Lee 2014.

Methods	Parallel‐group randomised controlled trial
Participants	Baseline characteristics Number randomised: 60 participants Number analysed: 60 participants Esomeprazole Age (years; mean (SD)): 56.2 (18.4) Number of participants at baseline (n): 30 Gender (male/female; n): 20/10 Famotidine Age (years; mean (SD)): 59.2 (15.0) Number of participants at baseline (n): 30 Gender (male/female; n): 16/14 Inclusion criteria Age ≥ 18 years Admitted to ICU or management of severe cerebrovascular accident Exclusion criteria Age < 18 years History of allergy to either famotidine or esomeprazole Feeding through a nasogastric tube not possible Having gastrointestinal bleeding on admission Baseline imbalances: no significant difference for sex, age, GCS, AP‐II, intracranial pressure, and operation time between these 2 groups
Interventions	Esomeprazole Dose (total/d): 40 mg Duration of treatment (days): 7 Route: nasogastric tube Intervention: 40 mg (Nexium, AstraZeneca, Sodertaije, Sweden) dissolved in water through a nasogastric tube once per day for 7 days Concomitant medications: Every patient received ventilator support and nasogastric feeding when admitted to the ICU Famotidine Dose (total/d): 40 mg Duration of treatment (days): 7 Route: IV Intervention: intravenous famotidine (20 mg, Gaster, Astellas, Shizuoka, Japan) infusion every 12 hours for 7 days Concomitant medications: Every patient received ventilator support and nasogastric feeding when admitted to the ICU Adherence to regimen: ‐ Duration of trial: March 2007 to March 2010 Duration of follow‐up: 30 days
Outcomes	Outcomes sought in review and reported in trial GI bleeding (overt or occult) defined as tarry stool, haematemesis, drainage of more than 60 mL 'coffee ground' substance from nasogastric tube, or decreased haemoglobin level > 2 g/dL with proven lesions by endoscopic examination. We also defined positive stool occult blood test as occult bleeding Ventilator‐associated pneumonia defined as pneumonia occurring after 48 hours of ventilator use that fulfils ≥ 3 of the following 4 criteria: (1) presence of persistent (> 48 hours) or new‐onset infiltration in CXR; (2) positive sputum smear (with < 10 epithelial cells per low‐power field, 100×, and > 25 white blood cells per low‐power field or presence of polymorphonuclear cells with phagocytosis); (3) fever with body temperature > 38.3°C; and (4) leucocytosis > 12 × 109/L Mortality (30 days) Duration of ICU stay Outcomes sought in review but not reported in trial Blood transfusion Adverse events of interventions Duration of intubation Outcome reported in trial but not used in review 30‐Day survival
Notes	Setting: Neurosurgical ICU, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei, Taiwan Source of funding: Quote: "This study was performed in the Far Eastern Memorial Hospital and was supported by the research grant FEMH‐94‐C‐016 from the Far Eastern Memorial Hospital" Conflicts of interest: Quote: "All contributing authors declare no conflicts of interest" Ethics approval: Quote: "This study was approved by the Research Ethics Review Committee of the Far Eastern Memorial Hospital" Informed consent: Quote: "After explaining the study purpose and obtaining written consent from their family members" Clinical trials registration: ‐ Sample size calculation: ‐ Sponsorship source: supported by the research grant FEMH‐94‐ C‐016 from the Far Eastern Memorial Hospital
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The patients were randomly allocated to two groups" Comment: not enough details reported
Allocation concealment (selection bias)	Unclear risk	Comment: no details reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Comment: no details on blinding reported, but lack of blinding is unlikely to introduce bias to the outcomes or outcome measures
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Quote: "[We] defined upper gastrointestinal bleeding as tarry stool, haematemesis, drainage of more than 60 mL coffee ground substance from nasogastric tube, or decreased haemoglobin level more than 2 g/dL with proved lesions by endoscopic examination. We also defined positive stool occult blood test as occult bleeding" Comment: Outcome was measured objectively
Blinding (detection bias) Nosocomial pneumonia	Low risk	Quote: "We defined ventilator‐associated pneumonia as pneumonia occurring after 48 hours of ventilator use that fulfils three or more of the following four criteria: (1) presence of persistent (> 48 hours) or new onset infiltration in CXR; (2) positive sputum smear (with < 10 epithelial cells per low‐power field, 100×, and > 25 white blood cells per low‐power field or presence of polymorphonuclear cells with phagocytosis); (3) fever with body temperature > 38.3°C; and (4) leukocytosis > 12 × 10⁹/L" Comment: Outcome was measured objectively
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Unclear risk	Comment: no details reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: no incomplete outcome data; all participants randomised at baseline were included in analyses
Selective reporting (reporting bias)	Low risk	Comment: no incomplete reporting of outcomes suspected. All outcomes listed in the Methods section were also reported in the Results section
Other bias	Low risk	Comment: no other sources of bias suspected