Clinical trial NCT04902729: Oxytocin vs Carbetocin at Cesarean Delivery in Women With Morbid Obesity
Official title: Oxytocin Vs Carbetocin at Cesarean Delivery in Women With Morbid Obesity: Double-blind, Randomised Control, Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post Partum Hemorrhage
Keywords: pregnancy
postpartum hemorrhage
cesarean delivery
carbetocin
duratocin
oxytocin
Lead sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Sponsor class: OTHER
First posted: 2021-05-26
Enrollment: 48
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Uterine Tone 3 minutes
timeFrame: 3 minutes
Secondary outcomes:
measure: Uterine Tone 5 minutes
timeFrame: 5 min
measure: Uterine Tone 10 minutes
timeFrame: 10 min
measure: Additional uterotonics - operating room
timeFrame: 1-2 hours, length of surgery will vary
measure: Additional uterotonics - Post Anesthesia Care Unit (PACU)
timeFrame: 4 hours
measure: Additional uterotonics - 24 hours
timeFrame: 24 hours
measure: Estimated blood loss calculated
timeFrame: 24 hours
measure: Estimated blood loss, visual estimate provided by the obstetrician
timeFrame: 2 hours
measure: Hypotension: systolic blood pressure less than 80% of baseline
timeFrame: 2 hours
measure: Hypertension: systolic blood pressure greater than 120% of baseline
timeFrame: 2 hours
measure: Tachycardia: heart rate greater than 130% of baseline
timeFrame: 2 hours
measure: Bradycardia: heart rate less than 70% of baseline
timeFrame: 2 hours
measure: Presence of ventricular tachycardia: ECG
timeFrame: 2 hours
measure: Presence of atrial fibrillation: ECG
timeFrame: 2 hours
measure: Presence of atrial flutter: ECG
timeFrame: 2 hours
measure: Presence of nausea: questionnaire
timeFrame: 2 hours
measure: Presence of vomiting: questionnaire
timeFrame: 2 hours
measure: Presence of chest pain: questionnaire
timeFrame: 2 hours
measure: Presence of shortness of breath: questionnaire
timeFrame: 2 hours
measure: Presence of headache: questionnaire
timeFrame: 2 hours
measure: Presence of flushing: questionnaire
timeFrame: 2 hours
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Mrinalini Balki, MD
role: PRINCIPAL_INVESTIGATOR
References: