Laggner 1988.

Methods	Open‐label randomised controlled trial
Participants	Baseline characteristics Number randomised: 84 participants Number analysed: 84 participants Ranitidine Age (years; mean (SD)): 57.3 (18.8) Number of participants (n): 43 Gender (male/female; n): 25/18 Sucralfate Age (years; mean (SD)): 51.1 (17.7) Number of participants (n): 41 Gender (male/female; n): 23/18 Inclusion criteria  Admitted to the ICU unit with expected duration > 3 days' stay High risk for upper GI bleeding History of ulcus Creatinine clearance < 10 mL/min/1.73 m² Respiratory support Thrombocytes < 50,000/mm³ Heparin therapy Extracorporeal therapy, e.g. haemodialysis, haemofiltration Notes: not clear whether any at all, 1, or more of these risk factors is required to be classified as high risk Exclusion criteria  Acute upper GI bleeding Baseline imbalance: Both groups were comparable with respect to age, underlying disorders, and factors predisposing to development of stress ulcers
Interventions	Ranitidine Dose (total/d): 300 mg Duration of treatment (days, mean (SD)): 8.6 (4.6) Route: IV Intervention: 6 × 50 mg/d IV as bolus injection; doubling of dose if stomach pH < 3.5 Concomitant medications: had a Nasogastric tube in place. Anticoagulants were administered to 15 participants Sucralfate Dose (total/d): 6 g Duration of treatment (days, mean (SD)): 8.9 (6.1) Route: NG tube Intervention: 6 × 1 g/d via gastric tube Concomitant medications: had a Nasogastric tube in place. Anticoagulants were administered to 15 participants Adherence to regimen: no dropouts mentioned; however, after bleeding was detected, 1 participant in the sucralfate group was switched over to ranitidine. 2 individuals in the ranitidine group who had bleeding were switched to the sucralfate group, 1 to pirenzepine; in 3, enteral feeding was started Duration of trial: 18 months Duration of treatment: until participant was discharged from ICU or when acute problem improved, so that bleeding prophylaxis was no longer deemed necessary Duration of follow‐up: until patient was discharged from ICU or prophylaxis was no longer required (unclear how this was determined)
Outcomes	Outcomes sought in review and reported in trial Incidence of stress ulcer bleeding defined as presence of macroscopically visible blood in gastric aspirates and/or haematemesis. All‐cause mortality in ICU Duration of intubation (all participants were not intubated) Outcomes sought but not reported in trial VAP All‐cause mortality in hospital Duration of ICU stay Number of participants requiring blood transfusion Units of blood transfused Adverse events Outcomes reported but not used in review Adverse reactions of interventions (no clear numbers provided) Gastric pH values Bacteriological test (blood culture, bronchial aspirate in ventilated patients) Thrombocyte counts Liver function tests Body temperature
Notes	Setting: ICU Medical University Hospital, Wien, Austria Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: ‐ Informed consent: ‐ Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: Positive bacterial cultures were obtained from bronchial secretions of (43.3% of 74 bronchial secretions in participants receiving ranitidine and 18.6% of 59 bronchial secretions in those receiving sucralfate). Only 30 participants in the ranitidine group and 25 participants in the sucralfate group needed mechanical ventilation. The duration of this was 8.6 ± 4.6 in the ranitidine group and 8.9 ± 6.1 in the sucralfate group
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: GI bleeding was detected as per the definition in the study protocol, and the the nature of the outcome of interest is objective
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: All other outcomes of interest were objective in nature, so the likelihood of performance 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. No treatment withdrawals and no trial group changes
Selective reporting (reporting bias)	High risk	Quote: "There was no difference in side effects between the two medication groups" Comment: Adverse reactions due to the interventions are not clearly mentioned in the study report. This would have caused reporting bias in the study report. All other intended outcomes are reported
Other bias	Low risk	Comment: no mention of the source of funding. No additional biases were detected