Fabian 1993.

Methods	Open‐label randomised controlled trial
Participants	Baseline characteristics Number randomised: 616 participants Number analysed: 278 participants Sucralfate Age (years; mean (range)): overall 35 (18 ‐ 78) Number of participants (n): 206 Gender (male/female; n): overall 221/66 Cimetidine bolus Age (years; mean (range)): overall 35 (18 ‐ 78) Number of participants (n): 204 Gender (male/female; n): overall 221/66 Cimetidine continuous Age (years; mean (range)): overall 35 (18 ‐ 78) Number of participants (n): 206 Gender (male/female; n): overall 221/66 Inclusion criteria Admission to trauma ICU Endotracheal intubation at the time of enrolment Nasogastric intubation at enrolment Age > 18 years Exclusion criteria History of peptic ulcer disease Receiving anti‐ulcer medications Pregnancy Baseline imbalances: After exclusion, 99 participants received sucralfate, 114 received cimetidine (bolus), and 65 received cimetidine as continuous infusion. Blunt trauma was the most common cause for admission in 72% and penetrating trauma in 28% (86% of these were gunshot wounds; 14% were stab wounds). The APACHE ll scores were 14 (5) (mean, SD) for the sucralfate group, 14 (8) (mean, SD) for the cimetidine bolus group, and 13 (6) (mean, SD) for the cimetidine infusion group
Interventions	Sucralfate Dose (total/d): 4 g Duration of treatment (days): ≥ 3 days Route: NG tube Intervention: 1 g of sucralfate suspended in 20 mL of water given via nasogastric tube or orally ever 6 hours (NG tube was clamped for 30 minutes after instillation) Concomitant medications: corticosteroids, vasopressors, and antibiotics Cimetidine bolus Dose (total/d): 900 mg Duration of treatment (days): ≥ 3 days Route: IV Intervention: 300 mg of cimetidine every 8 hours via 15‐minute IV infusions Concomitant medications: corticosteroids, vasopressors, and antibiotics Cimetidine continuous Dose (total/d): 300 mg + 960 mg Duration of treatment (days): ≥ 3 days Route: IV Intervention: 300 mg cimetidine IV as loading dose, followed by continuous infusion at an initial dose of 40 mg/h; if gastric pH < 4, it was increased by 20 mg/h to a maximum of 100 mg/h. If pH was ≥ 7, the dose was decreased by 20 mg/h to a minimum of 20 mg/h Concomitant medications: corticosteroids, vasopressors, and antibiotics Adherence to regimen: 616 participants were initially randomised to 3 treatment groups. Data on 338 participants were excluded from analysis for the following reasons: 177 participants spent less than 48 hours in the ICU (sucralfate: 52, cimetidine bolus: 52, and cimetidine continuous: 73) 28 participants were younger than 18 years of age (sucralfate: 9, cimetidine bolus: 7, and cimetidine continuous:12) 8 participants had adverse reactions (cimetidine bolus: 6 and cimetidine continuous: 2) 125 participants for protocol violations (sucralfate: 46, cimetidine bolus: 25, and cimetidine continuous: 54) The remaining 278 participants were part of the study until discharge or death Duration of trial: January 1990 to April 1991 Duration of follow‐up: Quote: "Evaluable patients were studied until discharge or death"
Outcomes	Outcomes sought in review and reported in trial Incidence of stress ulcer bleeding defined as clinically important or overt bleeding. Clinically important GI bleeding was considered present only when blood transfusion was required because of endoscopically diagnosed stress ulcers. Overt bleeding was classified as frank blood or 'coffee ground' material in nasogastric aspirate that cleared with irrigation. The presence of guaiac–positive material was not considered indicative of overt bleeding Incidence of pneumonia defined as presence of persistent infiltrate on chest roentgenography, presence of purulent tracheal aspirate, isolation of respiratory pathogen on culture, temperature > 38°C, and white blood cell count > 15 × 10³/L Note: Pneumonia developed 5.6 (1.6) (mean, SD) days after injury All‐cause mortality in ICU Duration of ICU stay Participants requiring blood transfusion Adverse reactions to Interventions Outcomes sought but not reported in trial All‐cause mortality in hospital Duration of intubation Outcomes reported in trial but not used in review Bacteral isolates from participants who developed pneumonia
Notes	Setting: Department of Surgery and Clinical Pharmacy, Presley Regional Trauma Centre, University of Tennessee, Memphis Source of funding: Quote: "Supported in part by educational grant from Smith Kline Beecham Inc" Conflicts of interest: Ethics approval: Quote: "The protocol was approved by the Institutional Review Board of The University of Tennesse, Memphis" Informed consent: ‐ Clinical trials registration: ‐ Sample size calculation: Quote: "Power analysis was made using a significance level of 0.5 a power of 0.8 and a two sided alternative hypothesis" Additional notes: In the bacterial isolates of 81 participants, Staphylococcus aureus was the most predominant followed by Haemophilus influenzae. H2 receptor antagonists were combined to form a common interventional arm vs sucralfate, as the review does not aim to investigate
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomly assigned to one of the three prophylaxis groups by random number table" 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. Moreover, the mode of administration of study drugs would not have permitted blinding
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: GI bleeding was an objective outcome that was diagnosed as per the definition in the study protocol
Blinding (detection bias) Nosocomial pneumonia	Low risk	Comment: Pneumonia was an objective outcome that was diagnosed as per the definition in the study protocol
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	High risk	Comment: Yes, around 55% of all participants who were randomised were excluded from the final analysis because of less time spent in the ICU (< 48 hours), adverse reactions, younger than 18 years of age (which was clearly an exclusion criterion), and other protocol violations. Although a per‐protocol analysis was done, there appears to be an imbalance between groups with respect to the number of participants available for analysis
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes are clearly mentioned in the study report
Other bias	Low risk	Comment: The study was supported in part by an educational grant from Smith Kline Beecham Inc. The role of the sponsor in the conduct and reporting of the trial is unclear. No other sources of bias are suspected