PEPTIC: A cluster randomised, crossover, registry-embedded clinical trial of proton pump inhibitors vs. histamine-2 receptor blockers for ulcer prophylaxis therapy in the Intensive Care Unit
Background
Around 2.5% of adults acutely admitted to an intensive care unit (ICU) develop upper gastrointestinal (GI) bleeding. To try to prevent this proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) – two commonly used drugs – are often prescribed. This is known as stress ulcer prophylaxis. Whether one of these drugs is better than the other for treating patients in ICU in terms of mortality is unknown. This is why we conducted the PEPTIC study to compare in-hospital mortality rates when using PPIs vs. H2RBs for stress ulcer prophylaxis.
Design
PEPTIC was a randomised, open-label, cluster crossover, registry-embedded trial, set in 50 ICU’s in 5 countries. In this cluster crossover trial, ICU’s were randomised to use one of two approaches to stress ulcer prophylaxis in mechanically ventilated adults. One approach was using PPIs as their first choice when stress ulcer prophylaxis was prescribed and the other was using H2RBs. By random allocation, each ICU used one approach for six months and then the alternative approach for the subsequent six months.
Results
A total of 26,982 patients were included in the trial. There was no significant difference in in-hospital survival between the two groups of patients with 18.3% of patients in the PPI group and 17.5% in the H2RB group dying in hospital by day 90 (risk ratio;1.05 95%CI,1.00-1.10;P=0.05). Clinically important upper GI bleeding was lower in patients in the PPI group, occurring in 1.3% of patients compared with 1.8% of patients in the H2RB (risk ratio;0.73 95%CI,0.57-0.92;P=0.009). Rates of Clostridioides difficile (bacteria)infection were 0.30% and 0.43% respectively (risk ratio;0.74 95%CI, 0.51-1.09;P=0.13). ICU and hospital length of stay were similar by treatment group.
Conclusion
The estimated effect on in-hospital mortality of using PPIs rather than H2RBs for stress ulcer prophylaxis in mechanically ventilated ICU patients ranges between no difference and a 10% relative increase. Preferentially using PPIs rather than H2RBs reduces clinically significant upper GI bleeding, but does not alter rates of Clostridioides difficile infection, ICU length of stay, or duration of hospitalization.
Who led the study?
Dr Stephen Wright Consultant in Anaesthesia and Intensive Care The Newcastle upon Tyne Hospitals NHS Foundation Trust
The study was funded by the Health Research Council of New Zealand, Irish Medical Council
Publications
Australian PIft, New Zealand Intensive Care Society Clinical Trials Group AHSCCSCN, the Irish Critical Care Trials G, Young PJ, Bagshaw SM, Forbes AB, Nichol AD, Wright SE, Bailey M, Bellomo R, Beasley R, Brickell K, Eastwood GM, Gattas DJ, van Haren F, Litton E, Mackle DM, McArthur CJ, McGuinness SP, Mouncey PR, Navarra L, Opgenorth D, Pilcher D, Saxena MK, Webb SA, Wiley D, Rowan KM. 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; :10.1001/jama.2019.22190. http://dx.doi.org/10.1001/jama.2019.22190
Young PJ, Bagshaw SM, Forbes A, Nichol A, Wright SE, Bellomo R, Bailey MJ, Beasley RW, Eastwood GM, Festa M, Gattas D, van Haren F, Litton E, Mouncey PR, Navarra L, Pilcher D, Mackle DM, McArthur CJ, McGuinness SP, Saxena MK, Webb S, Rowan KM. A cluster randomised, crossover, registry-embedded clinical trial of proton pump inhibitors versus histamine-2 receptor blockers for ulcer prophylaxis therapy in the intensive care unit (PEPTIC study): study protocol. Crit Care Resusc 2018; 20(3):182-9.