GI prophylaxis for the critically ill: PEPTIC gives commentator ulcers

  • Young PJ & al.
  • JAMA
  • 17 ene. 2020

  • de Jenny Blair, MD
  • Clinical Essentials
El acceso al contenido completo es sólo para profesionales sanitarios registrados. El acceso al contenido completo es sólo para profesionales sanitarios registrados.


  • For critically ill patients, proton pump inhibitors (PPIs) and histamine-2 receptor blockers (H2RBs) were associated with similar mortality rates when prescribed to prevent stress ulcers.
  • Editorial discusses limitations relating to: 
    • High crossover rates.
    • Cluster-level data limited on, e.g., infections.
    • Possible mortality signal lacks clear mechanism.

Why this matters

  • Safety of PPIs vs H2RBs for critically ill has been unclear.
  • PPIs have been linked to important harms. 

Key results

  • PPI vs H2RB: 
    • Mortality: 18.3% vs 17.5%; risk ratio (RR), 1.05 (95% CI, 1.00-1.10; P=.054).
    • Clinically important upper gastrointestinal bleeding: 1.3% vs 1.8%; RR, 0.73 (95% CI, 0.57-0.92).
    • Similar rates of Clostridioides difficile infection; ICU, hospital lengths of stay.

Study design

  • International pragmatic randomized open-label registry-embedded cluster crossover PEPTIC trial (n=26,828).
  • For critically ill patients receiving mechanical ventilation, 50 ICUs were randomly assigned to give PPI vs H2RB for gastrointestinal prophylaxis.
  • After 6 months, ICUs switched to other drug.
  • Clinicians could override randomization, switch patients to other drug.
  • Outcome: 90-day in-hospital mortality.
  • Funding: Commonwealth governments and/or nonprofits. 


  • Crossover rates: 
    • H2RB-to-PPI: 20.1%.
    • PPI-to-H2RB: 4.1%.
  • Potential indication bias “might have masked higher mortality from [PPIs] and attenuated the benefit of a [PPI] strategy on clinically important upper gastrointestinal bleeding,” editor argues.