Kaushal 2000.

Methods	Open‐label randomised controlled trial
Participants	Baseline characteristics Number randomised: 75 participants Number analysed: 75 participants Famotidine Age (years; mean (range)): 32.92 +/‐ 10.93 Number of participants (n): 25 Gender (male/female; n): 24/1 Sucralfate Age (years; mean (range)): 32.7 +/‐ 12.79 Number of participants (n): 25 Gender (male/female; n): 24/1 No prophylaxis Age (years; mean (range)): 36.34 +/‐ 15.58 Number of participants (n): 25 Gender (male/female; n): 24/1 Inclusion criteria Head injury of < 24 hours' duration Glasgow Coma Scale (GCS) score < 10 Need for nasogastric intubation Admitted to Neurosurgery Unit Informed consent (could not be taken directly from patients); it was taken from the next of kin Exclusion criteria History of acid peptic disease Upper GI bleed Use of ulcer‐modifying drugs over preceding 4 weeks Presence of significant hepatic/renal disease Bleeding diathesis or significant injury requiring anaesthesia Ventilation or surgery, except tracheostomy or minor wound suturing Baseline imbalances: Age, gender, and clinical features of participants in the 3 groups were comparable. Participants were people who required ICU care after head injury (mainly because if road side accident)
Interventions	Famotidine Dose (total/d): 40 mg Duration of treatment (days): ‐ Route: Intervention: prophylactic famotidine (20 mg) twice daily Concomitant medications: In case of 3 consecutive positive tests for occult blood in any group, the protocol allowed use of antacids in addition to drugs patients were already receiving Sucralfate Dose (total/d): 4 g Duration of treatment (days): ‐ Route: Intervention: prophylactic sucralfate 2g twice daily Concomitant medications: In case of 3 consecutive positive tests for occult blood in any group, the protocol allowed use of antacids in addition to drugs patients were already receiving No prophylaxis Dose (total/d): ‐ Duration of treatment (days): ‐ Route: Intervention: no regular prophylactic antiulcer treatment Concomitant medications: In case of 3 consecutive positive tests for occult blood in any group, the protocol allowed use of antacids plus famotidine (20 mg twice daily) or sucralfate (2 g twice daily) Adherence to regimen: Quote: "Out of 56 patients who had upper GI bleeding, 39 started bleeding within 3 days of head injury" Comment: Only 1 patient in the famotidine group required escape treatment as compared with 3 in the sucralfate group and 8 in the no prophylaxis group. The exact reason for escape of treatment is not mentioned but could be attributed to untimely death or upper GI bleed that was clinically significant as per the study protocol. The 56 participants with upper GI bleed are inclusive of all grades of bleeding according to the study protocol. Interventions were discontinued if at least 3 consecutive positive occult blood readings were detected Duration of trial: ‐ Duration of follow‐up: 15 days
Outcomes	Outcomes sought in review and reported in trial Primary outcomes Incidence of upper GI bleeding; haemorrhage was graded as grade 0 if test for occult blood was negative; grade 1 if test for occult blood was positive; grade 2 if there was also red or brown discolouration of the aspirate; and grade 3 if severity of haemorrhage necessitated blood transfusion Note: Among the 56 participants who bled, 39 of them started to bleed within 3 days of head injury. Data on occult bleeding were not used in the review Secondary outcomes All‐cause mortality in ICU Participants requiring blood transfusion (none) Units of blood transfused (no participant required this) Outcomes sought but not reported in trial Incidence of VAP All‐cause mortality in hospital Duration of ICU stay Duration of intubation Adverse events of interventions Outcomes reported in trial but not used in review Incidence of upper GI bleeding with respect to Glasgow Coma Scale (GCS)
Notes	Setting: Neurosurgery Unit of Medical College and Hospital, Ludhiana, India Source of funding: ‐ Ethics approval: Quote: "After approval from Hospital Ethics Committee, the study was conducted in 75 consecutive patients" Comment: The ethics committee of the concerned institution had approved the study Informed consent: Quote: "Since informed consent could not be taken directly from patients, it was taken from the next of kin" Comment: Informed consent was obtained Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: According to the study report, data on endoscopy could not be analysed because of small numbers of participants who underwent the procedure. Occult bleeding occurred in 38 participants (no prophylaxis: 11, famotidine: 12, and sucralfate: 15)
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 1 arm received no prophylaxis; this would not have made it possible to blind study personnel and participants
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: unclear whether outcome assessors were blinded. However GI bleeding was an objective outcome that was detected as per the definition in the study
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: unclear whether outcome assessors were blinded. All other outcomes of interest were objective in nature
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: All randomised participants were part of the final analysis in the study report
Selective reporting (reporting bias)	Low risk	Comment: The intended outcome of GI bleeding was reported in the study report
Other bias	Low risk	Comment: unclear on the source of funding. No other form of bias detected