Carbetocin vs. Oxytocin at Elective Cesarean Section

March 2, 2021 updated by: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Carbetocin vs. Oxytocin at Elective Cesarean Section: a Double-blind, Randomized Controlled Non-inferiority Trial of High and Low Dose Regimens

The study investigators are comparing 2 drugs (oxytocin and carbetocin) at 2 different dosages, to help prevent serious bleeding (hemorrhage) after cesarean deliveries. These drugs are used routinely to help contract the uterus and keep it contracted after the delivery of the baby and placenta; this reduces the amount of blood you might lose. At Mount Sinai Hospital, currently oxytocin is used, but its effect on the uterus is much shorter than that of carbetocin. Internationally, there is no consensus as to what the most effective drug to use is and at which dose. The Society of Obstetricians and Gynaecologists of Canada has recently revised its guidelines to suggest 100 micrograms (mcg) of carbetocin as the drug of choice at elective cesarean section. Guidelines from the United Kingdom and the United States currently suggest oxytocin at various doses as the drug of choice at elective cesarean sections. Previous studies at Mount Sinai Hospital have shown that lower doses of oxytocin, 0.35 International Units (IU), and carbetocin, 20 mcg, may be as effective as the higher recommended doses. The investigators plan to conduct a large study to confirm these findings so that they can use the most appropriate dose in the future. Furthermore, the investigators hope to demonstrate that side effects are lower with the lower dose regimens.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Postpartum hemorrhage (PPH) is a major cause of maternal death worldwide. Oxytocin is the most commonly used uterotonic drug to prevent and treat PPH in the world. However, oxytocin has a very short duration of action, requiring a continuous infusion to achieve sustained uterotonic activity. Moreover, large doses are associated with adverse effects like hypotension, nausea, vomiting, dysrhythmias and ST changes. The Society of Obstetricians and Gynecologists of Canada (SOGC) has recommended a single dose of 100 mcg of the longer acting carbetocin at elective cesarean section to promote uterine contraction. In multiple studies performed at Mount Sinai Hospital, we have shown that smaller doses of oxytocin (ED 90 0.35 IU) and carbetocin (ED 90 14.8 mcg) are effective in achieving adequate uterine tone at elective cesarean section. No study has directly compared the high dose regimens with the low dose regimens; therefore a large double-blind randomized controlled trial is necessary to show the non-inferiority of the lower doses of both drugs.

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 of the 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 dosed regimens. These advantages may provide a better safety profile and patient satisfaction. To the best of our knowledge, no studies have compared the low doses (ED90) of oxytocin vs. carbetocin, or low (ED90) vs high (conventional) doses of the two drugs in the setting of elective cesarean section. The results of this study will provide evidence on the efficacy and safety of the ED90 dosing compared directly to the higher dosing of both drugs.

Our hypothesis is that the ED90 doses of carbetocin and oxytocin will not be inferior to the higher dosing as determined by the intensity of uterine contraction using a VNRS in women undergoing elective cesarean section. We anticipate that the intensity of uterine contraction using the VNRS at 2 minutes post administration of all drugs will fall within the predetermined margin to signify non-inferiority of all regimens.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
278

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • McMaster University Medical Centre (MUMC)
      • Toronto, Ontario, Canada, M5G1X5
        • Mount Sinai Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 46 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Elective cesarean section under spinal anesthesia.
  • Written informed consent to participate in this study.
  • Full-term pregnancy
  • Non labouring patients

Exclusion Criteria:

  • Refusal to give written informed consent.
  • Allergy or hypersensitivity to carbetocin or oxytocin.
  • Labouring patients
  • Need for general anesthesia
  • 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.
  • Hepatic, renal, and cardiovascular disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Carbetocin 20mcg
Carbetocin 20mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Drug: Carbetocin
Patient is given carbetocin (20 or 100 mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Other Names:
  • Duratocin
Active Comparator: Carbetocin 100mcg
Carbetocin 100mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Drug: Carbetocin
Patient is given carbetocin (20 or 100 mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Other Names:
  • Duratocin
Active Comparator: Oxytocin 0.5IU
Oxytocin 0.5IU, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Drug: Oxytocin
Patient is given oxytocin (0.5 or 5 IU) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Other Names:
  • Pitocin
Active Comparator: Oxytocin 5IU
Oxytocin 5IU, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Drug: Oxytocin
Patient is given oxytocin (0.5 or 5 IU) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Other Names:
  • Pitocin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Uterine Tone 2 minutes
Time Frame: 2 minutes
Intensity of uterine tone on a VNRS scale of 0-10 as evaluated by the obstetrician at 2 minutes after completion of injection of the bolus study drug.
2 minutes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hypotension: systolic blood pressure less than 80% of baseline
Time Frame: 2 hours
Systolic blood pressure < 80% of baseline, from drug administration until end of surgery
2 hours
Hypertension: systolic blood pressure greater than 120% of baseline
Time Frame: 2 hours
Systolic blood pressure > 120% of baseline, from drug administration until end of surgery
2 hours
Tachycardia: heart rate greater than 130% of baseline
Time Frame: 2 hours
Heart rate > 130% of baseline, from drug administration until end of surgery
2 hours
Presence of ventricular tachycardia: ECG
Time Frame: 2 hours
Presence of ventricular tachycardia as recorded by ECG, from drug administration until end of surgery
2 hours
Presence of atrial fibrillation: ECG
Time Frame: 2 hours
Presence of atrial fibrillation as recorded by ECG, from drug administration until end of surgery
2 hours
Presence of atrial flutter: ECG
Time Frame: 2 hours
Presence of atrial flutter as recorded by ECG, from drug administration until end of surgery
2 hours
Presence of nausea: questionnaire
Time Frame: 2 hours
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
Time Frame: 2 hours
The presence of vomiting and number of episodes, from drug administration until end of surgery
2 hours
Presence of chest pain: questionnaire
Time Frame: 2 hours
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
Time Frame: 2 hours
Any presence of shortness of breath, from drug administration until end of surgery, as reported by the patient
2 hours
Presence of headache: questionnaire
Time Frame: 2 hours
Any presence of headache, from drug administration until end of surgery, as reported by the patient
2 hours
Uterine Tone 5 minutes
Time Frame: 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 minutes
Uterine Tone 10 minutes
Time Frame: 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 minutes
Additional uterotonics - operating room
Time Frame: 1 hour
The use of additional uterotonic agents in the operating room
1 hour
Additional uterotonics - 24 hours
Time Frame: 24 hours
The use of additional uterotonic agents at any time after admission to the recovery room and up to 24 hours post delivery
24 hours
Estimated blood loss
Time Frame: 24 hours
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
Bradycardia: heart rate less than 70% of baseline
Time Frame: 2 hours
Heart rate < 70% of baseline, from drug administration until end of surgery
2 hours
Presence of flushing: questionnaire
Time Frame: 2 hours
Any presence of flushing, from drug administration until end of surgery
2 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 25, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 17, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 18, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 23, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 24, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 30, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 3, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 2, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 17-01

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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