In-hospital mortality rates among patients requiring mechanical ventilation were not significantly different when comparing 2 stress ulcer prophylaxis strategies (proton pump inhibitors [PPIs] vs histamine-2 receptor blockers [H2RBs]), according to results of the PEPTIC (Proton Pump Inhibitors vs Histamine-2 Receptor Blockers for Ulcer Prophylaxis Treatment in the Intensive Care Unit) trial, published in JAMA.

The PEPTIC trial was a multicenter, cluster randomized, crossover, registry trial comparing the safety and efficacy of PPIs against H2RBs for stress ulcer prophylaxis in patients requiring invasive mechanical intervention within 24 hours of admission to the intensive care unit (ICU).

Patients were enrolled at 50 ICUs from August 2016 to January 2019 and had 90 days of in-hospital follow-up. Each ICU used each strategy for 6 months: 25 ICUs used PPIs first and H2RBs second, and 25 ICUs used H2RBs first and PPIs second. The primary outcome was all-cause, in-hospital mortality within 90 days. Secondary outcomes included upper gastrointestinal bleeding, Clostridioides difficile infection, and lengths of stay (ICU and hospital).

A total of 26,828 patients (men/women, 63.9%/36.1%) were included in the study (154 opted out). The average age was 58 years (standard deviation, 17.0 years). The mortality analysis included most patients (99.2%).

Of the patients assigned to initial PPI and H2RB groups, 18.3% (2459/13,415) and 17.5% (2333/13,356) died in the hospital within 90 days (risk ratio [RR], 1.05; 95% CI: 1.00-1.10; absolute risk difference, 0.93 percentage points; 95% CI, −0.01 to -1.88 percentage points; P =.054).

However, treating physicians had the option to override a patient’s treatment assignment after being randomly assigned, and to administer the nonpreferred strategy instead. An estimated 4.1% and 20.1% of patients assigned to receive PPIs and H2RBs received the nonpreferred strategy, H2RBs and PPIs, respectively, instead.

For the secondary outcomes, clinically important upper gastrointestinal bleeding occurred in fewer patients in the PPI group than in the H2RB group (1.3% vs 1.8%; RR, 0.73 [95% CI, 0.57-0.92]; absolute risk difference, −0.51 percentage points [95% CI, −0.90 to −0.12 percentage points]; P =.009). No significant differences were observed in C difficile infection rate or ICU and hospital lengths of stay.

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The study had several limitations. There was uncertainty about the site (upper or lower) and status of gastrointestinal bleeding, and some patients may have been bleeding before treatment. The mortality data may have errors because they were collected from registries. Physicians were allowed to choose which specific PPI or H2RB to administer and the route of administration. The nonadherence to assigned treatment strategy was asymmetric, with fewer physicians switching patients from PPIs to H2RBs than from H2RBs, indicating systematic reasons for switching.

“The findings from this study are broadly generalizable because enrolled patients were from 50 ICUs in 5 countries,” the authors concluded. “However, it is possible that a trial using different combinations of drugs or different routes of administration would have yielded different findings.”

Reference

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 [published online January 17,2020]. JAMA. doi:10.1001/jama.2019.22190