Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients

Steven A. Conrad, Andrea Gabrielli, Benjamin Margolis, Andrew Quartin, J. Steven Hata, William O. Frank, Robert G. Bagin, James A. Rock, Bonnie Hepburn, Loren Laine

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Objective: To demonstrate that a new immediate-release omeprazole oral suspension is effective in preventing upper gastrointestinal bleeding in critically ill patients. Design: 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. Setting: A total of 47 intensive care units in the United States. Patients: A total of 359 critically ill patients who required mechanical ventilation for ≥48 hrs, had an Acute Physiology and Chronic Health Evaluation score of ≥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. Interventions: 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 ≤ 4). Measurements and Main 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 ≥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 non-inferiority of omeprazole suspension. Median gastric pH was ≥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.

Original languageEnglish
Pages (from-to)760-765
Number of pages6
JournalCritical Care Medicine
Volume33
Issue number4
DOIs
StatePublished - Apr 1 2005

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Omeprazole
Cimetidine
Critical Illness
Suspensions
Hemorrhage
Stomach
Therapeutic Irrigation
APACHE
Coffee
Therapeutics
Artificial Respiration
Intensive Care Units
Population

Keywords

  • Cimetidine
  • Gastrointestinal bleeding
  • Mechanical ventilation
  • Nosocomial pneumonia
  • Omeprazole

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. / Conrad, Steven A.; Gabrielli, Andrea; Margolis, Benjamin; Quartin, Andrew; Hata, J. Steven; Frank, William O.; Bagin, Robert G.; Rock, James A.; Hepburn, Bonnie; Laine, Loren.

In: Critical Care Medicine, Vol. 33, No. 4, 01.04.2005, p. 760-765.

Research output: Contribution to journalArticle

Conrad, Steven A. ; Gabrielli, Andrea ; Margolis, Benjamin ; Quartin, Andrew ; Hata, J. Steven ; Frank, William O. ; Bagin, Robert G. ; Rock, James A. ; Hepburn, Bonnie ; Laine, Loren. / Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. In: Critical Care Medicine. 2005 ; Vol. 33, No. 4. pp. 760-765.
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AU - Margolis, Benjamin

AU - Quartin, Andrew

AU - Hata, J. Steven

AU - Frank, William O.

AU - Bagin, Robert G.

AU - Rock, James A.

AU - Hepburn, Bonnie

AU - Laine, Loren

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N2 - Objective: To demonstrate that a new immediate-release omeprazole oral suspension is effective in preventing upper gastrointestinal bleeding in critically ill patients. Design: 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. Setting: A total of 47 intensive care units in the United States. Patients: A total of 359 critically ill patients who required mechanical ventilation for ≥48 hrs, had an Acute Physiology and Chronic Health Evaluation score of ≥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. Interventions: 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 ≤ 4). Measurements and Main 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 ≥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 non-inferiority of omeprazole suspension. Median gastric pH was ≥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.

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KW - Cimetidine

KW - Gastrointestinal bleeding

KW - Mechanical ventilation

KW - Nosocomial pneumonia

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