Kappstein 1991.

Methods	Parallel‐group quasi‐randomised controlled trial
Participants	Baseline characteristics Number randomised: 104 participants Number analysed: 104 participants Sucralfate Age (years; mean (SD)): 40.6 (21.1) Number of participants at baseline (n): 49 Gender (male/female; n): 38/11 Cimetidine Age (years; mean (SD)): 46.2 (21.0) Number of participants at baseline (n): 55 Gender (male/female; n): 46/9 Inclusion criteria Admitted to the anesthesiology intensive care unit Requiring mechanical ventilation for at least 24 hours Having a nasogastric tube in place Exclusion criteria Upper abdominal or thoracic surgical interventions Being tube‐fed Baseline imbalances: The 2 groups were largely similar according to demographic characteristics, underlying diseases, and diagnoses at admission. However, there were slight imbalances with regard to age, gender, polytrauma, and acute respiratory failure
Interventions	Sucralfate Dose (total/d): 4 g Duration of treatment (days): ‐ Route: nasogastric tube Intervention: 1 g sucralfate every 6 hours through the nasogastric tube, which was subsequently rinsed with 10 mL of sterile water to avoid residues of the suspension in the tube lumen. Tubes were then clamped for about 1 hour to prevent reflux Concomitant medications: ‐ Cimetidine Dose (total/d): 2000 mg or 1200 mg Duration of treatment (days): ‐ Route: IV Intervention: not pH adjusted. There was no difference in mean gastric pH levels of patients receiving cimetidine continuously (2000 mg/d) or intermittently (3 × 400 mg/d) Concomitant medications: ‐ Adherence to treatment: ‐ Duration of trial: May 1986 to January 1989 Duration of follow‐up (days): ‐
Outcomes	Outcomes sought in review and reported in trial GI bleeding: Macroscopically visible blood in gastric aspirates was taken for evidence of stress bleeding Ventilator‐associated pneumonia: Diagnosis of pneumonia was established if there was a new and persistent infiltrate on chest X‐ray and at least 3 of the following signs consistent with infection: (a) purulent tracheal secretions (> 25 polymorphonuclear leucocytes and < 10 squamous epithelial cells per low‐ power field); (b) a pathogen known to cause lung infection isolated from tracheal secretions; and (c) blood leucocytosis > 10,000 cells/mm³ and fever with body temperature > 38°C. Shock was defined by systolic blood pressure < 90 mmHg. Sepsis was diagnosed if there was bacteriologically confirmed or clinical sepsis Mortality Duration of ventilation Outcomes sought in review, but not reported in trial Duration of ICU stay Blood transfusion Adverse events of interventions Outcomes reported in trial but not sought in review Gastric colonisation Gastric pH levels
Notes	Setting: ICU, Department of Hospital Epidemiology, Medical Biometry and Anaesthesiology, University Hospital Freiburg, Germany Sponsorship source: ‐ Conflicts of interest: ‐ Ethics approval: ‐ Informed consent: ‐ Clinical trials registration: ‐ Sample size calculation: ‐ Comment: ‐
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "and tube‐fed patients were excluded. Patients were assigned to stress ulcer prophylaxis with either sucralfate or cimetidine by setting up groups of 10 patients who received one prophylactic regimen followed by the next 10 patients receiving the other regimen. Patients received either intravenous" Judgement comment: quasi‐randomisation. Patients were assigned to stress ulcer prophylaxis with either sucralfate or cimetidine by setting up groups of 10 patients who received 1 prophylactic regimen followed by the next 10 patients receiving the other regimen
Allocation concealment (selection bias)	Unclear risk	Judgement comment: Provided the sequence was consecutive, patients were known in each group
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Judgement comment: no blinding reported, but lack of blinding is unlikely to introduce bias. Outcome measures and outcomes are objectively measured
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Quote: "Macroscopically visible blood in gastric aspirates was taken for evidence of stress bleeding" Comment: outcome measured objectively
Blinding (detection bias) Nosocomial pneumonia	Low risk	Comment: criteria for the diagnosis of pneumonia clearly reported in the trial
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	High risk	Quote: "The chest x‐ray was interpreted by a radiologist who was not aware of the particular prophylactic regimen" Judgement comment: but investigators and personnel were unblinded for other criteria for pneumonia and for other outcomes
Incomplete outcome data (attrition bias) All outcomes	Low risk	Judgement comment: All outcomes have included all patients. No incomplete reporting of data suspected. Attrition was low and was reported transparently
Selective reporting (reporting bias)	Low risk	Judgement comment: no incomplete reporting of outcomes suspected. All outcomes listed in the Methods section are also reported in the Results section
Other bias	Low risk	Comment: no other sources of bias suspected