Ephgrave 1998.

Methods	Double‐blind randomised controlled trial
Participants	Baseline characteristics Number randomised: 140 participants Number analysed: 140 participants Antacids Age (years; mean (range)): ‐ Number of participants (n): 70 Gender (male/female; n): ‐ Sucralfate Age (years; mean (range)): ‐ Number of participants (n): 70 Gender (male/female; n): ‐ Inclusion criteria Participants at the Veterans Affairs Medical Center, Iowa City, Iowa, scheduled for major elective surgical procedures requiring postoperative nasogastric intubation Exclusion criteria Participants who did not give informed consent Baseline imbalances: Quote: "The patients who were randomly assigned to receive antacid or sucralfate stress ulcer prophylaxis were similar in most risk factors for postoperative complications but they differed in the percentage of patients with a history of treatment for chronic obstructive pulmonary disease (COPD). Significantly more patients with a clinical diagnosis of COPD preoperatively were randomly assigned to receive sucralfate (COPD was found to be an independent risk factor for development of pneumonia)" Comment: Baseline age and gender distributions are not mentioned; however the distribution of all risk factors except COPD is normal across the 2 groups. Most participants from both groups were admitted for general surgery of the abdomen (23 in antacid group and 27 in sucralfate group, respectively)
Interventions	Antacid Dose (total/d): max 180 mL Duration of treatment (days): "One hundred twenty‐two participants received 3 or more days of stress ulcer prophylaxis with the study drugs, while only 25 received 7 or more days" Route: PO or NG tube (unclear) Intervention: double‐strength antacids (15 mL every 2 hours while in the intensive care unit, every 4 hours after transfer to the surgical ward) + sham sucralfate preparation Concomitant medications: enteral nutrition in 21%; gastric pH was monitored hourly while patient was in the intensive care unit, and administration of the antacid (or sham antacid) was repeated after 1 hour if pH persisted at < 4.0. Antibiotics (IV; all patients for wound infections). Antibiotic orally + bowel preparation was given to 35% of participants overall Sucralfate Dose (total/d): 4 g Duration of treatment (days): "One hundred twenty‐two participants received 3 or more days of stress ulcer prophylaxis with the study drugs, while only 25 received 7 or more days" Route: PO or NG tube (unclear) Intervention: sucralfate suspension (1 g in 10 mL every 6 hours) + sham antacid preparation Concomitant medications: enteral nutrition in 20%; gastric pH was monitored hourly while patient was in the intensive care unit, and administration of antacid (or sham antacid) was repeated after 1 hour if pH persisted at < 4.0. Antibiotics (IV; all patients for wound infections). Antibiotic orally + bowel preparation was given to 35% of participants overall Adherence to regimen: Quote: "One hundred twenty‐two participants received 3 or more days of stress ulcer prophylaxis with the study drugs, while only 25 received 7 or more days.Many patients were treated with intravenous H2‐receptor blockers after 3 days postoperatively, which was when the study drugs were generally discontinued" Duration of trial: June 1990 to April 1992 Duration of follow‐up: Quote: "Daily assessment for gastrointestinal tract bleeding, infections, and other postoperative complications was continued until discharge from the hospital or death for all 140 patients"
Outcomes	Outcomes sought in review and reported in trial Incidence of GI bleeding defined as appearance of grossly bloody fluid in the nasogastric aspirate that failed to clear with 100‐mL saline lavage Incidence of pneumonia diagnosed by consensus of 2 investigators not involved with clinical care by means of the following criteria: a new or progressive infiltrate on chest roentgenogram, plus 3 of the following: Purulent sputum with more than 25 white blood cells per high‐power field Isolation of respiratory pathogens from an adequate sputum sample Peripheral leucocytosis Temperature > 38.3°C All‐cause mortality in ICU Outcomes sought but not reported in trial All‐cause mortality in hospital Duration of ICU stay Duration of intubation Number of participants requiring blood transfusion Number of units of blood transfused Adverse events to interventions Outcomes reported in trial but not used in review Intragastric pH values Infections; wound/urinary tract Drug effects on microbial appearance and transmission Intubation time (only mean number of days, SD not provided)
Notes	Setting: The Surgical Service, Veterans Affairs Medical Center, Iowa City, Iowa Source of funding: Quote: "This study was funded through a Veterans Affairs Merit Review grant." Conflicts of interest: ‐ Ethics approval: Quote: "...approved for human subjects by the appropriate committees of the University of Iowa College of Medicine and the Iowa City Veterans Affairs Medical Center" Informed consent: Quote: "Patients were contacted before their elective surgical procedures, and less than 10% of the patients asked to participate refused to do so. Patients who declined entry into the study were not monitored further" Clinical trials registration: ‐ Sample size calculation: Quote: "A biostatistician  calculated that an 80% likelihood of detection of a 50% improvement in the expected postoperative pneumonia rate of 15% to 20% would require entry of more than 300 patients into each arm of the study. With pilot work showing that more than 50% of patients in the surgical intensive care unit harboured pathogens in their gastric contents, we determined that approximately 70 patients in each arm would give an 80% likelihood of detecting an effect by the stress ulcer prophylactic agent on the gastric microbial flora" Comment: Sample size was calculated for the primary endpoint of pneumonia Additional notes: Study endpoints of pneumonia and GI bleeding were diagnosed postoperatively. Many participants received H2 antagonists 3 days postoperatively; study drugs were discontinued by then. Pulmonary colonisation with gastric micro‐organism occurred in 16% of antacid‐treated and 15% of sucralfate‐treated participants
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was performed in blocks of 20 patients before the study began, to ensure that both treatment groups would be evenly represented throughout the 2 years of patient accrual" Comment: Method adopted to obtain random sequence generation is clearly mentioned in the study report
Allocation concealment (selection bias)	Low risk	Quote: "In keeping with the double‐blind design, the treatment group assignment of each patient was known only to the pharmacy service until all the clinical and microbial data collection was complete" Comment: Allocation concealment was done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The sham agents were designed to be similar in colour and viscosity to the active agents, and free of acid‐neutralizing properties" Comment: This was a double‐blind study in which participants and trial personnel appear to be blinded. Therefore the likelihood of performance bias is low
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Quote: "The sham agents were designed to be similar in colour and viscosity to the active agents, and free of acid‐neutralizing properties" Comment: This was a double‐blind study in which participants and trial personnel appear to be blinded. Moreover the outcome of GI bleed was detected as per the definition in the study protocol owing to the objective nature of the outcome
Blinding (detection bias) Nosocomial pneumonia	Low risk	Quote: "Pneumonia was diagnosed by consensus of 2 investigators not involved with the clinical Care”; "The sham agents were designed to be similar in colour and viscosity to the active agents, and free of acid‐neutralizing properties" Comment: Blinding of outcome assessors was done. Moreover the outcome of pneumonia was detected as per the definition in the study protocol owing to the objective nature of the outcome
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Quote: "The sham agents were designed to be similar in colour and viscosity to the active agents, and free of acid‐neutralizing properties" Comment: Blinding of outcome assessors was done. Moreover because of the objective nature of the outcomes, the likelihood of detection bias is low
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: All randomised participants were analysed for the outcomes of interest
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes have been reported
Other bias	Low risk	Comment: Funding was through a Veterans Affairs Merit Review grant. The role of the sponsor in the conduct and reporting of the trial is unclear. No other bias was detected