PEPTIC Study Dr Swapnil Pawar
This was a multi-centre cluster randomised trial involving 50 ICUs in Australia, New Zealand, Canada, Ireland, and the UK. The units were randomised (as opposed to individual patient randomization) to one type of stress ulcer prophylaxis for 6 months and then switched over to the other medication.
Included: The study population included adult patients 18 years and older who underwent invasive mechanical ventilation in the first 24 hours of ICU admission.
Not included: Patients who were admitted to the ICU with upper gastrointestinal bleeding
The PEPTIC trial was an open-label, unblinded trial. A proton pump inhibitor or a histamine-2 receptor blocker was administered according to the ICU randomization status among those who were deemed to require stress ulcer prophylaxis according to the treating clinician,. Regardless of assigned therapy, either treatment could be administered based on clinician judgement. The assigned treatment was continued until death, ICU discharge, presence of clinically important upper gastrointestinal bleed, or until stress ulcer prophylaxis was considered to be not indicated anymore. In case upper gastrointestinal bleed occurred, a proton pump inhibitor was administered at clinician discretion.
The investigators assumed an absolute reduction in hospital mortality (the primary outcome) of 2.4% from a baseline mortality of 15%; corresponding to a relative risk reduction 16%. This required a mean cluster period size of 310 patients. Sensitivity analyses was carried out for missing data in the following manner. In the worst-best scenario for a binary outcome like mortality, a worst outcome event (e.g., in-hospital death) was assigned to all patients with missing data for the outcome in one treatment group, and a best outcome event (in-hospital survival) was assigned to all patients with missing data for the outcome in the other treatment group. The best-worst scenario was carried out in the reverse manner.
26 828 patients enrolled à13 436 assigned to proton pump inhibitors à 13 392 to histamine-2 receptor blockers. After exclusion of patients who presented with upper GI bleed, those who opted out, and those with missing mortality data,
Patients were matched at baseline.
In-hospital, all-cause mortality during the index hospitalization on follow-up until 90 days from the date of the initial ICU admission. PPIs vs. H2-receptor antagonists:
2459/13 415 (18.3) vs. 2333/13 356 (17.5); RR, 1.05 (1.00 to 1.10); p = 0.054
Clinically important upper GI bleed PPIs vs. H2-receptor antagonists:
1.3 vs. 1.8%; RR, 0.73 (0.57 to 0.92); p = 0.009
Clostridium difficile infection PPIs vs. H2-receptor antagonists: 0.3 vs. 0.43%; RR, 0.74 (0.51 to 1.09); p = 0.13
ICU and hospital days among survivors: Not different
Hours on mechanical ventilation
Post-operative cardiac surgical patients: PPI vs histamine-2 receptor blocker group, the RR for the primary outcome: 1.27 (95% CI, 1.04-1.57)
Based on severity of illness according to the APACHE II score:
APACHE II score up to 17, no difference
APACHE II score range: 18-23: 17.5 vs.14.7%; RR: 1.15 (1.05-1.25)
APACHE II score range: 24-61: 45.3 vs. 43.5%; RR: 1.05 (1.00-1.11)
-Thought-provoking and the landmark trial
-Unable to change practices due to unavailability of suitable H2 receptor antagonists.
-Need large RCT comparing acid suppression therapy vs standard practices in ICU.