Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers
PEPTIC trial design and results
Design
Cluster-randomised crossover trial
Treatment
Proton pump inhibitor as the default prophylactic agent
Control
Histamine-2 receptor blocker as the default agent
Population
26,828 analysed ICU patients receiving invasive mechanical ventilation, mean age 58, 36.1% women
Follow-up
90 days
Primary endpoint
In-hospital mortality within 90 days
Result
In-hospital mortality by day 90 was 18.3% (2459 of 13,415) with a proton pump inhibitor and 17.5% (2333 of 13,356) with an H2 blocker — risk ratio 1.05 (95% CI 1.00 to 1.10), p=0.054. Clinically important upper gastrointestinal bleeding was lower with proton pump inhibitors, 1.3% versus 1.8% (risk ratio 0.73, 95% CI 0.57 to 0.92, p=0.009). Clostridioides difficile infection and lengths of stay did not differ. An estimated 20.1% of patients in H2-blocker units actually received a proton pump inhibitor.
Secondary endpoints
Clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, ICU length of stay
Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication.
The trial authors, in the published abstract
How it has aged
Enormous, pragmatic, and neutral on mortality — but not on everything. Proton pump inhibitors reduced the bleeding that prophylaxis is prescribed to prevent, while the mortality risk ratio of 1.05 had a confidence interval touching 1.00. Substantial crossover at unit level dilutes both signals. Whether prophylaxis is given at all was settled later by REVISE.
Publications
Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial
Young PJ, Bagshaw SM, Forbes AB, et al. Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial. JAMA 2020 Feb 18;323(7):616-626.