Widmer M, et al. - This trial was conducted to compare a novel formulation of heat-stable carbetocin to oxytocin in terms of prevention of postpartum hemorrhage after vaginal birth. According to findings, heat-stable carbetocin was noninferior to oxytocin as a preventive of blood loss of at least 500 ml or the use of additional uterotonic agents. Data showed that, noninferiority was not shown for the outcome of blood loss of at least 1000 ml.

Methods

• This is a randomized, double-blind, noninferiority trial, in which women were enrolled across 23 sites in 10 countries.
• Researchers compared intramuscular injections of heat-stable carbetocin (at a dose of 100 μg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth.
• Double-blinding was maintained by keeping both drugs in cold storage (2 to 8°C).
• The proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml were the primary outcomes.
• The noninferiority margins for the relative risks of these outcomes were 1.16 and 1.23, respectively.

Results

• Randomization involved 29,645 women.
• In the carbetocin group and in the oxytocin group, the observed frequency of blood loss of at least 500 ml or the use of additional uterotonic agents was 14.5% and 14.4%, respectively (relative risk, 1.01; 95% confidence interval [CI], 0.95 to 1.06), a finding that was consistent with noninferiority.
• Findings revealed that, 1.51% was the estimated frequency of blood loss of at least 1000 ml in the carbetocin group and 1.45% in the oxytocin group (relative risk, 1.04; 95% CI, 0.87 to 1.25), with the confidence interval crossing the margin of noninferiority.
• The two groups showed no significant difference in terms of use of additional uterotonic agents, interventions to stop bleeding, and adverse effects.