Lacroix 1986.

Methods	Parallel‐group randomised controlled trial
Participants	Baseline characteristics Number randomised: 40 participants Number analysed: 38 participants Cimetidine Age (years; mean (SE)): 1.59 (3.0) Number of participants (n): 19 Gender (male/female; n): 7/12 Placebo Age (years; mean (SE)): 2.13 (3.4) Number of participants (n): 21 Gender (male/female; n): 8/13 Inclusion criteria All children from birth to 18 years of age Admitted to the PICU with illness that precludes any oral or enteral nutrition for at least 2 days Exclusion criteria Admission to the PICU more than 24 hours previously Burns or surgical problems Weight < 2.5 kg Admission because of GI tract bleeding Need for oral or enteral feeding Congenital cardiac disease Creatinine > 3 mg/dL Renal failure or cerebral death Intoxication in which the toxic substances ingested could interact with cimetidine Treatment requiring administration of cimetidine, antacids, anticoagulants, or theophylline, or dialysis Baseline imbalances: Mechanical ventilation was used in 2 times more patients in the placebo group
Interventions	Cimetidine Dose (total/d): 0.13 mL/kg (20 mg/kg), up to a maximum of 6.66 mL/d (1000 mg/d) Duration of treatment (days): 10 Route: IV Intervention: Ampules for intravenous injection of drug contained 2 mL solution of cimetidine at 150 mg/mL (300 mg per ampoule). Ampules were prepared and grouped so that all those used for 1 patient contained or did not contain cimetidine Concomitant medications: steroids, mechanical ventilation, blood transfusion in some Placebo Dose (total/d): same amount of placebo solution Duration of treatment (days): 10 Route: IV Intervention: Ampules for intravenous injection of drug contained 2 mL placebo solution. Ampules were prepared and grouped so that all those used for 1 patient contained or did not contain cimetidine Concomitant medications: steroids, mechanical ventilation, blood transfusion in some Adherence to treatment: ‐ Duration of trial: ‐ Duration of follow‐up (days): ‐
Outcomes	Outcomes sought in review and reported in trial Clinically important upper GI bleeding Number of participants requiring blood transfusions Outcome sought in review and not reported in trial VAP All‐cause mortality Duration of ICU stay Duration of intubation Adverse events of interventions Outcomes reported in trial and not sought in review Gastric pH Bleeding‐free survival
Notes	Setting: PICU, Department of Pediatrics, Pediatric intensive Care Unit, Hopital Sainte‐Justine, University of Montreal, Canada Sponsorship source: Smith Kline & French Laboratories Conflicts of interest: ‐ Ethics approval: Study was approved by the Ethics Committee of Hopital Sainte‐Justine Informed consent: Written informed consent was obtained from a parent or guardian of each patient Clinical trials registration: ‐ Sample size calculation: We calculated a necessary sample size of 37 participants
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "Allocation of treatment followed a double‐blind pattern, according to a list set up by the Smith Kline & French Laboratories from a table of random numbers" Judgement comment: list of random number set up by study sponsor. Some risk of bias suspected
Allocation concealment (selection bias)	Unclear risk	Quote: "Allocation of treatment followed a double‐blind pattern, according to a list set up by the Smith Kline & French Laboratories from a table of random numbers" Judgement comment: no details about allocation concealment reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Comment: "double‐blind pattern". Procedures for blinding not explicitly reported, but lack of blinding is unlikely to introduce bias to the outcomes or outcome measures
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Quote: "UGIB noted from the nasogastric tube, which had been inserted in each patient. Outcome was assessed by the appearance of UGIB and by gastric fluid pH. Massive UGIB was defined as red or brown haemorrhage from the nasogastric tube associated with a decrease in arterial blood pressure of >20 mm Hg or with an acute decrease in haemoglobin level of >2 gm/dl; obvious UGIB was defined as red or brown haemorrhage from the nasogastric tube without a decrease in arterial blood pressure or in haemoglobin level of >2 gm/dl; slight UGIB was defined as minimal bleeding appearing only at the aspiration of gastric fluid" Comment: criteria for diagnosis of this outcome reported objectively
Blinding (detection bias) Nosocomial pneumonia	Unclear risk	Comment: Study did not address this outcome
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Unclear risk	Comment: no details about blinding of outcome assessors reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: no incomplete outcome data suspected. All participants randomised at baseline were included in analyses
Selective reporting (reporting bias)	Low risk	Comment: All outcomes listed in the Methods section (GI bleeding) were also reported in the Results section
Other bias	High risk	Comment: Industry participates in providing drugs and conducting the trial. Mechanical ventilation (risk factor for GI bleeding) was used more often in placebo group