:Survival Analysis; D013535:Suspensions; D016896:Treatment Outcome
D000897:Anti-Ulcer Agents; D004304:Dosage Forms; D013535:Suspensions; D002927:Cimetidine; D009853:Omeprazole