Clinical trial NCT01651130: Carbetocin at Elective Cesarean Delivery Part 3
Official title: Carbetocin at Elective Cesarean Deliveries: A Dose-finding Study Part 3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postpartum Hemorrhage
Keywords: pregnancy
postpartum hemorrhage
Cesarean delivery
carbetocin
Lead sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Sponsor class: OTHER
First posted: 2012-07-26
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Post-partum hemorrhage (PPH) is a major cause of maternal death worldwide. Oxytocin is the most common uterotonic drug used to prevent and treat PPH in North America, however, there are some limitations to its use. Oxytocin has a very short duration of action, which requires a continuous infusion to achieve sustained uterotonic activity. The Society of Obstetricians and Gynecologists of Canada (SOGC) has recently recommended a single 100mcg dose of carbetocin at elective Cesarean delivery to promote uterine contraction and prevent post partum hemorrhage (PPH), in lieu of the more traditional oxytocin regimens. Carbetocin lasts 4 to 7 times longer than oxytocin, with a similar side effect profile and apparent greater efficacy rate. However, a dose response study to determine the minimum effective dose of carbetocin has not yet been published. The investigators hypothesize that the minimum effective dose (ED90) is at least 20mcgs (or perhaps below) in women undergoing elective Cesarean delivery.

Detailed description: The Society of Obstetricians and Gynecologists of Canada (SOGC) recently recommended a 100mcg intravenous bolus dose of carbetocin following Cesarean delivery.

Studies thus far show that carbetocin may be just as effective as oxytocin in promoting uterine contraction, with a similar side effect profile. In addition, patients receiving carbetocin may experience less blood loss, and require less additional uterotonics when compared with oxytocin. Two dose response studies conducted at our institution (by Cordovani et al, and Anandakrishnan et al) suggested no difference in efficacy of uterine contraction for doses of carbetocin between 20-120mcg. Hypotension was noted for all dose groups studied.

This study will be conducted as a prospective, randomized, up-down sequential allocation trial. The success or fail of a patient in the study will determine the dose given to future patients. Dosage will be increased for patients following a failed case, and kept the same for patients following successful cases. Following a successful case, there is also a 1 in 9 chance that the dose will be decreased for the next patient.

The results of this follow-up study will define the minimum required dose of carbetocin for uterine contraction, thus minimizing unnecessary side effects, improving quality and safety of patient care. It may also contribute in establishing carbetocin as a substitute to oxytocin for elective cesarean section at our institution as well as others.

Eligibility criteria: Inclusion Criteria:

* Patients planned for elective cesarean delivery under spinal anesthesia
* Patients who give written informed consent to participate

Exclusion Criteria:

* Patients who refuse to give written informed consent
* Patients who claim allergy or hypersensitivity to carbetocin or oxytocin
* Patients with conditions that predispose to uterine atony and postpartum hemorrhage such as placenta previa, multiple gestation, preeclampsia, eclampsia, macrosomia, polyhydramnios, uterine fibroids, previous history of uterine atony and postpartum bleeding, or bleeding diathesis.
* Patients with hepatic, renal, and vascular disease
* Patients requiring general anesthesia prior to the administration of the study drug.

Primary outcomes:
measure: Uterine tone
timeFrame: 2 minutes
Secondary outcomes:
measure: Uterine tone
timeFrame: 2 hours
measure: Blood loss
timeFrame: 48 hours
measure: Side effects
timeFrame: 2 hours
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Jose CA Carvalho, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Khan M, Balki M, Ahmed I, Farine D, Seaward G, Carvalho JC. Carbetocin at elective Cesarean delivery: a sequential allocation trial to determine the minimum effective dose. Can J Anaesth. 2014 Mar;61(3):242-8. doi: 10.1007/s12630-013-0082-9. Epub 2013 Nov 27.