Carbetocin vs. Oxytocin at Elective Cesarean Section: a Double-blind, Randomized Controlled Non-inferiority Trial of High and Low Dose Regimens

Postpartum hemorrhage (PPH) is a major cause of maternal death worldwide. Oxytocin is the most commonly used uterotonic drug to prevent and treat PPH in the world. However, oxytocin has a very short duration of action, requiring a continuous infusion to achieve sustained uterotonic activity. Moreover, large doses are associated with adverse effects like hypotension, nausea, vomiting, dysrhythmias and ST changes. The Society of Obstetricians and Gynecologists of Canada (SOGC) has recommended a single dose of 100 mcg of the longer acting carbetocin at elective cesarean section to promote uterine contraction. In multiple studies performed at Mount Sinai Hospital, we have shown that smaller doses of oxytocin (ED 90 0.35 IU) and carbetocin (ED 90 14.8 mcg) are effective in achieving adequate uterine tone at elective cesarean section. No study has directly compared the high dose regimens with the low dose regimens; therefore a large double-blind randomized controlled trial is necessary to show the non-inferiority of the lower doses of both drugs.

There is a lack of consensus as to what the optimal uterotonic regime is globally. Furthermore, variability in the international guidelines regarding the choice of first line uterotonic in prevention of PPH adds to the confusion. With the widespread availability of carbetocin in some of the developed countries, including Canada, the question of which uterotonic to adopt and at which dose becomes even more difficult to ascertain. Studies that have currently been published suggest the ED90 doses of carbetocin and oxytocin provide adequate uterine contraction with possibly fewer side effects associated with the lower dosed regimens. These advantages may provide a better safety profile and patient satisfaction. To the best of our knowledge, no studies have compared the low doses (ED90) of oxytocin vs. carbetocin, or low (ED90) vs high (conventional) doses of the two drugs in the setting of elective cesarean section. The results of this study will provide evidence on the efficacy and safety of the ED90 dosing compared directly to the higher dosing of both drugs.

Our hypothesis is that the ED90 doses of carbetocin and oxytocin will not be inferior to the higher dosing as determined by the intensity of uterine contraction using a VNRS in women undergoing elective cesarean section. We anticipate that the intensity of uterine contraction using the VNRS at 2 minutes post administration of all drugs will fall within the predetermined margin to signify non-inferiority of all regimens.