Kart, M. Pantoprazole in patients at risk for Gastrointestinal Bleeding in the ICU. N Engl J Med 2018;379:2199-208.
Trial done in the UK. It was a multicenter, stratified, parallel group, placebo controlled blinded randomized trial.
Included pts admitted to the ICU who were 18 yo or older and had at least one risk of actor for clinically important GIB including, shock, anticoagulants, crrt, MV >24hours, any liver disease, he of or ongoing coaulopathy
Primary outcome was death by 90 days after randomization. Secondary outcomes were GI bleeding, new onset pna, c. Diff. Predefined subgroups including SAPS II of >53 and <53
Pts were randomized to receive either 40mg IV pantoprazole daily until ICU discharge for a maximum of 90 days
- For the primary outcome of mortality 31.1% vs 30.4% died (RR 1.02; 0.91-1.13, p=0.76)
- For the outcome of clinically important GIB 2.5% of pantop group vs 4.2% of placebo had clinically important GIB.
- The RR of have a SAPSII >53 was 1.13 (0.99-1.30) vs 0.92 (0.78-1.09) p=0.05.
- This was the subgroup with the largest separation of average RR (Despite overlapping C.I. and both crossed 1 when compared to other subgroups of shock, vent, etc.
The study was powered to detect a 5% difference which seems really large and unlikely. To power a less then 1% difference would take a vastly larger trial. The endpoint of clinically important GIB seems like that should have been the primary outcome. Since it is only hypothesis generating we cant say much about it. Taken at face value there is probably a group that would benefit more than the ones they picked. Maybe they should have enrolled ICU pts with SAPSII >53 as one of the inclusion criteria to see if there would be a bigger impact. However, this is a large trial with around 3300 pts so getting this done again will be unlikely. Probably sick ICU pts should get SUP for the prevention of GIB but not death and consider maybe a sicker population because right now the NNT for prevention of GIB is around 60.
Last not there were a lot of these docs getting monies from drug companies…