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 | Critical Care Medicine | JAMA | JAMA Network
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A 2020 cluster randomized trial found no difference in in-hospital mortality among nearly 27,000 mechanically patients assigned to an intensive care unit (ICU)-level strategy of stress ulcer prophylaxis with proton pump inhibitors (PPIs) vs histamine-2 receptor blockers (H2RBs). Paul J. Young, PhD, of Wellington Hospital in New Zealand, presented findings from the PEPTIC Trial at the Critical Care Reviews 2020 meeting (CCR20), on January 17 in Belfast, Northern Ireland. An oral editorial and Q&A session follows. Click the related article link for full trial details. Video used with permission.

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Original Investigation
Caring for the Critically Ill Patient
January 17, 2020

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

The PEPTIC Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Alberta Health Services Critical Care Strategic Clinical Network, and the Irish Critical Care Trials Group
JAMA. 2020;323(7):616-626. doi:10.1001/jama.2019.22190
Key Points

Question  What is the comparative effect on in-hospital mortality of using proton pump inhibitors (PPIs) vs histamine-2 receptor blockers (H2RBs) for stress ulcer prophylaxis among adults requiring invasive mechanical ventilation in the intensive care unit (ICU)?

Findings  In this cluster crossover randomized clinical trial, 26 982 patients requiring invasive mechanical ventilation within 24 hours of ICU admission were randomized by site at 50 ICUs in 5 countries to a PPI strategy or an H2RB strategy for stress ulcer prophylaxis. In-hospital mortality was 18.3% for patients treated at sites randomized to PPI use vs 17.5% for those treated at sites randomized to H2RB use, a difference that did not reach statistical significance (P = .054). Among patients treated at sites randomized to PPIs, 4.1% received H2RBs; among patients treated at sites randomized to H2RBs, 20.1% received PPIs.

Meaning  A strategy of use with PPIs vs H2RBs for stress ulcer prophylaxis among adults requiring mechanical ventilation did not result in a statistically significant difference for in-hospital mortality, but study interpretation may be limited by crossover in medication use.

Abstract

Importance  Proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The comparative effect of these drugs on mortality is unknown.

Objective  To compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis.

Design, Setting, and Participants  Cluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital.

Interventions  Two stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H2RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H2RBs and 25 ICUs were randomized to the sequence with use of H2RBs and then use of PPIs (13 436 patients randomized by site to PPIs and 13 392 randomized by site to H2RBs).

Main Outcomes and Measures  The primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay.

Results  Among 26 982 patients who were randomized, 154 opted out, and 26 828 were analyzed (mean [SD] age, 58 [17.0] years; 9691 [36.1%] were women). There were 26 771 patients (99.2%) included in the mortality analysis; 2459 of 13 415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2333 of 13 356 patients (17.5%) in the H2RB group died at the hospital by day 90 (risk ratio, 1.05 [95% CI, 1.00 to 1.10]; absolute risk difference, 0.93 percentage points [95% CI, −0.01 to 1.88] percentage points; P = .054). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H2RBs and an estimated 20.1% of patients randomized by ICU site to H2RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H2RB group (risk ratio, 0.73 [95% CI, 0.57 to 0.92]; absolute risk difference, −0.51 percentage points [95% CI, −0.90 to −0.12 percentage points]; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group.

Conclusions and Relevance  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.

Trial Registration  anzctr.org.au Identifier: ACTRN12616000481471

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