Hastings 1978.

Methods	Parallel‐group randomised controlled trial
Participants	Baseline characteristics Number randomised: 100 participants Number analysed: 100 participants Antacids Age (years; mean (range)): 60.7 Number of participants (n): 51 Gender (male/female; n): 31/20 No prophylaxis Age (years; mean (range)): 62.3 Number of participants (n): 49 Gender (male/female; n): 20/29 Inclusion criteria Informed consent given by the physician and a relative or themselves Hospitalised in the Respiratory‐Surgical Intensive Care Unit of the Beth Israel Hospital during the study period Diagnosed with multiple trauma, major operative procedures, respiratory failure, vital capacity < 10 mL/kg, ratio of dead space to tidal volume > 0.6 or alveolar hypoventilation with arterial pH < 7.25, hypotension (defined as systolic pressure < 100 mmHg for longer than 2 hours before and after randomisation), sepsis (including participants with peritonitis, proved bacteraemia or the complex of fever, elevated white cell count, and hypotension with proved bacteriologic source), jaundice, and renal failure Exclusion criteria Receiving fluids or food by mouth Having undergone gastric, cardiac, or oesophageal operations Primary disease was burn trauma or neurological disease Evidence of gross upper GI bleeding Baseline imbalances: Quote: "Fifty one of the 100 participants entered into the study were randomised to receive antacid prophylaxis. Six major risk factors were analysed for each participant in each group. These risk factors were respiratory failure, extra abdominal sepsis, peritonitis, jaundice, renal failure and hypotension. There were 110 risk factors in 51 participants in the antacid group, a mean of 2.2 risk factors per participant. There were 115 risk factors in 49 participants in the group not receiving antacid prophylaxis, a mean of 2.4 risk factors per participant. All participants in respiratory failure were treated with constant‐volume ventilators. The severity of respiratory failure was judged by the alveolar‐ atrial oxygen. The mean highest value was 363+/‐ 25 mm Hg (SEM) in the participants receiving antacid and 324+/‐ 29 mm Hg in those not receiving Antacid prophylaxis (p > 0.05). The difference in mean blood urea nitrogen values (96+/‐ 10 mm/dl in the Antacid group vs. 90+/‐ 10 mm Hg in those not receiving antacid prophylaxis) was not statistically significant between the two groups. The extent of jaundice was also similar in the two groups" Comment: Both groups were similar with respect to their baseline characteristics. The major risk factor was respiratory failure
Interventions	Antacids Dose (total/d): 720 mL Duration of treatment (days): 2.6 Route: IV Intervention: Mylanta II in 46 participants and aluminium hydroxide in 5 participants: 30 mL at the beginning, at the end of each hour. 30 mL of antacids was instilled at the beginning of each subsequent hour, provided gastric pH was ≥ 3.5. If pH < 3.5, 60 mL of antacid was instilled. The nasogastric tube was flushed with 10 mL of tap water after each instillation, to ensure complete delivery. Then the tube was clamped for 60 minutes Concomitant medications No prophylaxis Dose (total/d): ‐ Duration of treatment (days): 3.1 Route: IV Intervention: ‐ Concomitant medications: ‐ Adherence to regimen: Quote: "The study was ended when oral feedings were begun and the nasogastric tube was removed, or the participant was discharged from the intensive care unit" Comment: In 2 participant who had diarrhoea, antacid was stopped, and in 2 other participants, a different antacid was administered. In 1 participant from antacid group with elevated magnesium levels, antacid was changed to a preparation that did not contain magnesium Duration of trial: March 1972 to March 1977 Notes duration of treatment: Mean duration for the entire study of 100 participants was 2.9 ± 0.29 days (SEM). Study was terminated when oral feedings were begun and the nasogastric tube was removed, or when the participant was discharged from the ICU Duration of follow‐up: ‐
Outcomes	Outcomes sought in review and reported in trial Primary outcome (outcomes are not categorised as primary and secondary, but from the study report we feel GI Bleeding was the primary outcome) Incidence of acute GI bleeding. Gastric aspirate was checked for frank or occult blood every 4 hours with the bench guaiac test or the haemoccult paper test. Any participant who had frank blood in his aspirate or had a 4+ positive guaiac test or a uniformly dark blue reaction with the haemoccult paper test on 3 consecutive readings was considered to have GI bleed, and prophylaxis was considered a failure Number of participants requiring blood transfusion Adverse reactions of interventions All‐cause mortality in ICU Outcomes sought but not reported in trial report Incidence of ventilator‐associated pneumonia All‐cause mortality in hospital Duration of ICU stay Duration of intubation Outcomes reported in report but not used in review Intragastric pH status Number of units of blood transfused (number provided, not mean or SD)
Notes	Setting: Respiratory‐Surgical Intensive Care Unit of the Beth Israel Hospital, 300 Brookline Avenue, Boston, MA, 02215 Source of funding: Quote: "we are indebted to Stuart Pharmaceuticals, Division of I.C.I United States, Inc., Wilmington, DE (manufacturers of Mylanta II), whose generous contribution in part made this study possible…" Conflicts of interest: ‐ Ethics approval: Quote: "The study was approved by the Committee on Cliniccal Investigations, New procedures and new forums of therapy of the Beth Israel Hospital" Informed consent: ‐ Clinical trials registration: ‐ Sample size calculation: ‐
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "…the patients were randomised by a table of random numbers" Comment: Method adopted to obtain random sequence generation is clearly mentioned in the study report
Allocation concealment (selection bias)	Unclear risk	Comment: not enough information on allocation concealment reported
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 the study interventions would not have made it possible to blind study personnel and participants
Blinding (detection bias) Clinically important upper GI bleeding	High risk	Comment: no clear definition for the diagnosis of upper GI bleeding or blinding of outcome assessors reported
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: All randomised participants were part of the analysis. Therefore there is no attrition bias
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported in the study
Other bias	Low risk	Quote: "we are indebted to Stuart Pharmaceuticals, Division of I.C.I United States ,Inc., Wilmington, DE (manufacturers of Mylanta II), whose generous contribution in part made this study possible…" Comment: The above mentioned organisation also manufactured the antacid used as intervention in this study, which is suggestive of potential conflict of interest. The role of the sponsor in the conduct and reporting of the trial is unclear. No other sources of bias are suspected