Ortiz 1998.

Methods	Open‐label randomised controlled trial
Participants	Baseline characteristics Number randomised: 78 participants Number analysed: 78 participants (for outcomes of interest to this review) Cimetidine bolus Age (years; mean (SD)): 62.2 (14.2) Number of participants (n): 14 Gender (male/female; n): 7/7 Cimetidine continuous Age (years; mean (SD)): 61.2 (18.8) Number of participants (n): 12 Gender (male/female; n): 6/6 Sucralfate Age (years; mean (SD)): 64.1 (18.8) Number of participants (n): 12 Gender (male/female; n): 5/7 No prophylaxis Age (years; mean (SD)): ‐ Number of participants (n): 26 Gender (male/female; n): ‐ Inclusion criteria Respiratory failure for which more than 72 hours of mechanical ventilation was expected Exclusion criteria Age < 18 years No nasogastric tube in place Prior gastric ablation and contraindication to stress ulcer prophylaxis Pneumonia or GI haemorrhage Baseline imbalances: Baseline characteristics for participants who met the criteria for early withdrawal from the study (for reasons mentioned below) are not mentioned. Nearly 40 participants were withdrawn from the study
Interventions	Cimetidine bolus Dose (total/d): 900 mg Duration of treatment (days): 7 days Route: IV Intervention: 300 mg by intravenous bolus every 8 hours Concomitant medications: antibiotics Cimetidine continuous Dose (total/d): 900 mg Duration of treatment (days): 7 days Route: IV Intervention: 900 mg by continuous intravenous infusion over 24 hours Concomitant medications: antibiotics Sucralfate Dose (total/d): 4 g Duration of treatment (days): 7 days Route: NG tube Intervention: 1 gram by NG tube every 6 hours Concomitant medications: antibiotics No prophylaxis Dose (total/d): ‐ Duration of treatment (days): ‐ Route: ‐ Intervention: gastric feeding Concomitant medications: antibiotics Adherence to regimen: Quote: "Patients who met criteria for early withdrawal (< 3 days) were not included in the final analysis" Comment: Withdrawal was mainly due to GI bleeding, gastric colonisation on entry, extubation, mortality, and inability to aspirate GI secretions and change to tube feedings Duration of trial: ‐ 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 (none of them were the primary outcomes in the study) Clinically significant upper GI bleeding defined as a continuous lavage of red blood from the nasogastric aspirate and the need for at least 1 unit of packed red blood cells. This was the definition followed for including/excluding participants. It can be assumed that this definition was followed later on as well during the course of the study and all participants detected with GI bleed required transfusion as well All‐cause mortality in ICU (within the first 3 days and later on) Participant requiring blood transfusions;It can be assumed that this definition was followed later on as well during the course of the study and all participants detected with GI bleed required transfusion from the definition above. Note to 1: Only those that occurred within the first 3 days and caused withdrawal were reported Outcomes sought but not reported in trial report Incidence of VAP Duration of ICU stay Units of blood transfused Adverse events if interventions Outcomes reported in report but not used in review Duration of intubation (mentioned for only participants who did not withdraw from the study) Gastric colonisation All‐cause mortality in hospital (overlap with ICU mortality suspected)
Notes	Setting: Department of Critical Care Medicine, Saint Vincent Hospital, Worcester, Massachusetts, and Department of Surgery, New England Medical Centre, Boston, Massachusetts Source of funding: Smith Kline Beecham, Inc., Philadelphia, Pennsylvania Informed consent: ‐ Ethics approval: Quote: "The study was approved by the institutional review board" Clinical trials registration: ‐ Sample size calculation: ‐ Comment: Power analysis has been done at the end of the study to detect a correlation of less than 0.4 Additional notes: Cimetidine arms were combined to form a common interventional arm as the review did not aim to investigate efficacy on the basis of dose or mode of administration in the same drug
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "All other patients were randomised (table of random numbers) into one of the three groups" 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 is an unblinded trial, and GI bleeding was detected as per the definition in the trial protocol
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 is an unblinded trial, and all other outcomes of interest were objective in nature
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: 40 randomised participants were withdrawn from the study (more than 50%) for protocol violations and were excluded from the final analysis. However, relevant data (for GI bleed, ICU mortality) could be obtained from the study
Selective reporting (reporting bias)	High risk	Comment: The duration of intubation,hospital mortality and participants requiring antibiotics are mentioned only for participants who were part of the final analysis, and this excluded earlier withdrawals. This accounts for selective reporting
Other bias	High risk	Comment: This study was supported by a grant from Smith Kline Beecham, and some of the equipment used was received from this organisation. However, the role of the sponsor in the conduct and reporting of the trial is unclear. Baseline characteristics for 40 participants (excluded owing to early withdrawal) are not mentioned in the study report