WHO Study on Carbetocin and Oxytocin for Postpartum Bleeding

Introduction to Postpartum Bleeding

The World Health Organization (WHO) partnered with Merck, Sharpe & Dohme to investigate the efficacy of carbetocin compared to oxytocin in reducing postpartum bleeding after vaginal deliveries. Postpartum hemorrhage remains a leading cause of maternal mortality globally, with approximately 661,000 deaths reported from 2001 to 2009. Over 70% of these deaths result from bleeding, primarily due to inadequate uterine contraction following childbirth.

Challenges with Oxytocin Storage

The WHO endorses oxytocin as the preferred medication to prevent excessive bleeding post-delivery. However, its requirement for storage and transport at temperatures between 2-8°C poses significant challenges, especially in low and middle-income countries. In these regions, access to this critical drug is often limited, and exposure to higher temperatures can diminish oxytocin’s effectiveness.

Advantages of Carbetocin

Carbetocin, an analog of oxytocin, offers a potential solution as it is stable and does not necessitate cold chain storage or transport. Research indicates that carbetocin maintains its stability for up to 36 months at temperatures of 30°C and 75% relative humidity.

Research Study Overview

A recent study conducted by WHO researchers in collaboration with Merck & Co. aimed to evaluate the effectiveness of carbetocin in preventing postpartum bleeding and subsequently reducing maternal mortality. The findings were published in The New England Journal of Medicine. The study involved 29,645 women from around ten countries, all of whom had undergone vaginal births. Participants were randomly assigned to receive either carbetocin or oxytocin immediately after delivery. To preserve the integrity of the study, both medications were stored at controlled temperatures.

Study Results

The study’s outcomes revealed that both carbetocin and oxytocin were similarly effective in preventing blood loss of at least 500 mL or the need for additional uterotonic agents. Specifically, the incidence of blood loss among women receiving carbetocin was 14.5%, compared to 14.4% in those given oxytocin. Carbetocin demonstrated non-inferiority to oxytocin in preventing blood loss of at least 500 mL; however, it did not show similar results for blood loss of at least 1000 mL, with frequencies of 1.51% and 1.45%, respectively.

Conclusion

The study concluded that heat-stable carbetocin is as effective as oxytocin for preventing excessive postpartum bleeding following vaginal delivery. This finding underscores the potential benefits of carbetocin in low and middle-income countries, where oxytocin may be compromised due to temperature sensitivity.

References

Widmer M, Piaggio G, Nguyen TMH, Osoti A, Owa OO, Misra S, Coomarasamy A, Abdel-Aleem H, Mallapur AA, Qureshi Z, Lumbiganon P, Patel AB, Carroli G, Fawole B, Goudar SS, Pujar YV, Neilson J, Hofmeyr GJ, Su LL, Ferreira de Carvalho J, Pandey U, Mugerwa K, Shiragur SS, Byamugisha J, Giordano D, Gülmezoglu AM; WHO CHAMPION Trial Group. Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth. N Engl J Med. 2018. Torjesen I. Alternative drug to prevent postpartum bleeding could save many lives in low-income countries. BMJ. 2018;361:k2859.