Eddleston 1994.

Methods	Parallel‐group randomised controlled trial
Participants	Baseline characteristics Number randomised: 26 participants Number analysed: 26 participants Sucralfate Age (years; mean (SD)): 47.6 (5.4) Number of participants (n): 14 Gender (male/female; n): 9/5 Placebo Age (years; mean (SD)): 54.9 (5.7) Number of participants (n): 12 Gender (male/female; n): 8/4 Inclusion criteria Expected to require mechanical ventilator support for ≥ 4 days Participants diagnosed with risk factors to develop stress ulceration Sepsis Hypotension (mean arterial pressure < 65 mm) Respiratory failure Renal dysfunction Hepatic dysfunction Exclusion criteria Participants who had the following conditions: Previous history of peptic ulcer disease Gastric surgery Fresh blood in nasogastric aspirate Clinical evidence of pulmonary aspiration Pneumonia CNS injury or coma Pregnancy Treatment within previous 4 weeks with histamine receptor antagonists, antacid, omeprazole, or NSAIDs Baseline imbalances: Participants in the placebo group were relatively older. Acute Pysiology and Chronic Health Evaluation II (APCHEII) scores were 12.5 (1.7) and 14.7 (2.2), respectively. Trauma was the most common cause for admission (6 in sucralfate group and 4 in the placebo group)
Interventions	Sucralfate Dose (total/d): 6 g Duration of treatment (days; mean (SD)): ‐ Route: NG tube Intervention: 2 g/10 mL every 8 hours via NG tube flushed with10 mL of sterile water Concomitant medications: Prophylactic antibiotics were administered to 11 participants from both groups Placebo Dose (total/d): ‐ Duration of treatment (days; mean (SD)): ‐ Route: NG tube Intervention: 20 mL of sterile water every 8 hours via NG tube Concomitant medications: Prophylactic antibiotics were administered to 11 participants from both groups Adherence to regimen: Treatment began within 8 hours of ICU admission. Endoscopy performed on day 3 in the placebo group revealed acute ulcerations in 5 participants, as a result of which they were withdrawn and put on sucralfate 2 g every 8 hours. On day 6, 2 more patients from placebo group were switched over to sucralfate owing to acute gastric ulceration. Mucosal deterioration and acute ulceration were significant in the placebo group. The study was halted after recruitment of 26 participants for ethical reasons Duration of trial: ‐ Duration of follow‐up: ‐
Outcomes	Outcomes sought in review and reported in trial Incidence of pneumonia, defined as per the criteria of a new and progressive infiltrate on chest radiograph, an unexplained reduction in PaP2; positive culture with a tracheal aspirate with pyrexia (> 38°C) or an increase in blood leucocyte count(> 3 × 10⁹ WBCs/L). Furthermore the same organism had to be colonised in ascending order: stomach, oropharynx, and trachea Clinically important GI bleeding reported as fresh blood in the nasogastric tube All‐cause mortality in ICU Note: GI bleeding occurred in 1 participant from placebo group on 20th day of the trial Outcomes sought but not reported in trial All‐cause mortality in hospital Participants requiring blood transfusions Adverse events of interventions Outcomes reported in trial but not used in review Intragastric pH status (with and without enteral nutrition) Inflammation, erosion, and ulceration of gastric and duodenal mucosa through endoscopy within 24 hours; third, sixth, and tenth days if patient still on mechanical ventilator and cardiovascularly stable Gastric colonisation Duration of endotracheal intubation (subgrouped for participants with and without erosions and ulcerations) Length of stay in ICU (subgrouped for participants with and without erosions and ulcerations)
Notes	Setting: Department of Surgery, Critical Care Unit, Department of Microbiology, Manchester Royal Infirmary, Manchester, UK Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: Quote: "The protocol for the study was approved by the hospital ethics committee" Informed consent: Quote: "...informed consent was obtained from the patient's next of kin" Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: Oropharyngeal retrograde colonisation occurred in 1 participant in the sucralfate group and in 2 participants in the placebo group. Tracheal colonisation occurred in 2 participants from the sucralfate group and in 1 participant from the placebo group. However only the latter developed pneumonia. Mortality in ICU was attributed to multiple organ failure
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were allocated by the use of a random sampling table into two groups..." Comment: Method adopted to obtain random sequence generation is 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	Unclear risk	Comment: This was a placebo‐controlled trial, and the mode of administering the interventions was similar. However, unclear whether personnel and participants were blinded
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Quote: "Endoscopic evolution of the gastric and the duodenal mucosa was performed within 24 hours of admission by an operator who was blinded to the randomisation code and was repeated on day 3, 6 and 10 if the participant was still receiving mechanical ventilation" Comment: Interim gastroscopy was performed if there was fresh blood in the nasogastric aspirate, but the endoscopist was blinded. However, the outcome of interest was objective in nature
Blinding (detection bias) Nosocomial pneumonia	Low risk	Comment: no mention of blinding of radiologists, lab technicians, or physicians. However, pneumonia was diagnosed as per the study definition and due to the objective nature of the outcome
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: no clear mention of blinding of outcome assessors. However owing to the objective nature of the outcomes, the likelihood of detection bias is low
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: All participants randomised were included in the analysis
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes are reported, although unclear on adverse events
Other bias	Low risk	Comment: Source of funding is not clearly mentioned in the trial report. No other sources of bias are suspected