Brophy 2010.

Methods	Quasi‐randomised trial
Participants	Baseline characteristics Number randomised: 51 participants Number analysed: 51 participants Famotidine Age (years; mean (SD)): 37 (17) Number of participants (n): 23 Gender (male/female; n): 20/3 Lansoprazole Age (years; mean (SD)): 43 (22) Number of participants (n): 28 Gender (male/female; n): 17/11 Inclusion criteria Admitted to neurosurgery ICU Prescribed stress ulcer prophylactic therapy during the study period Gastric pH < 4.0 before first dose of lansoprazole or famotidine One of the following risk factors for stress‐related mucosal disease (SRMD); head injury with altered mental status, acid–base disorder, multiple trauma, coagulopathy, multiple surgical procedures, hypotension > 1 hour, sepsis Exclusion criteria GI bleeding Prior use of an anti‐secretory agent during admission History of gastric or duodenal ulcer Age < 18 years Allergies to famotidine or lansoprazole; pregnancy Anticipated need for stress ulcer prophylaxis (SUP) for < 3 days (OR) Renal compromise (creatinine clearance < 50 mL/min) Baseline imbalances: "There were significantly more males than females in the study. Over 75% of the patients had a Glasgow Coma Scale (GCS) < 9, and median GCS scores were similar between the two groups. All of the patients had at least two risk factors for SRMD, and each treatment group had a similar number of patients with traumatic brain injuries. The median baseline gastric pH was 3.0 for both famotidine and lansoprazole groups" Comment: There were more women in the lansoprazole group than in the famotidine group
Interventions	Famotidine Dose (total/d): 60 mg Duration of treatment (days; mean (SD)): > 3 (‐) Route: IV or PO Intervention: 20 mg IV every 12 hours, or orally 20 mg every 12 hours after 72 hours Concomitant medications: Most patients in this study received enteral nutrition by day 2 Lansoprazole Dose (total/d): Duration of treatment (days, mean (SD)): > 3 (‐) Route: nasogastric tube Intervention: 30 mg suspended in 10 mL of an 8.4% sodium bicarbonate solution or apple juice, and administered via NG tube daily Concomitant medications: Most patients in this study received enteral nutrition by day 2 Adherence to regimen: ‐ Duration of trial: August 1999 to April 2005 Duration of follow‐up: “Patients were followed until 24 hours after the discontinuation of SUP, the patient was discharged from the ICU, or if the patient expired, whichever came first"
Outcomes	Outcomes sought in review and reported in trial Incidence of clinically significant bleeding related to SRMD defined as the presence of at least 1 of the following Endoscopic evidence of stress‐related mucosal bleeding Bright red blood per NG tube that did not clear after lavage Overt bleeding (haematemesis, bloody gastric aspirate, melena, or haematochezia) plus either a decrease in blood pressure of 20 mmHg or a decrease of 2 g/dL in haemoglobin and 2 units of blood transfused within 24 hours Adverse events of interventions Outcomes sought but not reported in trial VAP All‐cause mortality in ICU All‐cause mortality in hospital Duration of ICU stay Duration of intubation Number of participants requiring blood transfusion Number of units of blood transfused Outcomes reported in trial but not used in review • Duration of pH ≥ 4.0 • Percentage of time gastric residual was < 28 mL
Notes	Setting: The Virginia Commonwealth University (VCU), 1000‐bed, academic, level 1 trauma centre Source of funding: Quote: "This study was funded by TAP Pharmaceuticals" Conflicts of interest: ‐ Ethics approval: Quote: "The Virginia Commonwealth University (VCU) Institutional Review Board approved this study prior to subject enrolment, and this study was conducted in compliance with the Declaration of Helsinki" Informed consent: Quote: "All subjects provided written informed consent prior to study commencement" Clinical trials registration: ‐ Sample size calculation: Quote: "...we assumed that on day 3 of therapy, 85% of the patients receiving lansoprazole would have pH values ≥ 4.0 for 80% of the time compared to only 40% of the patients receiving famotidine. Using these proportions, α = 0.05, β = 0.20, and a two‐way statistical test, approximately 22 patients were needed in each group to show statistical significance" Comment: This was after 30 people admitted to the neurosurgical unit were followed; it was assumed that approximately 40% of them receiving famotidine and 80% receiving lansoprazole maintained gastric pH ≥ 4 80% of the time
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "Patients admitted into the unit during odd‐numbered months received famotidine 20 mg IV every 12 hours; patients admitted during even numbered months received lansoprazole" Comment: This was a quasi‐randomised trial in which sequence generation was not done
Allocation concealment (selection bias)	High risk	Quote: "Patients admitted into the unit during odd‐numbered months received famotidine 20 mg IV every 12 hours; patients admitted during even numbered months received lansoprazole" Comment: This was a quasi‐randomised trial in which allocation was not concealed
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: This was not a placebo‐controlled trial; the different interventions and their mode of administration could not have made it possible to blind trial personnel
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: This was an unblinded trial in which GI bleeding was detected as per the definition used in the trial protocol
Blinding (detection bias) Nosocomial pneumonia	Unclear risk	Comment: Trial did not address this outcome
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: This was an unblinded trial; outcomes of interest were diagnosed as described in the trial protocol
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: All randomised participants were part of the final analysis. Therefore, no attrition bias is suspected
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported
Other bias	Low risk	Comment: TAP Pharmaceuticals funded the trial. The role of the sponsor in the conduct and reporting of the trial is unclear. No other sources of bias are suspected