Levy 1997.

Methods	Open‐label randomised controlled trial
Participants	Baseline characteristics Number randomised: 70 participants Number analysed: 67 participants Ranitidine Age (years; mean (SD)): 56.9 (17.5) Number of participants (n): 35 Gender (male/female; n): 20/15 Omeprazole Age (years; mean (SD)): 57.3 (23.5) Number of participants (n): 35 Gender (male/female; n): 17/18 Inclusion criteria Affected by at least 1 of 9 risk factors regarded as strong indications for stress ulcer prophylaxis: burns, coagulopathy, acute hepatic failure, major neurologic insult, acute renal failure, respiratory failure, sepsis, shock, and trauma Acute Physiologic and Chronic Health Evaluation (APACHE II) scores were calculated at baseline Exclusion criteria Age < 18 years Pregnancy Admitted for a gastrointestinal haemorrhage Contraindication to the use of 5.enteral medications Admitted to the ICU more than 24 hours before identification for enrolment Baseline imbalances: Quote: "There were no statistically significant differences between the ranitidine‐treated and the omeprazole‐treated groups for age, gender, race, or APACHE II scores. Ranitidine subjects had significantly more risk factors at baseline. There were no significant differences in the number of patients who required mechanical ventilation: ranitidine, 26/35 (72%) and omeprazole 16/32 (50%)" Comment: More participants in the ranitidine group had major neurological insults or trauma. 7 and 5 participants in both groups had coagulopathy at baseline
Interventions	Ranitidine Dose (total/d): 150 mg Duration of treatment (days): ‐ Route: IV Intervention: ranitidine‐primed infusion 50‐mg bolus followed by 150 mg daily by continuous intravenous infusion or bolus administration 50 mg intravenously every 8 hours. In patients with renal insufficiency, the ranitidine dose was adjusted on the basis of the manufacturer’s recommendation Concomitant medications: ‐ Omeprazole Dose (total/d): 40 mg Duration of treatment (days): ‐ Route: PO or NG tube Intervention: 40 mg once daily orally or by nasogastric tube, if clinically necessary. If given by nasogastric tube, the omeprazole capsule was opened but the enteric‐coated granules were not crushed, so as to preserve delayed‐release activity. The 40‐mg dose of omeprazole was selected on the basis of its pharmacokinetics, and because it is a dose comparable with that used in related disorders Concomitant medications: ‐ Adherence to regimen: "Seventy patients formed the study group. Thirty five were randomised to the ranitidine treatment group, 35 received omeprazole. Three omeprazole subjects were excluded from data analysis because of errors in randomisation or enrolment criteria protocol violations, resulting in 32 omeprazole‐treated patients included in the final analysis" Duration of trial: over a 10‐month period Duration of follow up: ‐
Outcomes	Outcomes sought in review and reported in trial Primary outcomes Clinically important bleeding, haemodynamic instability resulting from gross bleeding as manifest by haematemesis, aspiration of 'coffee ground' material from the nasogastric tube, or melena. Clinically important bleeding was also defined by a decrease in haemoglobin > 2 g/dL complicated by the need for transfusion or haemodynamic instability. The haemoglobin value obtained 24 hours after admission was used as the baseline to allow for initial fluid equilibration. Oesophagogastroduodenoscopy was done only if deemed clinically indicated by the attending physician Secondary outcomes Nosocomial pneumonia as clinically diagnosed Duration of ventilation Duration of ICU stay All‐cause mortality in ICU Outcomes sought but not reported in trial All‐cause mortality in hospital Adverse events Participants requiring blood transfusion Units of blood transfused Outcomes reported in trial but not used in review Nil
Notes	Setting: New Hanover Regional Medical Center and the Coastal AHEC, Wilmington, North Carolina, and Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: Quote: "This study was approved by the Institutional Review Board" Informed consent: Quote: "...informed consent was obtained from each patient or their legally authorized representative" Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: Mortality was related to increased APACHE II scores. Endoscopy was performed on 27 participants (ranitidine 15 and omeprazole 15) and stress ulcers were detected in all but 2 participants (from each group). The source of bleeding in these participants could not be determined, but it was presumed to be due to stress ulcerations
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: not clearly mentioned in the study report
Allocation concealment (selection bias)	Unclear risk	Comment: not clearly mentioned in the study report
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: This was not a placebo‐controlled trial, and the different modes of administering study interventions would not have made it possible to blind study personnel and participants. Therefore, high risk of performance bias
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: unclear on blinding of outcome assessors. GI bleeding was detected as per the definition in the study protocol
Blinding (detection bias) Nosocomial pneumonia	High risk	Comment: unclear on blinding of outcome assessors. The definition of nosocomial pneumonia is not clearly mentioned in the study report
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: unclear on blinding of outcome assessors. However, owing to the objective nature of the outcomes of interest, the likelihood of detection bias is low
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comments: Three participants (from the omeprazole group) were not part of the final analysis for legitimate reasons such as errors in randomisation or enrolment criteria protocol violations. However, we did an intention‐to‐treat analysis
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported
Other bias	High risk	Comment: Source of funding was not clearly mentioned in the study report. Baseline differences between groups were detected