Oxytocin vs Carbetocin at Cesarean Delivery in Women With Morbid Obesity

Study Overview
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Brief Summary
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Postpartum hemorrhage (PPH) is a major cause of maternal death worldwide. Oxytocin is the most commonly used uterotonic drug for the active management of third stage labor, to reduce the risk of PPH and help deliver the placenta. Carbetocin is currently recommended by the SOGC (Society of Obstetricans & Gynecologists of Canada), and is a relatively newer drug with a longer duration of action. It has been previously demonstrated that women with elevated BMI require higher doses of these drugs to induce adequate uterine contraction and dose finding studies undertaken at Mount Sinai Hospital have shown that the ED 90 in obese patients to be carbetocin 80 mcg and oxytocin 1IU. Furthermore, previous studies have indicated that the use of carbetocin over oxytocin in non-obese popultion is associated with reduced bleeding and requirement of additional uterotonic medications. No study has directly compared the two drugs in obese parturients in a head to head clinical trial; therefore a double-blind randomized controlled trial is necessary to show the non-inferiority of carbetocin against the current standard of care at Mount Sinai hospital, which is oxytocin.

Detailed Description
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Obesity in pregnancy is defined as a Body Mass Index (BMI) above 30 kg/m2 and is often cited as a risk factor for PPH after cesarean delivery. The World Health organization (WHO) recommends that uterotonic medications are routinely administered at cesarean delivery for the active management of the third stage of labor, both to facilitate delivery of the placenta and to reduce the risk of PPH. The optimal regimen for active management of third stage of labor is yet to be fully determined and obesity adds another layer of complexity and risk, with higher doses required to induce adequate uterine contraction. While oxytocin is the most commonly used drug world-wide, multiple agents are available and there is no clear consensus as to which drug should be first choice. Multiple studies have shown that carbetocin is associated with reduced post-partum bleeding, need for blood transfusion and additional uterotonic medications, in the non-obese population. The results of this study will provide evidence on the non-inferiority of carbetocin when compared directly to the current standard of care at Mount Sinai hospital, which is oxytocin. The investigators hypothesize that when administered in equipotent doses, carbetocin would be non-inferior to oxytocin in women with BMI ≥40 kg/m2 undergoing elective cesarean delivery. The investigators hope to prove that the difference between uterine tone elicited by carbetocin falls within the inferiority margin of -1.2 using a verbal numerical rating score.

Official Title
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Oxytocin Vs Carbetocin at Cesarean Delivery in Women With Morbid Obesity: Double-blind, Randomised Control, Non-inferiority Trial

Conditions
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Post Partum Hemorrhage

Intervention / Treatment
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* Drug: Carbetocin
* Drug: Oxytocin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI≥40 kg/m2 Elective cesarean delivery under spinal, epidural, or combined spinal-epidural anaesthesia Written informed consent Full term pregnancy (37+0 to 40+6 weeks gestation) Non-labouring patients Exclusion Criteria: Refusal to give written informed consent Allergy or hypersensitivity to carbetocin or oxytocin Laboring patients Need for general anaesthesia Conditions that predispose to uterine atony and postpartum haemorrhage including but not limited to: Placenta previa Multiple gestations Preeclampsia Eclampsia Polyhydramnios Uterine fibroids Previous history of uterine atony and postpartum bleeding Bleeding diathesis Hepatic, renal, and cardiovascular disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oxytocin 1IU<br>Oxytocin 1IU, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby, followed by infusion 80 mU/min (40 IU in 1L given at a rate of 120 mL/h). | Drug: Oxytocin<br>* Patient is given oxytocin (1IU) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby, followed by infusion 80 mU/min (40 IU in 1L given at a rate of 120 mL/h).<br>* Other names: Pitocin;|
| Active Comparator: Carbetocin 80mcg<br>Carbetocin 80mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby. | Drug: Carbetocin<br>* Patient is given carbetocin (80mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.<br>* Other names: Duratocin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uterine Tone 3 minutes | The primary outcome will be the intensity of uterine tone as evaluated by palpation of the uterus by the obstetrician at 3 minutes, from the completion of delivery of the drug, utilising a VNRS scale of 0-10. | 3 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uterine Tone 5 minutes | Intensity of uterine tone on a VNRS scale of 0-10 as evaluated by the obstetrician at 5 minutes after completion of injection of the bolus study drug. | 5 min | 
| Uterine Tone 10 minutes | Intensity of uterine tone on a VNRS scale of 0-10 as evaluated by the obstetrician at 10 minutes after completion of injection of the bolus study drug. | 10 min | 
| Additional uterotonics - operating room | The use of additional uterotonic agents in the operating room | 1-2 hours, length of surgery will vary | 
| Additional uterotonics - Post Anesthesia Care Unit (PACU) | The use of additional uterotonic agents at any time after admission to the recovery area (Post Anesthesia Care Unit (PACU)) until transfer to the post partum ward. | 4 hours | 
| Additional uterotonics - 24 hours | The use of additional uterotonic agents at any time after discharge from the recovery area (Post Anesthesia Care Unit (PACU)) and up to 24 hours post delivery | 24 hours | 
| Estimated blood loss calculated | Blood loss will be calculated through the difference in hematocrit values assessed prior to and at the end of 24 hours after the cesarean section. | 24 hours | 
| Estimated blood loss, visual estimate provided by the obstetrician | Blood loss in ml, as reported by the obstetrician at the end of the surgery. | 2 hours | 
| Hypotension: systolic blood pressure less than 80% of baseline | Systolic blood pressure < 80% of baseline, from drug administration until end of surgery | 2 hours | 
| Hypertension: systolic blood pressure greater than 120% of baseline | Systolic blood pressure > 120% of baseline, from drug administration until end of surgery | 2 hours | 
| Tachycardia: heart rate greater than 130% of baseline | Heart rate > 130% of baseline, from drug administration until end of surgery | 2 hours | 
| Bradycardia: heart rate less than 70% of baseline | Heart rate < 70% of baseline, from drug administration until end of surgery | 2 hours | 
| Presence of ventricular tachycardia: ECG | Presence of ventricular tachycardia as recorded by ECG, from drug administration until end of surgery | 2 hours | 
| Presence of atrial fibrillation: ECG | Presence of atrial fibrillation as recorded by ECG, from drug administration until end of surgery | 2 hours | 
| Presence of atrial flutter: ECG | Presence of atrial flutter as recorded by ECG, from drug administration until end of surgery | 2 hours | 
| Presence of nausea: questionnaire | The presence of nausea and number of episodes, from drug administration until end of surgery, as reported by the patient | 2 hours | 
| Presence of vomiting: questionnaire | The presence of vomiting and number of episodes, from drug administration until end of surgery | 2 hours | 
| Presence of chest pain: questionnaire | Any presence of chest pain, from drug administration until end of surgery, as reported by the patient | 2 hours | 
| Presence of shortness of breath: questionnaire | Any presence of shortness of breath, from drug administration until end of surgery, as reported by the patient | 2 hours | 
| Presence of headache: questionnaire | Any presence of headache, from drug administration until end of surgery, as reported by the patient | 2 hours | 
| Presence of flushing: questionnaire | Any presence of flushing, from drug administration until end of surgery | 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, duratocin, oxytocin