Carbetocin at Elective Cesarean Deliveries: A Dose-finding Study in Women With BMI ≥ 40kg/m2
Condition: Postpartum Hemorrhage
MeSH terms: Postpartum Hemorrhage; Hemorrhage
Study type: Interventional

Summary: 
      Postpartum hemorrhage (PPH) due to uterine atony is a major cause of maternal morbidity and
      mortality. Carbetocin is a uterotonic with a superior pharmacokinetic profile to oxytocin. In
      a study performed at Mount Sinai Hospital, the investigators have shown that smaller doses of
      carbetocin (14.8 mcg) are as effective in achieving adequate uterine tone at elective
      cesarean section compared to the current recommended dose of 100mcg. However, this study was
      limited to those women with a body mass index (BMI) of <40 kg/m2. Maternal obesity has been
      shown to increase the risks of hemorrhage secondary to uterine atony, therefore the
      investigators wish to perform a dose finding study to determine the ED90 of carbetocin at
      caesarean section in those women with a BMI>40.
    

Detailed description: 
      Postpartum hemorrhage (PPH) is one of the leading causes of death during childbirth and
      accounts for an estimated 140,000 deaths per year worldwide. The World Health Organization
      (WHO) recommends active management of the third stage of labor to prevent PPH, even in low
      risk patients. Prophylactic uterotonic drugs administered after delivery are the main element
      of active management of the third stage and have been demonstrated to reduce the incidence of
      PPH by up to 40%.

      Oxytocin is the most commonly used uterotonic in North America, however it has a very short
      duration of action and requires a continuous infusion to achieve sustained effect, with large
      doses associated with adverse effects like low blood pressure, nausea, vomiting, abnormal
      heart rhythms and changes on ECG. Carbetocin is a synthetic oxytocin analogue. It causes
      uterine contraction via the same mechanism as oxytocin. Its duration of action is 4 to 7
      times that of oxytocin due to an increased biological half-life in plasma and at the oxytocin
      receptors in the uterus. The Society of Obstetricians and Gynecologists of Canada (SOGC) has
      recommended a single dose of 100 mcg of carbetocin at elective cesarean delivery to promote
      uterine contraction. In a study performed at Mount Sinai Hospital, the investigators have
      shown that smaller doses of carbetocin (14.8 mcg) are effective in achieving adequate uterine
      tone at elective cesarean section. However this study was limited to those women with a BMI
      of <40 kg/m2

      The prevalence of obesity is increasing in young women and some studies have shown that obese
      women have higher rates of caesarean delivery compared to non-obese women. Other studies have
      demonstrated an increased risk of hemorrhage due to poor uterine tone in obese women.
      Laboratory studies show that BMI alone appears to contribute to blunted uterine muscle
      responses and therefore contraction responses to oxytocin in obese women. Previous dose
      finding studies have excluded those women with a BMI of ≥40kgm2. Therefore, the investigators
      wish to perform a double-blind dose finding study using the biased coin up-and-down
      sequential allocation technique to determine the ED90 of carbetocin at caesarean section in
      those women with a BMI>40.
    

Intervention name(s): Carbetocin
Intervention type(s): Drug
Intervention description(s): carbetocin administered IV, over 1 minute following delivery of the fetal head
Other intervention name(s): Duratocin
Intervention MeSH terms: Carbetocin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Biased coin up-and-down design.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: pregnancy; postpartum hemorrhage; Cesarean delivery; carbetocin