Terzi 2009.

Methods	Open‐label randomised controlled trial
Participants	Baseline characteristics Number randomised: 24 participants Number analysed: 20 participants Ranitidine Age (years; mean (SD)): 44 (20) Number of participants (n): 10 Gender (male/female; n): 5/5 Pantoprazole Age (years; mean (SD)): 45 (15) Number of participants (n): 10 Gender (male/female; n): 7/3 Inclusion criteria Written consent from a first‐degree relative of each patient Mechanically ventilated for more than 48 hours Sepsis as defined by evidence of infection and exhibited 2 or more of the criteria defined by the ACCP/SCCM Consensus Conference Exclusion criteria Age < 18 years Pregnancy or breast‐feeding Admitted to the ICU after oesophageal, gastric, or duodenal surgery History of gastrectomy or known upper GI lesion Potential for haemorrhage History or existence of a hypersecretory condition such as Zollinger‐ Ellison syndrome History or existence of peptic ulcer disease within 1 year before the study commencing Coagulation disorders Baseline imbalances: Participants were comparable with respect to age, gender, and other clinical characteristics including the presence of H pylori, APACHE II score was 12 +/‐ 7 and 16 +/‐ 4 for ranitidine and pantoprazole groups
Interventions	Ranitidine Dose (total/d): 150 mg Duration of treatment (days): ‐ Route: IV Intervention: 50 mg of the drug every 8 hours, diluted in 20 mL of 0.9% saline solution and administered by slow intravenous infusion (2 to 3 minutes) Concomitant medications: conventional treatment of sepsis, including antibiotic therapy, fluid replacement, glucose control, treatment with vasoactive drugs, and dialysis when required, in addition to routine supplementary tests. Patients remained fasting Pantoprazole Dose (total/d): 80 mg Duration of treatment (days): ‐ Route: IV Intervention: 40 mg of drug diluted in 10 mL of 0.9% saline solution and administered intravenously (2 minutes), every 12 hours at standardised times Concomitant medications: conventional treatment of sepsis, including antibiotic therapy, fluid replacement, glucose control, treatment with vasoactive drugs, and dialysis when required, in addition to routine supplementary tests. Patients remained fasting Adherence to regimen: Quote: "Four patients, 3 from ranitidine group, were excluded for technical reasons” Duration of trial: ‐ Duration of treatment: ‐ Duration of follow‐up: not clearly mentioned in the trial report. Probably until discharge or an untimely event of death
Outcomes	Outcomes sought in review and reported in trial (none of these were the primary outcomes of the trial) GI bleeding defined as a decrease in haemoglobin levels greater than 2 g/dL, a decrease in systolic arterial pressure greater than 20 mmHg, the need for a transfusion of 2 or more units of concentrated red blood cells, all within a period of 2 hours, gastric bleeding requiring surgery (No gastric bleeding was detected) All‐cause mortality in ICU Outcomes sought but not reported in trial Incidence of ventilator‐associated pneumonia All‐cause mortality in hospital Duration of ICU stay Duration of intubation Participants requiring blood transfusions Units of blood transfused Adverese reactions of interventions Outcomes reported but not used in review Gastric pH levels Investigation for H pylori
Notes	Setting: State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil Source of funding: Quote: “Support funds for research and development were provided by FAEPEX. Fundação de Apoio ao Ensino, à Pesquisa e à Extensão” Conflicts of interest: ‐ Ethics approval: Quote: "The present study was approved by the ethics committee of the State University of Campinas, Brazil (no. 035/2003, dated February 18, 2003)" Informed consent: Quote: "The informed consent form was signed by a relative of each patient included in the study, as required by Resolution no. 196/96 of the National Health Council, Brazilian Ministry of Health, concerning research involving human beings" Clinical trials registration: ‐ Sample size calculation: ‐
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: not 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 different modes of administering the study interventions would not have made it possible to blind study personnel and participants.Therefore, high risk of performance bias
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: This was an open‐label trial, and outcome assessors were not blinded. However GI bleeding was an objective outcome that had to be detected as per the study protocol
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	Comment: This was an open‐label trial, and outcome assessors were not blinded. However the outcome of interest was an objective outcome, so the likelihood of detection bias is low.
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote “Four patients, 3 from ranitidine group, were excluded for technical reasons” Comment: Nearly 16% of randomised participants were excluded from analysis. An intention to treat analysis was not performed.This would have contributed to attrition bias
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes have been reported
Other bias	Low risk	Comment: Funding was provided by FAEPEX. Fundação de Apoio ao Ensino, à Pesquisa e à Extensão.However, the role of the sponsor in the conduct and reporting of the trial is unclear