Ulcer Prophylaxis

Proton pump inhibitors (PPIs) are among the most widely prescribed drugs in the intensive care unit (ICU). Many, if not most, prescriptions of PPIs in the ICU are for stress ulcer prophylaxis. Although PPIs are used most widely for this indication, histamine-2 receptor blockers (H2RBs) are used in preference to PPIs in some ICUs. This variation, which appears to be largely dependent on clinician preference rather than patient-specific factors, has continued for decades.

A landmark trial of unprecedented size and statistical power, the PEPTIC Study, is the largest randomised clinical trial ever undertaken in the field of intensive care medicine, gathering findings from almost 27,000 patients from 50 ICUs in five countries.

The PEPTIC study, led by the MRINZ Intensive Care team, compared the risk of death with the two ulcer-preventing medicines commonly prescribed to critically ill patients in the ICU. This was the first study adequately powered to determine whether or not the choice of stress ulcer prophylaxis in the ICU affects the risks of mortality and of developing important complications such as ulcer bleeding and hospitalacquired infections.

The study used the innovative approach of collecting outcome data from existing databases, allowing the research team to complete a high quality, prospective interventional trial at a very low cost. The study showed that while PPIs are slightly better at preventing bleeding from ulcers, they increased the risk of dying in hospital compared with the alternative H2RB blockers. In 2021, this study was awarded the ACTA STInG Excellence in Statistics Award and was a Trial of the Year Finalist in recognition of the impact of the findings to change practice and improve outcomes internationally.

When we began this landmark vitamin C trial, we were caught between two groups — strong proponents of the potential therapy and those who felt that it lacked evidence and ought to be abandoned. With such contrary views, we appreciated the importance of further study. Our collaboration with MRINZ researchers serves as an example of the importance of challenging dogma through a multinational effort and embedding research in clinical care. Treatments administered to our patients should be examined in high-quality trials.