Carbetocin at Elective Cesarean Delivery Part 3

Study Overview
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Brief Summary
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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
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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.

Official Title
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Carbetocin at Elective Cesarean Deliveries: A Dose-finding Study Part 3

Conditions
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Postpartum Hemorrhage

Intervention / Treatment
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* Drug: Carbetocin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Carbetocin 100mcg<br>Carbetocin 100mcg, once following delivery of the fetal head. | Drug: Carbetocin<br>* Carbetocin IV, over 1 minute following delivery of the fetal head. Doses: 2, 5, 10, 15, 20 or 100mcg<br>* Other names: Duratocin;|
| Active Comparator: Carbetocin 20mcg<br>Carbetocin 20mcg, once following delivery of the fetal head. | Drug: Carbetocin<br>* Carbetocin IV, over 1 minute following delivery of the fetal head. Doses: 2, 5, 10, 15, 20 or 100mcg<br>* Other names: Duratocin;|
| Active Comparator: Carbetocin 15mcg<br>Carbetocin 15mcg, once following delivery of the fetal head. | Drug: Carbetocin<br>* Carbetocin IV, over 1 minute following delivery of the fetal head. Doses: 2, 5, 10, 15, 20 or 100mcg<br>* Other names: Duratocin;|
| Active Comparator: Carbetocin 10mcg<br>Carbetocin 10mcg, following delivery of the fetal head. | Drug: Carbetocin<br>* Carbetocin IV, over 1 minute following delivery of the fetal head. Doses: 2, 5, 10, 15, 20 or 100mcg<br>* Other names: Duratocin;|
| Active Comparator: Carbetocin 5mcg<br>Carbetocin 5mcg, following delivery of the fetal head. | Drug: Carbetocin<br>* Carbetocin IV, over 1 minute following delivery of the fetal head. Doses: 2, 5, 10, 15, 20 or 100mcg<br>* Other names: Duratocin;|
| Active Comparator: Carbetocin 2mcg<br>Carbetocin 2mcg, following delivery of the fetal head. | Drug: Carbetocin<br>* Carbetocin IV, over 1 minute following delivery of the fetal head. Doses: 2, 5, 10, 15, 20 or 100mcg<br>* Other names: Duratocin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uterine tone | The obstetrician will assess uterine tone by palpation. Uterine tone will be rated as satisfactory (firm) or unsatisfactory (boggy). Unsatisfactory uterine tone will be treated with oxytocin as per the obstetrician. | 2 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uterine tone | Uterine tone will be assessed by palpation 2 hours post-delivery by the nurse/obstetrician in the recovery room. | 2 hours | 
| Blood loss | Blood loss will be calculated through the difference in hematocrit values assessed prior to and at the end of 48 hours after the cesarean section. | 48 hours | 
| Side effects | Any of the following will be noted up to 2 hours post delivery: systolic blood pressure < 80% of pre-delivery values, tachycardia > 30% pre-delivery levels, bradycardia < 30% pre-delivery levels, other dysrhythmias, nausea, vomiting, chest pain, shortness of breath, headache, flushing, others | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pregnancy, postpartum hemorrhage, Cesarean delivery, carbetocin