Maier 1994.

Methods	Open‐label randomised controlled trial
Participants	Baseline characteristics Number randomised: 98 participants Number analysed: 98 participants Ranitidine Age (years; mean (SD)): 34.2 (13.3) Number of participants (n): 51 Gender (male/female; n): 37/14 Sucralfate Age (years; mean (SD)): 34.2 (16.4) Number of participants (n): 47 Gender (male/female; n): 39/8 Inclusion criteria Endotracheal intubation on admission with anticipation of at least 72 hours of ICU care before extubation Presence of NG tube at the time of admission Age > 18 years Exclusion criteria Early extubation Protocol violation Initiation of gastric feeding, Thrombocytopaenia Death Inability to obtain consent Baseline imbalances: The 2 groups were similar with respect to gender distribution, age, admission APACHE II scores, Injury Severity Score, Revised Trauma Score, and history of smoking. Overall, patterns of injury were also similar in both groups
Interventions	Ranitidine Dose (total/d): unclear Duration of treatment (days): 72 hours to until the participant was extubated or was fed via the stomach. Study patients were enrolled an average of 4.3 days Route: IV Intervention: hydrochloride continuous infusion at 0.25 mg/kg bw/h, after a loading dose of 0.5 mg/kg bw Concomitant medications: antacids 30 to 60 mL PRN via NG tube for persistent pH < 4, antibiotics in n = 38 Sucralfate Dose (total/d): 4 g Duration of treatment (days): 72 hours to when participant was extubated or was fed via the stomach. Study patients were enrolled an average of 4.3 days Route: NG tube Intervention: 1 g as a slurry every 6 hours via NG tube Concomitant medications: antibiotics in n = 32 Adherence to regimen: All 98 participants were admitted for a minimum of 72 hours in ICU Duration of trial: April 1991 to October 1993 Duration of follow‐up: up to 2 weeks
Outcomes	Outcomes sought in review and reported in trial Incidence of pneumonia diagnosed by criteria previously established by the Centres for Disease Control and included the following: Positive sputum gram stain and culture for specific pathogen(s) Chest radiograph demonstrating a new focal infiltrate Temperature > 38.5°C or < 36.5°C White blood cell count > 15,000 Incidence of gastric bleeding was determined on NG aspirates and classified as Occult detected by guaiac only Overt for gross blood described as 'coffee grounds', red/brown fluid, or red blood (BRB) Clinically significant ‐ requiring transfusion of blood or operative intervention Duration of intubation Duration of ICU stay All‐cause mortality in ICU Number of participants requiring blood transfusion Outcomes sought but not reported in trial report All‐cause mortality in hospital Adverse events of interventions Outcomes reported in report but not used in review Duration of hospital stay Units of blood transfused (9 for the participant from ranitidine group; the study reports only "massive transfusions" for the participant from sucralfate group)
Notes	Setting: Harborview Medical Center, 325 Ninth Avenue ZA ‐ 16, Seattle, WA 98104 Source of funding: Quote: "Supported in part by grant C#R49/CCR002570" Conflicts of interest: ‐ Ethics approval: Quote: "The study was approved by the University of Washington Human Subjects Review Board" Informed consent: Quote: "Informed consent was obtained from each patient or patient representative within 24 hours of study enrolment" Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: Of the 12 participants who were classified as having gross bleeding, 7 in ranitidine and 5 in sucralfate groups had 'coffee‐ground' aspirates
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	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. Therefore, high risk of performance bias
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: unclear on blinding of outcome assessors. However, GI bleeding was an objective outcome that was detected as per the definition in study protocol
Blinding (detection bias) Nosocomial pneumonia	Low risk	Comment: unclear on blinding of outcome assessors. However, nosocomial pneumonia was an objective outcome that was detected as per the definition in the study protocol
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: unclear on blinding of outcome assessors. However, all other outcomes of interest were objective in nature. Therefore, the likelihood of detection bias is low
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: All randomised participants completed the trial and were included in the final analysis. There are no treatment withdrawals and no trial group changes. Therefore, there is no attrition bias
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported
Other bias	Low risk	Comment: Trial is supported by a grant from the Centers for Disease and Control and Prevention CDC#R49/CCR002570. The role of the sponsor in the conduct and reporting of the trial is unclear. No other source of bias detected