Krakamp 1989.

Methods	Double‐blind randomised controlled trial
Participants	Baseline characteristics Number randomised: 30 participants Number analysed: 30 participants Overall Age (years; mean (range)): ‐ Number of participants (n): 15 in each group Gender (male/female; n): ‐ Inclusion criteria Participants in neurosurgical ICU Age > 20 years Participants selected based on expected survival owing to underlying disease after 2 days at ICU Exclusion criteria Diagnosis of upper GI bleeding Diagnosis of septicaemia Diagnosis of pneumonia Baseline imbalances: Quote: "... groups were comparable in terms of age, gender and degree of consciousness" Comment: Participants were people who were admitted to the neurosurgical ICU
Interventions	Ranitidine + placebo Dose (total/d): ‐ Duration of treatment (days): 7 Route: ‐ Intervention: ‐ Concomitant medications: ‐ Ranitidine + pirenzepine Dose (total/d): ‐ Duration of treatment (days): 7 Route: ‐ Intervention: ‐ Concomitant medications: ‐ Adherence to regimen: no dropouts. There does not seem to be any change in dosage, nor were are any adverse events mentioned Duration of trial: ‐ Duration of follow‐up: no information given. It seems that there was no further follow‐up after the end of the study
Outcomes	Outcomes sought in review and reported in trial Clinically important upper GI bleeding and related complications (haematemesis, melena, haematin in the gastric tube, haemoglobin fall > 2 g% in 48 hours) were considered as indication for endoscopy VAP (nil) All‐cause mortality in ICU Adverse events of interventions (nil) Outcomes sought but not reported in trial All‐cause mortality in hospital Duration of ICU stay Duration of intubation Number of participants requiring blood transfusion Units of blood transfused Outcomes reported but not used in review Intragastric pH
Notes	Setting: Neurosurgical ICU, Cologne, Germany Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: ‐ Informed consent : ‐ Clinical trials registration: ‐ Sample size calculation: ‐
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	Low risk	Comment: Study mentions that it is double‐blinded, but it does not describe clearly who was blinded or how this was done. However, because this is a placebo‐controlled trial, we assume that participants and study personnel were the ones blinded
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: Study mentions that it is double‐blinded, but it does not describe clearly who was blinded or how this was done. Moreover GI bleeding was an objective outcome that was detected as per the study definition
Blinding (detection bias) Nosocomial pneumonia	High risk	Comment: Study mentions that it is double‐blinded, but it does not describe clearly who was blinded or how this was done. The definition for VAP was not clearly mentioned in the study report
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: Study mentions that it is double‐blinded, but it does not describe clearly who was blinded or how this was done. Moreover outcomes were objective in nature
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: All randomised participants were part of the final analysis
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported
Other bias	Low risk	Comment: unclear on the source of funding. No additional biases were suspected