Kantorova 2004.

Methods	Single‐center randomised placebo‐controlled trial
Participants	Baseline characteristics Number randomised: 323 participants Number analysed: 287 participants Omeprazole Age (years; mean (range)): 44 +/‐15 Number of participants (n): 72 Gender (male/female; n): 48/24 Famotidine Age (years; mean (range)): 47+/‐17 Number of participants (n): 71 Gender (male/female; n): 44/27 Sucralfate Age (years; mean (range)): 51 +/‐ 18 Number of participants (n): 69 Gender (male/female; n): 50/19 Placebo Age (years; mean (range)): 18,46 +/‐19. Number of participants (n): 75 Gender (male/female; n): 50/25 Inclusion criteria Age ≥ 18 years Projected to require mechanical ventilation for at least 48 hours  Having coagulopathy Having a nasogastric tube in place Exclusion criteria Expected stay in ICU ≤ 48 hours History of oesophagogastric surgery including vagotomy Evidence of GI bleeding at the time of admission to the ICU and during the previous year Pneumonia Treatment with PPIs, H2 blockers, antacids, or sucralfate during previous 72 hours Documented peptic ulcer disease during the year Use of systemic anticoagulants, high‐dose oral corticosteroids, or thrombolytic agents during previous week Renal insufficiency requiring haemodialysis Thrombocytopaenia < 30,000/mL Participants with life expectancy < 3 months Participants not able or willing to give informed consent Baseline imbalances: Quote: "At randomisation no statistically significant difference was found among the four groups in demographic and baseline physiological characters. The distribution of risk factors such as participants who had trauma, surgery or coagulopathy at ICU admission were also similar in all groups" Comment: no significant difference between the 2 groups with respect to demographic and baseline risk factors. Trauma was the main reason for admission. Coagulopaty was diagnosed in 31 participants at baseline (7, 10, 6, and 8 in each of the 4 groups, respectively)
Interventions	Omeprazole Dose (total/d): 40 mg Duration of treatment (days): ‐ Route: IV Intervention: 40 mg of omeprazole intravenously once daily Concomitant medications: Enteral feeding was administered to 30 participants, antibiotic therapy to 65 participants Famotidine Dose (total/d): 80 mg Duration of treatment (days): ‐ Route: IV Intervention: 40 mg twice a day at 12‐hour intervals by slow intravenous injection Concomitant medications: Enteral feeding was administered to 25 participants, antibiotic therapy to 62 participants Sucralfate Dose (total/d): ‐ Duration of treatment (days): ‐ Route: ‐ Intervention: administered every 6 hours as 1 g of suspension Concomitant medications: Enteral feeding was administered to 29 participants, antibiotic therapy to 66 participants Placebo Dose (total/d): ‐ Duration of treatment (days): 3.1 Route: IV Intervention: not clearly reported. Probably 100 mL in saline solution IV (like group 1 and group 2 interventions) Concomitant medications: Enteral feeding was administered to 26 participants, antibiotic therapy to 71 participants Notes for placebo intervention: A placebo group was included in the protocol design because at study initiation and during the study period, no drug was approved for prophylaxis of stress‐related upper gastrointestinal bleeding by the FDA. The European Medicines Evaluation Agency required a placebo comparison group for registration of studies in this indication Adherence to regimen: Quote: "Of the 323 randomised patients 36 were subsequently excluded from analysis (1 patient died suddenly within 2 hours after randomisation, 18 underwent mechanical ventilation < 48 hours and 16 were not assessable because of missing important data" Thus only 287 patients could be analysed. No drug‐related adverse events were seen during the whole study, possibly related adverse events were rare, and in no patient was discontinuation of therapy necessary. Duration of trial: February 2000 to June 2002 Duration of follow‐up: ‐
Outcomes	Outcomes sought in review and reported in trial Clinically important upper GI bleeding (haematemesis, melena, positive nasogastric aspirate, or haematochezia) defined as overt bleeding plus at least 1 of the following: Drop in systolic blood pressure within 24 hours after upper GI bleeding of 20 mmHg or increase in pulse rate ≥ 20 beats per minute with more than 24 hours of upper GI bleeding Drop in haemoglobin concentration ≥ 2 g/dL in the absence of a clear explained reason VAP Purulant tracheal aspirate with more than 25 leucocytes per low‐power field Episodes of pneumonia diagnosed within first 24 hours of admission were considered to be present on admission Peripheral leucocytes > 11 × 10⁹/L or > 10% bands Central body temperature > 38.4°C Isolation of pathogens from tracheal aspirate, bronchoalveolar lavage Positive haemo culture or pleural fluid culture unrelated to another source Secondary outcomes All‐cause mortality in ICU All‐cause mortality in hospital Duration of ICU stay Duration of intubation Participants requiring blood transfusion (could not be analysed owing to low incidence of bleeding) Units of blood transfused (could not be due to low incidence of bleeding) Adverse events of interventions (no adverse events reported) Outcomes sought but not reported in trial report Nil Outcomes reported in trial but not used in review Intragastric pH status Gastric colonisation
Notes	Setting: Traumatological Hospital Brno, a Czech republic ministry of health teaching and research facility Source of funding: Quote: "The study was supported by a grant of IGA MZ CB ND 5932‐3/2000" Conflicts of interest: Ethics approval: Quote: "The study was approved by the Institutional Review Board and Grant agency at the Misnistry of Healthof Chez Republic" Informed consent: Quote: "participants not able or willing to give informed consent were eluded from the study" Clinical trials registration: not provided in the study report Sample size calculation: not mentioned in the study report Additional notes: GI bleeding occurred more commonly in participants with coagulopathies (3/31, 10% vs 4/245, 2%, P = 0.006). The most common pathogens in participants with pneumonia were Staphylococcus andStreptococcus. ICU stay and mortality were greater in participants with investigated complications of GI bleed and pneumonia but were not influenced by prophylaxis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomly assigned to study group by means of computer generated random number table to generate a random treatment list" Comment: method adopted to obtain random sequence generation clearly mentioned in the study report
Allocation concealment (selection bias)	Low risk	Quote: "Treatment regimens were included in opaque sealed numbered envelopes and the envelope with the lowest number was always used for the consecutive patient" Comment: method adopted to allocation concealment clearly mentioned in the study report
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "Blinding of the drug administered intravenously was achieved by dissolving them in 100 mL of saline solution drug were prepared by staff not involved in the study according to the randomisation. All blinded drugs were identifiable by their study number and were given to the patients by the study nurse" Comment: Blinding is mentioned only for groups that received intravenous medications (omeprazole, famotidine, and placebo), not sucralfate. Unclear whether this would have led to performance bias
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: mentioned that outcome assessment was done blinded to intervention. The presence of 1 or more macroscopic abnormalities (erythema or oedema, erosions, ulcerations, and naso‐gastric tube lesions) and GI bleeding was assessed, blinded to intervention, at endoscopy by a single experienced gastroenterologist Quote: "assessed, blinded to intervention, at endoscopy by a single experienced gastroenterologist"
Blinding (detection bias) Nosocomial pneumonia	Low risk	Quote: "Chest radiographs were interpreted by two independent radiologists" Comment: Blinding of outcome assessors was done. Pneumonia was an objective outcome detected as per the study protocol
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: All other outcomes of interest were objective in nature, so the likelihood of detection bias is low
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: Of the 323 randomised patients, 36 were subsequently excluded from analysis. Groups to which they were initially randomised remain unclear though. Thus only 287 participants were available for analysis. However, the number of dropouts and their characteristics were comparable in all 4 arms. Therefore there is no likelihood of risk of attrition bias
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported in the study
Other bias	Low risk	Comment: Study was funded by a grant of IGA MZ CB ND 5932‐3/2000. The role of the sponsor in the conduct and reporting of the trial is unclear. No other sources of bias were detected