Peura 1985.

Methods	Double‐blind randomised placebo‐controlled trial
Participants	Baseline characteristics Number randomised: 39 participants Number analysed: 39 participants Cimetidine Age (years; mean (SD)): 61.2 (17.8) Number of participants (n): 21 Gender (male/female; n):15/6 Placebo Age (years; mean (SD)): 51.1 (18.2) Number of participants (n): 18 Gender (male/female; n): 13/5 Inclusion criteria All patients admitted to medical ICU with an illness of sufficient severity to expect a minimum of 5 days care in the unit Exclusion criteria Age < 18 years Presence of acute myocardial infraction Pregnancy Prior gastric surgery Contraindications to upper gastrointestinal endoscopy Clinical evidence of active or recent GI bleeding, such as hematemesis, melena, haemoccult positive stools, or nasogastric aspirate Baseline imbalances: Quote: "The treatment groups were similar in the number of patients, sex and severity of illness as determined by the primary diagnosis. The cimetidine group tended to be older, but this difference was not statistically significant. Both treatment arms were also similar in the initial pretreatment endoscopic classification" Comment: The 2 groups appear to be similar in their demographic and other characteristics, suggesting no imbalance between the 2 at baseline. Mosg in both groups were diagnosed with cardiopulmonary disease
Interventions	Cimetidine Dose (total/d): 1200 mg Duration of treatment (days): 3 to 14; treatment was stopped when the participant was transferred from the ICU Route: IV Intervention: 300 mg intravenously every 6 hours Concomitant medications: Quote :"Medical management of patients in the study was standard as their underlying conditions allowed" Comment: The specific names of medications administered were not mentioned. It seems that almost all participants were on oral feeding when their condition was stable. Partcipants with compromised renal function received cimetidine or placebo every 8 to 12 hours rather than every 6 hours. Use of ulcerogenic drugs (salicylates, NSAIDs) and antacids was not permitted according to the study protocol Placebo Dose (total/d): ‐ Duration of treatment (days): 3 to 14; treatment was stopped when the participant was transferred from the ICU Route: IV Intervention: IV injection of placebo every 6 hours Concomitant medications: Quote :"Primary treatment of the admitting diagnosis as was the medical management of patients in the study was standard as their underlying conditions allowed" Comment: The specific names of medications administered were not mentioned. It seems that almost all participants were on oral feeding when their condition was stable. Partcipants with compromised renal function received cimetidine or placebo every 8 to 12 hours rather than every 6 hours. Use of ulcerogenic drugs (salicylates, NSAIDs) and antacids was not permitted according to the study protocol Adherence to regimen: ‐ Duration of trial: ‐ Duration of follow‐up: not clearly mentioned in the study report. Probably until death or discharge from the hospital
Outcomes	Outcomes sought in review and reported in trial Primary outcome Incidence of GI bleeding (mucosal anomalities were determined endoscopically and the incidence of bleeding, thus determined can be considered as primary outcome) Secondary outcomes All‐cause mortality in ICU Adverse events of interventions Outcomes sought but not reported in trial report Incidence of ventilator‐associated pneumonia All‐cause mortality in hospital Duration of intubation Duration of ICU stay Outcomes reported but not used in review Number of participants requiring blood transfusions (not clear whether it is due to persisting bleeding or newly developed bleed) Units of blood transfused (not clear whether it was in participants with persisting bleeding or newly developed bleed) Gastro duodenal mucosal examination through endoscopy
Notes	Setting: Gastroenterology Service, Department of Medicine, Walter Reed Army Medical Center, Washington, DC Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: Quote: "This protocol was approved by the Clinical Investigation and Human Use Committees of the Walter Reed Army Medical Center" Informed consent: Quote: "Each patient or guardian gave informed consent" Clinical trials registration: not provided in the study report Sample size calculation: ‐ Additional notes: On initial endoscopy, it was found that there were endoscopic signs of bleeding in 14 of 29 participants with mucosal abnormalities. 3 participants from the placebo arm developed new signs of bleeding during the study, when serial endoscopy was done. One death in the placebo group was attributed to upper GI bleed
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: “The group not receiving cimetidine received an intravenous injection of placebo every 6 hours to ensure the double blind nature of the study” Comment: This suggests that participants and personnel were blinded to the interventions
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Quote: "All endoscopic examinations were done by a single investigator and witnessed by a second investigator who observed the procedure through a lecturescope. During the endoscopy, findings were discussed and agreed on by both investigators before an entry was made on the report form. Both investigators were uninformed as to the patient’s treatment group" Comment: Outcome assessors were blinded. The definition for detecting GI bleed was not clearly mentioned. However, it was an objective outcome detected through endoscopy. Therefore the likelihood of performance or detection bias is low
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: All other outcomes of interest were objective in nature
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 reported and analysed in the study
Other bias	Low risk	Comment: unclear on the source of funding. No additional biases were detected