Kitler 1990.

Methods	Randomised controlled trial
Participants	Baseline characteristics Number randomised: 401 participants Number analysed: 298 participants Overall Age (years; mean (range)): ‐ (19 to 65) Number of participants (n): 298, n = 85 bioflavonoid (Maciadanol), n = 100 sucralfate, n = 113 antacids Gender (male/female; n): 197/101 Inclusion criteria Patients admitted to surgical ICU of Johns Hopkins and Francis Scott Key Medical Centres in Baltimore Patients who consented to enter the study Exclusion criteria Patient refusal to enter the study or surgeon refusal to allow the patient entry Patients with active bleeding of the GI tract Recent acute symptoms of peptic ulcers Recent operations of the stomach or oesophagus Known renal failure Baseline imbalances: Most participants were referred for cardiac surgical treatment. Groups were similar in demographic characteristics such as age and race. The sucralfate group had the fewest women. Ten participants assigned to receive meciadanol had a history of peptic ulcer disease (3 with a history of bleeding); 14 with sucralfate had a history of peptic ulcer disease (5 with a history of bleeding), and 13 assigned to receive antacid had a history of peptic ulcer disease (4 with bleeding)
Interventions	Bioflavonoid (Maciadanol) Dose (total/d): 3000 mg Duration of treatment (days): ‐ Route: NG tube Intervention: 500 mg ever 6 hours through NG tube. Maciadanol was dissolved in sterile normal saline (10 mL) immediately before administration Concomitant medications: aspirin, steroids, indomethacin, sodium warfarin, and heparin Sucralfate Dose (total/d): 5000 mg Duration of treatment (days): ‐ Route: NG tube Intervention: 1000 mg (1g) in sterile normal saline solution through NG tube every 6 hours. Tablets were crushed immediately before administration and the resulting powder was suspended in sterile normal solution Concomitant medications: aspirin, steroids, indomethacin, sodium warfarin and heparin Antacids (Maalox, magnesium aluminium hydroxide gel) Dose (total/d): 360 mL Duration of treatment (days): ‐ Route: ‐ Intervention: dosage mentioned as an initial dose of 15 mL every hour (in abstract) “in a manner similar to the protocol reported by others” Concomitant medications: aspirin, steroids, indomethacin, sodium warfarin, and heparin Adherence to regimen: Overall 401 patients had entered the study and 298 had completed the study. Those who did not complete the study could not be evaluated or were excluded because of protocol error (receiving other antacids or antiulcer drugs), by physician request, or by their own request. Participants who remained in SICU for less than 24 hours were also excluded from the study. 85 participants completed the maciadanol arm, 100 the sucralfate arm, and 113 the antacid arm Duration of trial: 16 months Duration of follow‐up: ‐
Outcomes	Outcomes sought in review and reported in trial Clinically important upper GI bleeding (frank bleed) determined visually (frank blood in gastric contents) or by guaiac testing All‐cause mortality in ICU (not reported for each arm) Duration of ICU stay (mean and SD not reported) Participants requiring blood transfusions Outcomes sought but not reported in trial VAP All‐cause mortality in hospital Units of blood transfused Duration of intubation Adverse events of interventions Outcomes reported in trial but not used in review Intragastric pH
Notes	Setting: Surgical Intensive Care Unit of Johns Hopkins Medical Institutions, Baltimore, and Francis Scott Key Medical Centre, Baltimore Source of funding: Zyma, S. A., Nyon, Switzerland Conflicts of interest: Ethics approval: Quote: "The study was approved by the institutional review board of Johns Hopkins Medical Center and the Francis Scott Key Medical Center" Informed consent: mentioned in the study report Clinical trials registration: ‐ Sample size calculation: Quote: "The power calculations resulting from study sample size were one tailed with an alpha of 0.05 and a power of 80.0 per cent..."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomised by a table of random numbers..." Comment: Method adopted to obtain random sequence generation is clearly mentioned in the study report
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, and the different modes of administering the study interventions would not have made it possible to blind study personnel and participants
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Quote: "All data were collected by an observer unaware of the results" Comment: not clear how this would have contributed to blinding. GI bleeding was detected as per the definition in the study. However, owing to the objective nature of the outcome of interest, the likelihood of performance and detection bias is low
Blinding (detection bias) Nosocomial pneumonia	Unclear risk	Comment: Study did not address this outcome
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Quote: "All data were collected by an observer unaware of the results" Comment: unclear on blinding of outcome assessors. However, all other outcome data were objective in nature
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: Overall 401 patients had entered the study and 298 had completed the study. Study did a per‐protocol analysis for outcomes. Participants in the Maciadanol arm were 24% less than in the antacid arm. Unclear whether this could have influenced outcomes
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported in the study report
Other bias	Low risk	Comment: Source of funding is mentioned. The role of the sponsor in the conduct and reporting of the trial is unclear. No other sources of bias are suspected