Prakash 2008.

Methods	Open‐label randomised controlled trial
Participants	Baseline characteristics Number randomised: Unclear Number analysed: 50 participants Ranitidine Age (years; mean (SD)): 35.12 (14.10) Number of participants (n): 25 Gender (male/female; n): 19/6 Sucralfate Age (years; mean (SD)): 27.48 (16.64) Number of participants (n): 25 Gender (male/female; n): 13/12 Inclusion criteria Admitted to the adult ICU Receiving mechanical ventilation for at least 24 hours Having a nasogastric tube in place Having an expected ICU stay of at least 3 days Exclusion criteria Anticipated to require mechanical ventilation for less than 24 hours, Receiving antacids, H2 blockers or sucralfate within the previous 48 hours Active GI bleeding Evidence of infiltrates on the chest radiograph at the time of admission Taking steroids Having undergone gastric or oesophageal surgery Pregnancy Baseline imbalances: Quote: "There were no significant differences between the groups with respect to age, sex, distribution of underlying diseases, the severity of illness, prophylactic antibiotic therapy, and gastric pH at admission" Comment: no significant difference between the 2 groups with respect to demographic and baseline risk factors. Laparotomy was the most common cause for admission in both groups. The APCHE II score was 14.21 ± 5.44 and 13.34 ± 6.03 in the ranitidine and sucralfate groups, respectively
Interventions	Ranitidine Dose (total/d): 200 mg Duration of treatment (days): ‐ Route: IV Intervention: 50 mg administered intravenously every 6 hours Concomitant medications: ‐ Sucralfate Dose (total/d): 4 g Duration of treatment (days): ‐ Route: NG tube Intervention: sucralfate administered as 1 g of suspension diluted in 20 mL sterile water through a nasogastric tube every 6 hours. The nasogastric tube was flushed with 10 mL sterile water and clamped for 30 minutes after instillation Concomitant medications: ‐ Adherence to regimen: Quote: "Seven patients were extubated and one patient died before four days of observation and could not be analysed for the development of late onset pneumonia. 42 patients observed for more than four days" Comment: Of the initial number of participants who were randomised, only those who were eventually intubated for longer than 24 hours were part of the study analysis Duration of trial: ‐ Duration of follow‐up: Patients were followed up for a period of 7 days with daily chest radiograph, complete blood count with differential, serum electrolytes, and gastric pH measurements
Outcomes	Outcomes sought in review and reported in trial Primary outcomes Incidence of ventilator‐associated pneumonia defined as an infiltrate on chest X‐ray plus three of the following criteria Leucocytosis > 10,000 cells/mm³ Pathogenic bacteria on a tracheal or blood culture Gram stain of tracheal aspirate showing moderate to heavy bacteria or polymorphs‐neutrophils > 25/HPF Temperature > 38ºC, using the criteria of Langer and colleagues 15 early‐onset and late‐onset cases of pneumonia were diagnosed if they occurred during the first 4 days of or 4 days after initiation of mechanical ventilation, respectively. Patients observed for longer than 4 days and were evaluated for the development of late‐onset pneumonia Secondary outcomes Significant upper GI bleeding defined as considered to be present in the event of haematemesis, melena, haematochezia, or fresh blood per nasogastric tube, which did not clear after lavage with 500 mL sterile saline Participants requiring blood transfusions (no participant required blood transfusions) All‐cause mortality in ICU Outcomes sought but not reported in trial Duration of ICU stay Duration of intubation Adverse events of interventions Outcomes reported but not used in review Gastric colonisation Intragastric pH values
Notes	Setting: Department of Anaesthesia and Intensive Care, Vardhman Mahavir Medical College and Safdarjang Hospital, New Delhi Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: Quote: "The study protocol was approved by the institutional ethics committee" Informed consent: Quote: "...informed consent was obtained from the patients or, if this was not possible because of the clinical condition, from a relative of the family" Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: Of the 25 participants who developed pneumonia, 11 (44%) had the source traced to gastric colonisation (10 in ranitidine and 1 in sucralfate group). Klebsiella species was the most commonly isolated (gastric and tracheal aspirates). Late‐onset pneumonia was more common in the ranitidine group than in the sucralfate group (10 and 2; P = 0.001), and there was no significant difference in early‐onset pneumonia between the 2 groups (5 and 8; P = 0.098)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was done using a computer generated random number table" Comment: 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: no clear mention of blinding the outcome assessor to this outcome. But GI bleeding was an objective outcome detected as per the definition in the study report
Blinding (detection bias) Nosocomial pneumonia	Low risk	Quote: "Chest radiographs were interpreted by a radiologist who had no knowledge of the patients’ treatment group after randomisation" Comment: VAP was detected as per the definition in the study report, and the radiologist was blinded to the interventions
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: no clear mention of blinding outcome assessors. However, outcomes were objective in nature, so the likelihood of detection bias is low
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: Although 50 participants in each treatment arm were evaluated, we are not sure of the number of participants who were initially randomised to each of these arms
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported
Other bias	Low risk	Comment: The source of funding is not mentioned. No additional biases were detected