Solouki 2009.

Methods	Double‐blind randomised controlled trial
Participants	Baseline characteristics Number randomised: 129 participants Number analysed: 129 participants Ranitidine Age (years; mean (range)): 49.19 (5 ‐ 85) Number of participants (n): 68 Gender (male/female; n): 35/33 Omeprazole Age (years; mean (range)): 52.41 (5 ‐ 95) Number of participants (n): 61 Gender (male/female; n): 32/29 Inclusion criteria Admitted to ICU Under mechanical ventilation for a minimum of 48 hours Nasogastric tube in place, which would help to monitor and confirm the upper GI bleedings, if it occurred Exclusion criteria Induviduals with Pneumonia Current upper GI bleeding Previous gastrectomy Current usage of 2 doses of prophylaxis Transported from another ICU ward Baseline imbalances: Patients’ age in group A ranged from 5 to 85 years with mean age of 49.19 years. Group B patients were in the age range of 5 to 95 years with mean age of 52.41 years. In the omeprazole group. There were 32 (52.5%) males and 29 (47.5%) females. These numbers were 35 (51.5%) males and 33 (48.5%) females in the ranitidine group. The 2 groups were similar with respect to the baseline risk factors responsible for GI bleeding
Interventions	Ranitidine Dose (total/d): 100 mg Duration of treatment (days): ‐ Route: IV Intervention: Intravenous ranitidine was used with 50‐mg dosage 2 times a day accompanied by placebo gavages through nasogastric tube Concomitant medications: corticosteroids and antibiotics, intermittent nasogastric feeding (300 to 400 mL, 4‐hourly) Omeprazole Dose (total/d): 40 mL Duration of treatment (days): ‐ Route: NG tube Intervention: 20 mL of a suspension of omeprazole 2 times a day was gavaged in addition to 2 cc of a parenteral placebo drug Concomitant medications: corticosteroids and antibiotics, intermittent nasogastric feeding (300 to 400 mL 4‐hourly) Adherence to regimen: 128 participants were randomised to receive 2 interventions; Ranitidine + Placebo (68) and Omeprazole + Placebo (61). 12 participants died in the first group while 3 died in the second group Duration of trial: June 2000 to January 2001 Duration of follow up: not clearly mentioned in the study report. Probably until death or discharge
Outcomes	Outcomes sought in review and reported in trial Primary outcome Incidence of GI bleeding: 2 types of GI bleeding including overt and clinically important bleedings were evaluated in this study. If 1 of the following happens, the situation is called “overt GI bleeding”: haematemesis, 'coffee ground' in NGT, melena, or haematochezia. Overt bleeding in addition to at least 1 of the following items is called “clinically important GI bleeding”: 20 mmHg decrease in systolic or diastolic blood pressure during the first 24 hours after bleeding 20 bpm increase in heart rate or 10 mmHg in systolic blood pressure in a standing position 2 g/dL decrease in Hb or 6% HCT during first 24 hours after bleeding Lack of increase in Hb after infusion of 2 units of packed cells Secondary outcomes Incidence of ventilator‐associated pneumonia defined as new infiltration in chest X‐ray along with 2 of the 3 following criteria: fever ≥ 38.3°C, leucocytosis ≥ 10,000, and pus in tracheal tube suction. Ultimate diagnosis was achieved by a positive culture of tracheal secretions. Existence of at least 105 colonies of pathogenic micro‐organisms was considered positive All‐cause mortality in ICU Duration of intubation Outcomes sought but not reported in trial All‐cause mortality in hospital Adverse drug reactions Participants requiring blood transfusions Units of blood transfused Outcomes reported but not used in review Nil
Notes	Setting: Department of Internal Medicine and Intensive Care Unit, Imam Hossein Hospital, Shahid Beheshti University, M.C., Tehran, Iran Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: Quote: "The study was approved by the institutional ethics committee..." Informed consent: Quote: "Written consents signed by the patients or their family members were obtained for participation in the study" Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: In the ranitidine group, 4 in 14 participants who had overt bleeding had clinically important GI bleeding. This was 1 in 3 participants from omeprazole group
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Using the table numbers randomly, all ICU beds were divided into two groups of A and B" Comment: Method adopted to obtain random sequence generation is 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
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: This was a randomised double‐blind placebo‐controlled trial, and outcome assessors appeared to be blinded. GI bleeding was an objective outcome detected as per the definition in the study protocol
Blinding (detection bias) Nosocomial pneumonia	Low risk	Comment: This was a randomised double‐blind placebo‐controlled trial, and outcome assessors appeared to be blinded. VAP was an objective outcome detected as per the definition in the study protocol
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: This was a randomised double‐blind controlled trial, and outcome assessors seem to be blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: All randomised participants were part of the final analysis
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported
Other bias	Low risk	Comment: Source of funding not known. No other known source of bias