Carbetocin at Elective Cesarean Deliveries: A Dose-finding Study in Women With Twin Pregnancy.

Poor uterine tone after the birth of a baby can cause excess bleeding (called postpartum hemorrhage or PPH). This is a major cause of maternal death worldwide. Uterotonic drugs are used to improve the muscle tone of the uterus after birth, and these are effective at reducing the incidence of PPH. The Society of Obstetricians and Gynecologists of Canada (SOGC) has recommended a single dose of 100 mcg of carbetocin at elective cesarean delivery to promote uterine contraction. In a study performed at Mount Sinai Hospital, the investigators have shown that smaller doses of carbetocin (14.8 mcg) are effective in achieving adequate uterine tone at elective cesarean section.

In these dose-finding studies, women with multiple pregnancies have been excluded. Because women with multiple pregnancy have a higher risk of severe PPH, uterine atony, hysterectomy, prolonged hospital stay and death, it is plausible that a higher dose of carbetocin is required. This question remains unanswered.

The hypothesis is that the ED90 of carbetocin in women with twin pregnancy undergoing elective cesarean delivery under regional anesthesia is greater than 20 mcg but less than 100 mcg.

Study Overview

• Status: Completed
• Conditions: Postpartum Hemorrhage; Twin
• Intervention / Treatment: Drug: Carbetocin

Detailed Description

There is a lack of consensus as to what the optimal uterotonic regime is globally. Furthermore, variability in the international guidelines regarding the choice of first line uterotonic in prevention of PPH adds to the confusion. With the widespread availability of carbetocin in some developed countries, including Canada, the question of which uterotonic to adopt and at which dose becomes even more difficult to ascertain. Studies that have currently been published suggest the ED90 doses of carbetocin and oxytocin provide adequate uterine contraction with possibly fewer side effects associated with the lower dose regimens. There is evidence to suggest that lower doses of both carbetocin provide equivalent uterine contractions with a better side effect profile in patients with a singleton pregnancy. However, there is no clinical dosing data specifically for patients with twin pregnancy. The results of our study will provide guidance to obstetric and anesthetic providers worldwide when deciding what dose of carbetocin to use in women with twin pregnancy.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jose Carvalho, MD; Phone Number: 2681 416-586-4800; Email: jose.carvalho@sinaihealthsystem.ca

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Twin Pregnancy
• Elective cesarean delivery under regional anesthesia
• Gestational age ≥ 36 weeks
• No known additional risk factors for postpartum hemorrhage
• Written informed consent to participate in this study

Exclusion Criteria:

• Refusal to give written informed consent
• Allergy or hypersensitivity to oxytocin
• Conditions that may predispose to uterine atony and postpartum hemorrhage such as placenta previa, severe preeclampsia (as defined by SOGC guidelines (25)), polyhydramnios, uterine fibroids, previous history of uterine atony resulting in PPH, or bleeding diathesis and obesity, defined as pre-pregnancy BMI >40
• Hepatic, renal, and vascular disease
• Use of general anesthesia prior to the administration of the study drug

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Carbetocin 10mcg; Patient is given 10mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Carbetocin; Carbetocin administered intravenously, over 1 minute following delivery of the fetal head.; Other Names: Duratocin
Active Comparator: Carbetocin 20mcg; Patient is given 20mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Carbetocin; Carbetocin administered intravenously, over 1 minute following delivery of the fetal head.; Other Names: Duratocin
Active Comparator: Carbetocin 40mcg; Patient is given 40mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Carbetocin; Carbetocin administered intravenously, over 1 minute following delivery of the fetal head.; Other Names: Duratocin
Active Comparator: Carbetocin 60mcg; Patient is given 60mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Carbetocin; Carbetocin administered intravenously, over 1 minute following delivery of the fetal head.; Other Names: Duratocin
Active Comparator: Carbetocin 80mcg; Patient is given 80mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Carbetocin; Carbetocin administered intravenously, over 1 minute following delivery of the fetal head.; Other Names: Duratocin
Active Comparator: Carbetocin 100mcg; Patient is given 100mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Carbetocin; Carbetocin administered intravenously, over 1 minute following delivery of the fetal head.; Other Names: Duratocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine tone 2 minutes: questionnaire	Uterine tone, defined as satisfactory or unsatisfactory by the obstetrician at 2 minutes after completion of the carbetocin injection.	2 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
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 or a heart rate < 50bpm, 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
Uterine tone 5 minutes: questionnaire	Uterine tone, defined as satisfactory or unsatisfactory by the obstetrician at 5 minutes after completion of the carbetocin injection.	5 minutes
Additional uterotonics administered	The drug, dosage and timing of any additional uterotonic medication given during surgery.	1 hour
Estimated blood loss	Blood loss will be calculated through the difference in hematocrit values assessed prior to surgery and 24 hours after the cesarean delivery.	24 hours
Intravenous fluid administered during surgery	The total volume (ml) of fluid administered from entering the operating room to skin closure.	2 hours

Collaborators and Investigators

• Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
• Investigators: Principal Investigator: Jose Carvalho, MD, Mount Sinai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2021
• Primary Completion (Actual): April 27, 2023
• Study Completion (Actual): April 28, 2023

Study Registration Dates

• First Submitted: November 27, 2019
• First Submitted That Met QC Criteria: November 27, 2019
• First Posted (Actual): December 2, 2019

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Pregnancy; cesarean delivery; Postpartum hemorrhage; uterotonic; Twins; carbetocin
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Carbetocin
• Other Study ID Numbers: 19-07

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