Bresalier 1987.

Methods	Open‐label parallel‐group trial
Participants	Baseline characteristics Number randomised: 83 participants Number analysed: 74 participants Antacids Age (years; mean (SD)): 50 (18) Number of participants (n): 36 Gender (male/female; n): 25/11 Sucralfate Age (years; mean (SD)): 54 (19) Number of participants (n): 38 Gender (male/female; n): 29/9 Inclusion criteria Admitted to surgical, medical, or burn ICU Having major trauma, burns injury, postoperative complications, or major medical illness Entering the study within 48 hours of admission to ICU Remaining in the study for at least 12 hours Having a minimum of 2 risk factors necessary to predispose patient to stress‐related mucosal injury at the time of injury, such as respiratory failure, documented respiratory insufficiency, or pneumonia requiring mechanical ventilator assistance for longer than 24 hours; hypotension/shock requiring the use of pressor agents; sepsis; burns; renal failure; hepatic failure; central nervous system injury or coma; or severe cardiac decompensation Exclusion criteria Having oesophageal, gastric, or duodenal mucosal disease; oesophageal variceal bleeding; or oesophageal or gastric surgery within past 6 months Receiving salicylates or NSAIDs, anti‐coagulants, or H2 receptor blocking agents Having GI bleeding (as demonstrated through nasogastric aspirates) Receiving oral feedings or tube feedings greater than 50 mL/h Age < 18 years Pregnancy Baseline imbalances: The 2 groups were almost similar with respect to age, gender, and time from entry into ICU to random selection. However, the sucralfate group had more risk factors for bleeding on admission to the study when compared with the antacid group (respiratory failure was the most common ‐ 34 and 37 participants, respectively). Three participants in the antacid group had coagulopathy vs 1 participant in the antacid group. Two participants in the antacid group were given a diagnosis of pneumonia on admission
Interventions	Antacids (Maalox Therapeutic Concentration) Dose (total/d): varied Duration of treatment (hours; mean (range)): 57 (14‐297) Duration of follow‐up (days; mean (SD)): 21 (20) Route: ‐ Intervention: 30 mL every 2 hours for maintaining gastric pH ≥ 4. If gastric pH was < 4, dosage was increased to 30 mL every hour, 60 mL every 2 hours, or 60 mL/h as needed to maintain pH ≥ 4 Concomitant medications: ‐ Sucralfate Dose (total/d): 6 g Duration of treatment (hours, mean (range)): 60 (12‐360) Duration of follow‐up (days; mean (SD)): 20 (13) Route: NG tube Intervention: 1 g (10 mL) every 4 hours per nasogastric tube Concomitant medications: ‐ Adherence to regimen: Six participants from the antacid group (n = 42) and 3 from the sucralfate group (n = 41) were excluded from analysis for the following reasons: < 12 hours in the study (3 died, 2 enteral feeds, 1 severe diarrhoea, with treatment discontinued), received both interventions, had evidence of GI bleed before intervention, refused participation Duration of trial: January 1984 to September 1985
Outcomes	Outcomes sought in review and reported in trial Incidence of clinically relevant upper GI bleeding defined as Bright red blood in the nasogastric tube that was not cleared by a 2‐liter saline lavage Decrease in haematocrit by more than 3 percentage points in 24 hours, accompanied by Stool that yielded positive results when tested for occult blood with Haemoccult and no evidence of lower gastrointestinal bleed, or a decrease in haematocrit level of more than 6 percentage points in 48 hours with no evidence of extra gastrointestinal source or no evidence of lower gastrointestinal bleeding All‐cause mortality in ICU Number of participants requiring blood transfusion Adverse events of interventions Outcomes sought but not reported in trial VAP All‐cause mortality in hospital Duration of ICU stay Duration of intubation Outcomes reported in trial but not used in review Relationship between underlying risk factors and development of upper GI bleeding Gastric pH values Medicine doses missed
Notes	Setting: surgical, medical, or burn intensive care units at San Francisco General Hospital, USA Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: Quote: "The protocol was approved by the University of California, San Fransisco, Hum and Environmental protection committees (approval number 251701‐02)" Informed consent: "obtained from all participants. If the participant was unable to provide informed consent, then the participant's next of kin or legally authorized representative provided consent. If they could not be contacted, then the participant's attending physician was asked to provide permission" Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: One participant in each group had significant upper GI bleeding after the trial was completed
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information on sequence generation reported
Allocation concealment (selection bias)	Unclear risk	Comment: no information on allocation concealment reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: Participants and personnel involved in the trial were not blinded
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: GI bleeding was an objective outcome that was diagnosed as per the definition used in the trial protocol
Blinding (detection bias) Nosocomial pneumonia	Unclear risk	Comment: Trial did not address this outcome
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Unclear risk	Comment: unclear whether outcome assessors were blinded. Moreover, criteria for diagnosis of other outcomes of interest not clearly reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: Not all randomised participants were included in the final analysis (83 were randomised, 74 were included in the analysis). A per‐protocol analysis was done, as 9 participants were involved in the trial for less than 12 hours. There was no imbalance between groups. Therefore, low risk of bias is due to attrition
Selective reporting (reporting bias)	Unclear risk	Comment: not enough information reported on outcomes of relevance in the trial
Other bias	High risk	Comment: Source of funding is not clearly mentioned in the trial report. No other sources of bias are suspected, but insufficient information is reported in the trial abstract