Driks 1987.

Methods	Parallel‐group randomised controlled trial
Participants	Baseline characteristics Number randomised: 130 participants Number analysed: 130 participants Sucralfate Age (years; mean (SD)): 53.9 (18.9) Number of participants (n): 61 Gender (male/female; n): 47/14 Antacid and/or H2 receptor antagonists Age (years; mean (SD)): 55.2 (20.1) Number of participants (n): 69 Gender (male/female; n): 42/27 Inclusion criteria Patients admitted to the surgical medical or coronary intensive care units Intubated with in the previous 24 hours receiving mechanical ventilation Nasogastric tube in place Exclusion criteria  Active upper gastrointestinal tract haemorrhage Receiving antacids, H2 blocker, or sucralfate within the previous 48 hours Duration of mechanical ventilation < 24 hours Baseline imbalances: Quote: "The two treatment groups were similar in terms of demographic characteristics and severity of illness on admission to the study" "The distribution of underlying diseases, indications for intubation and surgical procedures according to the site were similar in both the groups" "Thirty two of the 61 patients in the sucralfate group and twenty nine of the 69 participants in the antacid H2 group had infiltrates at baseline evaluation (n = 38), adult respiratory distress syndrome (n = 8), or congestive heart failure (n = 15), making it difficult to diagnose new infiltrates on a chest film" Comment: similar distribution with respect to demographic and baseline risk factors. However, a total of 35 participants (sucralfate: n = 16; antacid and/or H2: 19) had pneumonia on admission and/or had infiltrates (as mentioned above)
Interventions	Sucralfate Dose (total/d): 4 g Duration of treatment (days; mean (SE)): ‐ Route: NG tube Intervention: 1 g every 6 hours sucralfate was suspended in 20 mL of sterile water and administered by nasogastric tube, which was then flushed with 10 mL of sterile water to prevent clogging Concomitant medications: 21 participants in the sucralfate group received tube feeds; treating physician sometimes added antacids if gastric ph could not be maintained at a level ≥ 4 Antacid and/or H2 receptor antagonists Dose (total/d): 5 g Duration of treatment (days; mean (SE)): ‐ Route: NG tube Intervention: conventional therapy with antacids, H2 blockers (cimetidine or ranitidine), or both antacids and H2 blockers. Standard regimens of various antacid preparations were administered by nasogastric tube. In some patients, the dosage was titrated to maintain gastric pH ≥ 4. Similarly standard doses of intravenous cimetidine or ranitidine were prescribed. The treating physician sometimes added antacids if gastric pH could not be maintained at a level ≥ 4. In all, 39 participants received antacids alone, 17 received H2 blockers (cimetidine or ranitidine), and 13 received both H2 blockers and antacids Concomitant medications: 34 participants in the antacid‐H2 group received tube feeds; the treating physician sometimes added antacids if gastric pH could not be maintained at a level ≥ 4 Adherence to regimen: Quote: "Six patients who were initially assigned to sucralfate but subsequently assigned to antacids or H2 blockers by the treating physician were included in the sucralfate group (for analysis), no patients were switched from antacids or H2 blockers to sucralfate. Four of the six patients who were crossed over had evidence of upper GI tract bleeding, the other two who were switched to antacids 5 and 11 days after randomisation had no evidence of such bleeding. Two of the six patients had pneumonia after the crossover occurred but were included in the sucralfate group" "Four patients in the sucralfate group and 17 in the antacid‐H2 group underwent tracheostomy" Comment: ITT was performed for the review and not per‐protocol analysis Duration of trial: April 1986 to February 1987 Duration of follow‐up: until 48 hours after extubation
Outcomes	Outcomes sought in review and reported in trial Clinically important upper GI bleeding: nasogastric aspirates examined for bright red blood, 'coffee ground' material, occult blood as detected by guaiac test VAP diagnosed if chest film showed a new and persistent infiltrate that was consistent with pneumonia and ≥ 3 of the following findings: Purulent sputum that showed > 25 leucocytes on gram staining, < 10 squamous epithelial cells per low‐powered field, and numerous bacteria per oil immersion field An important respiratory or nosocomial pathogen isolated from culture of a tracheal aspirate. Peripheral leucocytosis > 10,000 cells/mm³ and fever (temperature > 38°C). Episodes of pneumonia that occurred within the first 24 hours of intubation were included; only the first episode was included for each patient Note: Pneumonia developed after 9.6 (4.6) days in sucralfate group and after 9.6 (6.3) days in antacid H2 group All‐cause mortality in ICU Duration of ICU stay Duration on ventilation Participants requiring blood transfusion Outcomes sought but not reported in trial All‐cause mortality in hospital Number of units of blood transfused Adverse events of interventions Outcomes reported in trial but not used in review Intragastric pH status Bacteriological examination
Notes	Setting: surgical, medical, or coronary intensive care units, Boston City Hospital Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: Quote: "The study protocol was reviewed and approved by the hospital institutional review board for human studies" Informed consent: ‐ Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: Quantitative data were extracted for the 2 randomised groups alone (sucralfate and antacid ‐ H2 receptor groups). Data were not extracted separately for participants treated with antacid or H2 receptor alone, as this would break the randomisation. Of bacteria isolated from the tracheal aspirates of participants treated with pneumonia, gram‐negative bacilli were predominant; Pseudomonas aeruginosa in the sucralfate group; Enterobacteriaceae in antacid‐H2 group
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: not clearly mentioned in the trial report
Allocation concealment (selection bias)	Unclear risk	Comment: not clearly mentioned in the trial report
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: This was not a placebo‐controlled trial, and the mode of administration of the interventions would not have permitted blinding of participants
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: unclear whether outcome assessors were blinded, but GI bleeding was an objective outcome that was detected as per the definition in the trial protocol
Blinding (detection bias) Nosocomial pneumonia	Low risk	Quote: "Chest roentgenograms were interpreted by at least one of us, who had no knowledge on the patient's treatment group after randomisation" Comment: Blinding was done. Moreover, pneumonia was an objective outcome that was detected as per the definition in the trial protocol
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: unclear whether outcome assessors were blinded. Moreover the outcomes of interest were objective in nature
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: Intention‐to‐treat analysis was performed wherein all participants who were initially randomised to each of the 2 study groups were part of the final analysis
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes have been reported
Other bias	Low risk	Comment: Source of funding is not clearly mentioned in the trial report. No other form of bias was detected