Oxytocin vs Carbetocin at Cesarean Delivery in Women With Morbid Obesity

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

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.

Study Overview

• Status: Completed
• Conditions: Post Partum Hemorrhage
• Intervention / Treatment: Drug: Oxytocin; Drug: Carbetocin

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X5
      • Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxytocin 1IU; 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; 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).; Other Names: Pitocin
Active Comparator: Carbetocin 80mcg; Carbetocin 80mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.	Drug: Carbetocin; Patient is given carbetocin (80mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.; Other Names: Duratocin

What is the study measuring?

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
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
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
Bradycardia: heart rate less than 70% of baseline	Heart rate < 70% of baseline, from drug administration until end of surgery	2 hours
Presence of flushing: questionnaire	Any presence of flushing, from drug administration until end of surgery	2 hours
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

Collaborators and Investigators

• Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Actual): December 8, 2022
• Study Completion (Actual): December 9, 2022

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: May 21, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: oxytocin; pregnancy; postpartum hemorrhage; cesarean delivery; carbetocin; duratocin
• Additional Relevant MeSH Terms: Pathologic Processes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Obesity; Uterine Hemorrhage; Hemorrhage; Obesity, Morbid; Postpartum Hemorrhage; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin; Carbetocin
• Other Study ID Numbers: 21-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No