REVISE TRIAL

Population:
Critically ill adults undergoing invasive mechanical ventilation in the ICU.

Intervention:
Intravenous pantoprazole at a dose of 40 mg daily.

Comparison:
Matching placebo.

Outcome:

• Primary Efficacy Outcome: Clinically important upper gastrointestinal bleeding.

• Primary Safety Outcome: Death from any cause at 90 days.

• Key Secondary Outcomes: Ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding.

Study Methods

• Design: International, randomized, blinded trial.

• Participants: 4821 patients from 68 ICUs in various countries.

• Duration: 90 days follow-up.

• Randomization: Patients assigned to pantoprazole or placebo groups.

• Blinding: Trial-group assignments were blinded to patients, their families, clinical and research staff, outcome adjudicators, and biostatisticians.

Results

• Clinically Important Upper Gastrointestinal Bleeding: Occurred in 25 of 2385 patients (1.0%) in the pantoprazole group and 84 of 2377 patients (3.5%) in the placebo group (HR, 0.30; 95% CI, 0.19 to 0.47; P<0.001).

• Death from Any Cause at 90 Days: Reported in 696 of 2390 patients (29.1%) in the pantoprazole group and 734 of 2379 patients (30.9%) in the placebo group (HR, 0.94; 95% CI, 0.85 to 1.04; P=0.25).

• Secondary Outcomes:Ventilator-associated pneumonia: Similar in both groups (23.2% vs. 23.8%).
  C. difficile infection: Slightly higher in the pantoprazole group (1.2% vs. 0.7%).
  Patient-important bleeding: Reduced in the pantoprazole group (1.5% vs. 4.2%; HR, 0.36; 95% CI, 0.25 to 0.53; P<0.001).

Conclusions

Pantoprazole significantly reduced the risk of clinically important upper gastrointestinal bleeding in critically ill patients undergoing invasive mechanical ventilation, with no significant effect on mortality. Secondary outcomes such as ventilator-associated pneumonia and C. difficile infection were similar between groups, but pantoprazole was associated with a reduction in patient-important bleeding.