Carbetocin vs. Oxytocin at Elective Cesarean Section
Condition: Postpartum Hemorrhage
MeSH terms: Postpartum Hemorrhage; Hemorrhage
Study type: Interventional

Summary: 
      The study investigators are comparing 2 drugs (oxytocin and carbetocin) at 2 different
      dosages, to help prevent serious bleeding (hemorrhage) after cesarean deliveries. These drugs
      are used routinely to help contract the uterus and keep it contracted after the delivery of
      the baby and placenta; this reduces the amount of blood you might lose. At Mount Sinai
      Hospital, currently oxytocin is used, but its effect on the uterus is much shorter than that
      of carbetocin. Internationally, there is no consensus as to what the most effective drug to
      use is and at which dose. The Society of Obstetricians and Gynaecologists of Canada has
      recently revised its guidelines to suggest 100 micrograms (mcg) of carbetocin as the drug of
      choice at elective cesarean section. Guidelines from the United Kingdom and the United States
      currently suggest oxytocin at various doses as the drug of choice at elective cesarean
      sections. Previous studies at Mount Sinai Hospital have shown that lower doses of oxytocin,
      0.35 International Units (IU), and carbetocin, 20 mcg, may be as effective as the higher
      recommended doses. The investigators plan to conduct a large study to confirm these findings
      so that they can use the most appropriate dose in the future. Furthermore, the investigators
      hope to demonstrate that side effects are lower with the lower dose regimens.
    

Detailed description: 
      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.
    

Intervention name(s): Carbetocin; Oxytocin
Intervention type(s): Drug; Drug
Intervention description(s): Patient is given carbetocin (20 or 100 mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.; Patient is given oxytocin (0.5 or 5 IU) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Other intervention name(s): Duratocin; Pitocin
Intervention MeSH terms: Oxytocin; Carbetocin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: pregnancy; postpartum hemorrhage; cesarean delivery; carbetocin; duratocin; oxytocin