Stothert 1980.

Methods	Single‐blind randomised controlled trial
Participants	Baseline characteristics Number randomised: 144 participants Number analysed: 123 participants Antacids Age (years; mean (SD)): 47 (‐) Number of participants (n): 58 Gender (male/female; n): 41/17 Cimetidine Age (years; mean (SD)): 43 (‐) Number of participants (n): 65 Gender (male/female; n): 48/17 Inclusion criteria ‐ Exclusion criteria Diagnosis of gastric haemorrhage Failure to follow the outlined protocol Baseline imbalances: Quote: "No significant difference exists between the groups in relation to the risk factors such as abdominal trauma, cardiovascular disease, respiratory failure, sepsis, neurologic injury, orthopedic injury, vascular injury, renal failure, hepatic failure, alcohol or drug abuse, metastatic carcinoma, hypotension and history of peptic ulcer. Similarly, the two groups are quite comparable in age and sex ratio" Comment: There was no significant difference between the 2 groups with respect to demographic and baseline risk factors. Nine and 6 participants in both groups had a history of ulcers
Interventions	Antacids Dose (total/d): 720 cc Duration of treatment (days): until the patient no longer required gastric decompression or was discharged from the intensive care unit as a result of improvement or death Route: NG or gastrostomy tube Intervention: 30 cc of Mylanta II every hour via the nasogastric or gastrostomy tube. The tube was subsequently clamped for 30 minutes and then placed on suction for 30 minutes. If the pH < 4 at the end of 3 of 6 consecutive hourly time periods, the amount of Mylanta II was increased to 60 cc/h. Similarly, if pH control failed at this level, the amount of antacid was increased to 90 cc/h and finally to 120 cc/h if required. Any patient who required more than 120 cc/h of antacid then had cimetidine added to the protocol. Any patient developing severe diarrhoea (defined as greater than 4 loose stools per day) while on Mylanta II underwent substitution of the antacid with Alternagel Concomitant medications: Each participant remained NPO for the duration of the study Cimetidine Dose (total/d): 1200 mg Duration of treatment (days): until the patient no longer required gastric decompression or was discharged from the intensive care unit as a result of improvement or death Route: IV Intervention: Cimetidine was administered using an initial dosage level of 300 mg every 6 hours and was continued at this rate if the intragastric pH > 4. If this pH was not achieved, the frequency of drug administration was increased to every 4 hours, and then to every 3 hours. Criteria for failure at a given dose included a pH < 4 for 3 out of 6 consecutive hourly measurements. Maximum dose was 2400 mg per 24 hours. Any patient who failed all 3 dosage levels then had antacid added to the cimetidine regimen according to the antacid protocol Concomitant medications: Each participant remained NPO for the duration of the study Adherence to regimen: Quote: "One hundred forty‐four patients were included in this study. Fifty‐eight patients were randomised to the antacid treatment group and 65 patients were randomised to the cimetidine therapy group. Forty‐six patients were not included in these results because they met protocol criteria for less than 24 hours. Twenty‐one patients required no therapy because of persistent pH ≥ 4. Forty‐eight (74%) cimetidine recipients had the expected elevation of pH ≥ 4. Seventeen (26%) failed despite maximum dosage of cimetidine. All failures with cimetidine had antacids added and responded successfully. No failure of antacid therapy was seen in this study and therefore no patients crossed over from the antacid therapy group into the cimetidine therapy group.The twenty‐one patients who maintained a gastric pH ≥ 4 required no prophylaxis and were not further dealt with further in this paper. All studies continued until the patient no longer required gastric decompression or was discharged from the intensive care unit as a result of improvement or death" Comment: also stated that all patients responded to antacid therapy "Forty participants responded to 30 cc every hour to maintain gastric pH at the desired level. Only three patients required 120 cc per hour to maintain this level. In the group receiving cimetidine, 34% responded to 300 mg every six hours. An additional 40% of the participants responded to administration at a dosage level of every four or every three hours" Duration of trial: October 1978 to July 1979 Duration of follow up: not clearly mentioned in the study report. Probably until death or discharge
Outcomes	Outcomes sought in review and reported in trial (none of these were primary outcomes of the study) Incidence of GI bleeding defined as occurrence of melena or bright red bleeding from NG tube that would not clear with iced saline lavage All‐cause mortality in ICU Participants requiring blood transfusions Adverse events of interventions Outcomes sought but not reported in trial Incidence of ventilator‐associated pneumonia Duration of ICU stay Duration of intubation All‐cause mortality in hospital Units of blood transfused Outcomes reported but not used in review Intragastric pH status
Notes	Setting: Harborview Medical Center Surgical Intensive Care Unit (SICU), 325 Ninth Avenue, Seattle, WA 98104 Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: ‐ Informed consent: ‐ Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: It is mentioned that diarrhoea occurred in 5 of the 75 participants treated with antacids. This included 58 antacid‐treated participants and 17 participants in whom cimetidine "failed" as per the study protocol. These data are unclear on the incidence in the original denominator, so could not be analysed
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The randomisation process was based on a random number table in a blinded fashion" 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. However, the baseline there is no imbalance in baseline characteristics, indicating low risk of selection bias
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Day‐to‐day clinical management was performed by an attending physician independent of the study protocol" Comment: Personnel were blinded
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: no clear mention of blinding of outcome assessors. GI bleeding was an objective outcome detected as per the definition in the study protocol
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: All other outcomes of interest were objective in nature
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: A per‐protocol analysis was performed to measure the outcomes of interest. Only 123 of 144 participants were accounted for in the analysis. Groups to which these 67 participants were randomised remains unclear. However, there is no imbalance between groups with respect to the number of participants available for final analysis
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes stated were analysed and reported
Other bias	Low risk	Comment: source of funding not clear. No other known form of bias detected