Cannon 1987.

Methods	Open‐label randomised controlled trial
Participants	Baseline characteristics Number randomised: 62 participants Number analysed: 59 participants Cimetidine Age (years; mean (SD)): 63.57 (2.86) Number of participants (n): 21 Gender (male/female; n): ‐ Antacids Age (years; mean (SD)): 58.56 (13.80) Number of participants (n): 19 Gender (male/female; n): ‐ Sucralfate Age (years; mean (SD)): 61.41 (5.94) Number of participants (n): 19 Gender (male/female; n): ‐ Inclusion criteria Critically ill with acute (< 48 hours) respiratory failure defined by Alveolar‐to‐arterial oxygen tension difference ≥ 350 mmHg Vital capacity < 10 cc/kg of body weight Alveolar hypoventilation with arterial pH < 7.25 or a ratio of dead space to tidal volume > 60% Exclusion criteria Allergy to cimetidine antacids, sucralfate Active gastrointestinal tract bleeding or guaiac‐positive stool Pregnancy or lactation Age < 18 or > 80 years Requiring dialysis Known bleeding diathesis Ventilator dependence for longer than 48 hours before the protocol was initiated GI tract surgery in the previous 48 hours Baseline imbalances: The 3 groups were almost similar with respect to age, gender, number of participants, and risk factors thought to precipitate GI bleed. Most participants were medical participants with respiratory failure secondary to an intrathoracic process. There was no significant difference between groups with respect to major risk factors for GI bleeding (sepsis, peritonitis, jaundice, hypotension, and trauma). Only acute renal failure was more common with the antacid regimen than with cimetidine and sucralfate (however, the incidence of renal failure did not correlate with upper GI bleed)
Interventions	Cimetidine Dose (total/d): 1200 mg Duration of treatment (days; mean (SE)): 123.69 (24.24) Route: IV Intervention: cimetidine initial dose of 300 mg given intravenously every 6 hours; if serum creatinine level was > 2.0 mg/dL, the dosing interval was changed to every 12 hours Concomitant medications: enteral nutrition in 22 participants from the overall study population; intervention group unclear; intravenous aminophylline was administered to 5 patients in the cimetidine group Antacids Dose (total/d): min 30 mL, max 120 mL Duration of treatment (days; mean (SD)): 115.25 (45.41) Route: NG tube Intervention: 30 mL of a commercial antacid, per nasogastric tube; if pH was > 4, the same dose was continued, or the dose given previously was doubled to reach a maximum of 120 mL Concomitant medications: enteral nutrition in 22 participants from the overall study population; intervention group unclear; intravenous aminophylline was administered to 4 patients in the cimetidine group Sucralfate Dose (total/d): 120 mL Duration of treatment (days; mean (SD)): 91.22 (24.01) Route: NG tube Intervention: 30 mL dissolved in warm tap water via nasogastric tube every 6 hours Concomitant medications: enteral nutrition in 22 participants from the overall study population; intervention group unclear,;intravenous aminophylline was administered to 6 participants in the cimetidine group Adherence to regimen: sucralfate, H2 receptor antagonists, or antacids were used inadvertently in 3 patients who were excluded from the trial Duration of trial: October 1985 to January 1986 Duration of follow‐up: 24 hours after extubation
Outcomes	Outcomes sought in review and reported in trial Clinically important upper GI bleeding defined as having frank blood or 'coffee ground' aspirate with a uniformly blue reaction by pH‐corrected indicator paper for occult blood All‐cause mortality in ICU Duration of intubation Adverse events of interventions Outcomes sought but not reported in trial report VAP All‐cause mortality in hospital Duration of intubation Duration of ICU stay Number of participants requiring blood transfusion Outcomes reported in report but not sought in review Gastric pH values Cost effectiveness
Notes	Setting: Medical‐Surgical Intensive Care Unit at Akron General Medical Centre, Ohio, USA Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: Quote: "The study was approved by the institutional review board at the Akron General Medical Centre" Informed consent: Quote: "A signed consent was obtained from patients or the next of kin after the potential complications and nature of the procedure were explained" Clinical trials registration: ‐ Sample size calculation: ‐
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Sixty‐two patients were accepted for computerised randomised study between October 1985 and January 1986" Comment: Method adopted to obtain random sequence generation is clearly mentioned in the trial report
Allocation concealment (selection bias)	Unclear risk	Comment: no information on allocation concealment reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: This was not a placebo‐controlled trial, and mode of administration of drugs could not have allowed blinding of participants and personnel involved in the trial
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: unclear if outcome assessors were blinded. However, GI bleeding was an objective outcome, which was detected as per the definition in the trial protocol
Blinding (detection bias) Nosocomial pneumonia	Unclear risk	Comment: The trial did not address this outcome
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Unclear risk	Comment: not enough information on criteria for diagnosis of other outcomes described
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Of the 62 patients originally entered into the study three were excluded because of the inadvertent concomitant use of sucralfate, H2 receptor antagonists or antacids in the study group" Comment: Groups to which these 3 participants belonged are unclear (ITT cannot be performed). These participants were excluded from the final analysis. Because loss to follow‐up was < 10% and appeared to be balanced across groups, this would not have introduced any attrition bias into the trial
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported
Other bias	Low risk	Comment: Source of funding is not clearly mentioned in the trial report. No other form of bias is detected