Laggner 1989.

Methods	Single‐blind randomised controlled trial
Participants	Baseline characteristics Number randomised: 32 participants Number analysed: 32 participants Sucralfate Age (years; mean (SD)): 47 (19) Number of participants (n): 16 Gender (male/female; n): 11/5 Ranitidine Age (years; mean (SD)): 60 (15) Number of participants (n): 16 Gender (male/female; n): 7/9 Inclusion criteria  Participants with acute onset of respiratory illness that required mechanical ventilation of more than 48 hours. Exclusion criteria Age < 18 and > 80 years Bleeding from nasopharynx, upper gastrointestinal tract Requiring mechanical ventilation of < 49 hours, or > 12 hours before the study commenced Known allergy to sucralfate and ranitidine Baseline imbalances: Quote: "Male: female ratios and mean age of the two treatment groups appear not quite similar,but we could not detect any significant difference" Comment: All participants were long‐term ventilated persons
Interventions	Sucralfate Dose (total/d): ‐ Duration of treatment (days, mean (SD)): 11.8 (7.9) Route: NG tube Intervention: sucralfate gastric tube every 4 hours. After administration of sucralfate, tubes were clamped for 60 minutes Concomitant medications: All participants were receiving total parenteral nutrition. All participants received mechanical ventilation with volume‐cycled ventilators and had soft nasogastric tubes. Antibiotics Ranitidine Dose (total/d): 300 mg Duration of treatment (days, mean (SD)): 10.1 (3.6) Route: IV Intervention: intravenously as bolus injections of 50 mg every 4 hours. If gastric pH was < 3.5, ranitidine dosage was increased to 100 mg Concomitant medications: All participants were receiving total parenteral nutrition. All participants received mechanical ventilation with volume‐cycled ventilators and had soft nasogastric tubes. Antibiotics Adherence to regimen: ‐ Duration of trial: ‐ Note duration of treatment: Quote: "The study was terminated when the patient was dismissed from the intensive care unit or died" Duration of follow‐up: not clearly mentioned in the study report
Outcomes	Outcomes sought in review and reported in trial Clinically important upper GI bleeding diagnosed in participants with gastric aspirates and/or haematemesis VAP diagnosed by appearance of an infiltrate on the chest radiograph with concomitant bronchial colonization, leucocytosis > 15,000/mm³, and fever higher than 38.5°C All‐cause mortality in ICU Participants requiring blood transfusion Duration of ICU stay Outcomes sought but not reported in trial All‐cause mortality in hospital Duration of intubation Units of blood transfused Adverse events of interventions Outcomes reported in trial but not used in review Gastric pH Bacterial colonisation of bronchial secretions
Notes	Setting: Department of Medicine, University of Vienna, Austria Source of funding: ‐ Conflicts of interest: Ethics approval: Quote: "The study was approved by the local ethical committee" Informed consent: Quote: "...and informed consent was obtained from the next of kin after the potential complications of the procedures were explained" Comment: Consent was obtained Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: Quote: "During mechanical ventilation, upper gastrointestinal bleeding developed in three sucralfate‐ and seven ranitidine‐treated patients (18.7 versus 43.7 percent, p < 0.05). Until the end of the study, bleeding developed in only three sucralfate‐ but nine ranitidine treated patients (18.7 versus 56.2 percent, p ˜ 0.05)" Comment: Data for 9 participants (in ranitidine) were taken for analysis because it was felt that this occurred when participants were still in the ICU. One death in each group was attributed to GI bleed
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: ":.. 32 mechanically ventilated patients were randomly assigned, according to a preset table, to receive either ranitidine or sucralfate" Comment: not clear on how the sequence was generated in the "preset table"
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 different modes of administering study drug would not have made it possible to blind participants. Therefore the likelihood of performance bias is high
Blinding (detection bias) Clinically important upper GI bleeding	High risk	Comment: unclear whether outcome assessors were blinded to this outcome. The definition of this outcome was not clearly described in the study report
Blinding (detection bias) Nosocomial pneumonia	Low risk	Quote: ”Analysis of chest radiographs was performed by a radiologist, who was not aware of the radiologist, who was not aware of the clinical status or the therapy of the patients” Comment: Outcome assessors for nosocomial pneumonia were blinded
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: unclear whether outcome assessors were blinded to other outcomes of interest. However, outcomes were objective in nature. Therefore the likelihood of performance and detection bias is low
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 reported in the study
Other bias	Low risk	Comment: unclear on the source of funding. No other sources of bias suspected