Study Design Summary: Multicenter, placebo controlled trial of adults with postpartum hemorrhage in either vaginal or cesarian section delivery with initial primary end point as composite outcome of death and need for hysterectomy, but due to well explained reasons they analyzed death secondary to bleeding as well which seems a better endpoint.
Notes: The TXA and placebo groups were identical interns of average age, type of delivery, time from delivery to randomization, primary cause of hemorrhage, blood pressure, signs of hemodynamic instability and EBL.
FOAM points: SGEM:The study was funded in part by Pfizer the maker of TXA. This should make us more skeptical of the results and how the results will be marketed by the sponsor. REBELEM: All cause mortality was unchanged (2.3% vs 2.6%, p=0.16). The NNT was large (267) with a fragility index of 0.
There is some argument that disease specific mortality is a poor outcome because it can be hard to decipher what exactly patients died of and there can be large inter-evaluator reliability. There is also the argument that patients don’t care what they died of just if they died or not. I take issue with the second argument because I’m giving TXA to stop bleeding, not prevent sepsis.
The initial primary outcome was composite of death and hysterectomy but often patients were randomized to the trial and undergoing emergent hysterectomy at the same time thus prior to any results available to the study designers they changed primary outcome top death secondary to bleeding. I think this is likely a better outcome as it is simpler with less background noise.
Death due to bleeding in the TXA group vs placebo was 1.2% vs 1.7% (CI 0.53-0.90 favoring TXA with p=0.008) when given in the first three hours and 2.6% vs 2.5% (CI 0.76-1.51) when given after 3 hours. TXA in the first 3 hours also reduced number of laparotomies to control bleeding with statistically significant numbers. This is also an important outcome that is not discussed in many of the negative FOAM posts. Risk of thromboembolic events, both venous and arterial, were similar between the two groups.
I think the study does show positive results on the results that matter but I am skeptical to trust a study funded by the drug company.
Study Conclusion: TXA reduces mortality in patients with postpartum hemorrhage when given within the first 3 hours, without a significant increase in VTE; consistent with CRASH-2 trial results.
Fusion Beat Bottom Line Impression: TXA should be given to patients within 3 hours of delivery with postpartum hemorrhage to significantly reduce risk of death.
A Fusion Beat 