Ryan 1993.

Methods	Single‐blind randomised controlled trial
Participants	Baseline characteristics Number randomised: 114 participants Numner analysed:114 participants Cimetidine Age (years; mean (range)): 65 (17‐96) Number of participants (n): 56 Gender (male/female; n): 34/22 Sucralfate Age (years; mean (range)): 62 (17‐90) Number of participants (n): 58 Gender (male/female; n): 37/21 Inclusion criteria Admitted to ICU Age > 16 years Endotracheal intubation Presence of nasogastric tube Expected survival longer than 24 hours, which was based on mortality probability model (MPM), which used the following criteria: age, history of chronic renal insufficiency, admission to an ICU in the previous 6 months, cardiopulmonary resuscitation within previous 24 hours, elective and emergency ICU admission, malignancy as an active problem in the past 6 months, probable infection, level of consciousness, systolic blood pressure, heart rate, and surgical or medical care Exclusion criteria Admission for upper GI haemorrhage Admission for pneumonia Previous gastric surgery Treatment with H2 antagonists, antacids, and sucralfate within previous 48 hours Baseline imbalances: Quote: "There was no significant difference in mean age, sex ratio, or number of patients admitted to medical or surgical services" Comment: The 2 groups were similar with respect to their baseline characteristics
Interventions	Cimetidine Dose (total/d): varies Duration of treatment (days): ‐ Route: IV Intervention: continuous infusion, using 300‐mg bolus followed by 37.5 mg/g Concomitant medications: intragastric feeding for 25 participants, antibiotic therapy, steroid therapy Sucralfate Dose (total/d): 4 g Duration of treatment (days): ‐ Route: NG tube Intervention: administered by nasogastric tube, at a dose of 1 g every 6 hours, suspended in 20 mL of sterile water, flushed through with 10 mL of water Concomitant medications: intragastric feeding for 27 participants, antibiotic therapy, steroid therapy Adherence to regimen: 114 participants who met the inclusion criteria were enrolled into the study. 25 (22%; 12 participants from cimetidine group and 13 participants from sucralfate group) participants were withdrawn from the study for the following reasons: Extubation within 48 hours after enrolment and discharge from ICU (n = 2) NG tube was removed (n = 2) At the request of participant or guardian (n = 3) Died within 48 hours (n = 8) Inadvertent medication change (n = 4) Adverse drug reaction (2 in cimetidine and 1 in sucralfate groups) (n = 3) Documented case of aspiration by a witness (n = 3) The remaining 89 participants constituted the study group Duration of trial: January 2009 to September 2009 Duration of follow‐up: ‐
Outcomes	Outcomes sought in review and reported in trial Primary outcomes Incidence of nosocomial pneumonia diagnosed based on the Center for Disease Control and Prevention Guidelines (CDC), which include rales or dullness to percussion or bronchial breath sounds on physical examination of the chest, and any of the following: New onset of purulent sputum or change in the character of sputum Organism isolated from blood culture Isolation of pathogen from the specimen obtained from endotracheal aspirate, bronchial brushing, or biopsy Note: Other than the CDC and prevention criteria, each participant was required to have 2 chest roentgenograms showing persistent infiltrates, with agreement by intensivist and radiologist Secondary outcomes Incidence of GI haemorrhage: presence of fresh blood or 'coffee grounds' in nasogastric aspirate, which tested positive with Hemoccult test and persisted after 100 mL of saline lavage All‐cause mortality in ICU Duration of intubation Participants requiring blood transfusion Adverse events of interventions Outcomes sought but not reported in trial Duration of ICU stay All‐cause mortality in hospital Units of blood transfused Outcomes reported in report but not used in review Pathogens isolated from participants who developed pneumonia
Notes	Setting: Medical and Surgical Intensive Care Unit, Springfield, Mass, Tufts University Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: Quote: "The study was approved by the institutional review board" Informed consent: Quote: "Informed consent was obtained from each patient or guardian" Clinical trials registration: ‐ Sample size calculation: ‐
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: ”Patients were randomised according to computer generated numbers to receive either cimetidine or sucralfate” Comment: The 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 study interventions would not have made it possible to blind study personnel and participants
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: Outcome assessors were not blinded, but GI bleeding was an objective outcome detected as per the definition in the study protocol
Blinding (detection bias) Nosocomial pneumonia	Low risk	Quote: "The radiologist and the intensivist who assessed the chest roentgenograms for diagnosing pneumonia were both blinded to the treatment that the participant was receiving" Comment: Nosocomial pneumonia was detected as per the definition in the study protocol by an outcome assessor who was blinded to participant data
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: unclear on the blinding of outcome assessors. However, outcomes of interest were objective in nature
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "...with 10 mL of water. Twenty‐five patients (22%) were withdrawn from the study for the following reasons: two because of extubation within 48 hours of enrolment and discharge from the ICU, two because the nasogastric tube was removed (the nasogastric tube was required to instil sucralfate into the stomach and monitor bleeding), three at the request of the patient or guardian, eight because they died within 48 hours, four because of inadvertent medication change, three because of documented cases of aspiration by a witness, three because of adverse reactions from medications (two patients in the cimetidine group had confusion and neutropaenia, and one patient in the sucralfate group could not tolerate the nasogastric tube clamped). The patients who were withdrawn were equally distributed between the two treatment groups. The remaining 89 patients constituted" Comment: no incomplete reporting of outcomes suspected
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported
Other bias	Low risk	Comment: Source of funding is not clearly mentioned in the study design. No other sources of bias suspected