Carbetocin vs. oxytocin at elective caesarean delivery: a double-blind, randomised, controlled, non-inferiority trial of low- and high-dose regimens

Carbetocin or oxytocin are given routinely as first-line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage. Low doses may be as effective as high doses with a potential reduction in adverse effects. In this double-blind, randomised, controlled, non-inferiority trial, we assigned low-risk patients undergoing elective caesarean delivery under spinal anaesthesia to one of four groups: carbetocin 20 mu g; carbetocin 100 mu g; oxytocin 0.5 IU bolus + infusion; and oxytocin 5 IU bolus + infusion. The study drug was given intravenously after delivery of the neonate. Uterine tone was assessed by the obstetrician 2, 5 and 10 minutes after study drug administration according to an 11-point verbal numerical rating scale (0 = atonic, 10 = excellent tone). The primary outcome measure was uterine tone 2 min after study drug administration. The pre-specified non-inferiority margin was 1.2 points on the 11-point scale. Secondary outcomes included uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects. Data were available for 277 patients. Carbetocin 20 mu g resulting in uterine tone of (median (IQR [range])) 8 (7-8 [1-10]) was non-inferior to carbetocin 100 mu g with tone 8 (7-9 [3-10]), median (95%CI) difference 0 (-0.44-0.44). Similarly, oxytocin 0.5 IU with tone 7 (6-8 [3-10]) was non-inferior to oxytocin 5 IU with tone 8 (6-8 [2-10]), median (95%CI) difference 1 (0.11-1.89). Carbetocin 20 mu g was also non-inferior to oxytocin 5 IU, and oxytocin 0.5 IU was non-inferior to carbetocin 100 mu g. Uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects were similar in all groups.