Postpartum haemorrhage (PPH) is the leading cause of maternal mortality
in low-income countries and contributes to nearly a quarter of maternal
deaths globally. The current available interventions for prevention of
postpartum haemorrhage, oxytocin and carbetocin, are limited by their
need for refrigeration to maintain potency, as the ability to maintain
cold-chain across the drug distribution and storage network is
inconsistent, thus restricting their use in countries with the highest
burden of maternal mortality.
The World Health Organization, Merck for Mothers and Ferring
Pharmaceuticals discussed room temperature stable carbetocin (carbetocin
RTS) as a promising intervention for reducing PPH, and agreed to proceed
with a randomized, double-blind, non-inferiority trial to evaluate the
effectiveness of carbetocin RTS compared to oxytocin for the prevention
of PPH after vaginal birth.
Approximately 30,000 women delivering vaginally will be recruited across
22 centers in 10 countries.
The primary objectives are to evaluate the non-inferiority of room
temperature stable carbetocin (100 μg intramuscular) versus oxytocin (10
IU intramuscular) in the prevention of PPH and severe PPH after vaginal
birth. The primary endpoints are blood loss ≥500 mL or the use of
additional uterotonics (composite endpoint), and blood loss ≥1000 mL.
If the results of the study show that carbetocin RTS is a safe and
effective alternative to oxytocin, this could have substantial impact on
the prevention of PPH and maternal survival worldwide. Should that be
the case, the WHO recommendations for the prevention and treatment of
PPH will be updated accordingly, HRP/RHR will undertake the application
to the WHO Model List of Essential Medicines and carbetocin RTS will be
made available in high-burden countries at a public sector price
comparable to oxytocin’s price.