Groll 1986.

Methods	Double‐blind randomised placebo‐controlled trial
Participants	Baseline characteristics Number randomised: unclear on how many were initially randomised. Study report mentions that 531 participants were eligible for the trial, of whom 221 participants completed the trial with reasons for excluding of the remaining participants Number analysed: 221 participants Cimetidine Age (years; mean (range)): 58(16‐90) Number of participants (n): 114 Gender (male/female; n): 75/39 Placebo Age (years; mean (range)): 57 (15‐88) Number of participants (n): 107 Gender (male/female; n): 68/39 Inclusion criteria Admitted to Kingston General Hospital medical‐surgical ICU Exclusion criteria Participants who had bleeding on admission to the ICU Pregnancy Renal failure requiring haemodialysis or peritoneal dialysis Drug overdosage Acute myocardial infarction Use of antacids Stay in the unit was less than 24hours Inability to obtain early consent Refusal to enter the study Death within the first 24 hours Accidental omission by house staff Miscellaneous reasons Baseline imbalances: Quote: "The drug and placebo groups were similar for demographic features and risk factors.The number of patients with each risk factor known to predispose to stress ulceration and the mean number of risk factors per patient were similar in both groups such as minor operative procedure, respiratory failure, renal failure, sepsis, shock, trauma, coma and liver failure"
Interventions	Cimetidine Dose (total/d): 1200 mg Duration of treatment (days, mean (range)): 3.8 (1‐23 days) Route: IV Intervention: 300 mg in 20 mL normal saline given intravenously every 6 hours Concomitant medications: ‐ Placebo Dose (total/d): ‐ Duration of treatment (days, mean (range)): 3.6 (1‐20 days) Route: IV Intervention: prepared in an identical manner to cimetidine, given intravenously every 6 hours Concomitant medications Adherence to regimen: Quote: "Of the remaining 531 eligible patients 221 completed the trial (41%). The remainder were excluded because of inability to obtain early consent (n = 69), refusal to enter the study (n = 83), death within the first 24 hours (n = 48), accidental omission by house staff (n = 86), and miscellaneous reasons (n = 24)" Comment: not sure when randomisation took place and exact numbers of participants who were initially randomised Duration of trial: 21 months 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 Clinically important upper GI bleeding diagnosed as Frank haematemesis or gastric aspirate of > 50 mL fresh blood Malaena or fresh blood per rectum with an upper source of haemorrhage verified by endoscopy if the gastric aspirate was clear A fall in haemoglobin level > 2 g/dL in a 24‐hour period associated with either 4+ occult blood in the stools or 'coffee ground' gastric drainage of at least 100 mL. Upper gastrointestinal endoscopy was not a prerequisite for entry into the study, as its routine use was considered unwarranted in critically ill patients Note: Data were not provided separately for overt and occult bleeds. Of the 70% of participants who were in the study for 1 to 3 days, 9 of the 11 placebo and 5 of the 6 cimetidine participants bled All‐cause mortality in ICU Outcomes sought but not reported in trial VAP All‐cause mortality in hospital Duration of ICU stay Duration of Intubation Participants requiring blood transfusion Adverse events of interventions Outcomes reported in report but not used in review Volumes of packed cells administered (mean and ranges provided) Intragastric pH status Gastric colonisation
Notes	Setting: Kingston General Hospita, Ontario, Canada Source of funding: Quote: "This project was supported by Smith Kline and French Canada Ltd" Conflicts of interest: ‐ Ethics approval: Quote: "The study was approved by the Institutional Review Board and Grant agency at the Misnistry of Healthof Chez Republic" Informed consent: Quote: "The study was approved by the committee on human research, Department of Medicine, Queen's University" Clinical trials registration: ‐ Sample size calculation: ‐
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	Low risk	Quote: "Patients were randomised in a double blind method to receive injections of either cimetidine 300 mg in 20 mL normal saline or placebo prepared in an identical manner, given intravenously every 6 hours" Comment: This was a placebo‐controlled trial, and participants and personnel were blinded
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Quote: "Patients were randomised in a double blind method to receive injections of either cimetidine 300 mg in 20 mL normal saline or placebo prepared in an identical manner, given intravenously every 6 hours" Comment: This was a placebo‐controlled trial, and GI bleeding was detected as per the definition in the study owing to the objective nature of the outcome of interest
Blinding (detection bias) Nosocomial pneumonia	Unclear risk	Comment: Study did not address this outcome
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: This was a placebo‐controlled trial, and participants and personnel were blinded. Moreover owing to the objective nature of the outcomes of interest, the likelihood of detection bias is low
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote: "Of the remaining 531 eligible patients 221 completed the trial (41%). The remainder were excluded because of inability to obtain early consent (n = 69), refusal to enter the study (n = 83), death within the first 24 hours (n = 48), accidental omission by house staff (n = 86), and miscellaneous reasons (n = 24)" Comment: not sure when randomisation took place and exact numbers of participants who were initially randomised. Therefore unclear on attrition bias
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported
Other bias	Low risk	Comment: This project was supported by Smith Kline and French Canada Ltd. The role of the sponsor in the conduct and reporting of the trial is unclear. No other sources of bias suspected