Comparing the Dose-response Profiles of Uterotonics After Initial Carbetocin Administration - an Ex-vivo Study in Desensitized Human Myometrium

March 31, 2026 updated by: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

This study will investigate the effects of drugs called "uterotonics" that help with the contraction of the uterus after a baby is born. This uterine contraction is very important to stop the bleeding after delivery. An uncontracted uterine state is called "uterine atony", which can lead to an excessive amount of post-delivery bleeding. Carbetocin is an uterotonic drug that works well to prevent post-delivery bleeding. In some cases, carbetocin is not enough to contract the uterus, and ongoing bleeding continues. When that happens, there are other uterotonic medications that can be used. In this study, we aim to find which uterotonic drug, amongst those available (oxytocin, carbetocin, ergometrine or carboprost), is more effective to lower the risk of post-delivery bleeding once carbetocin has already been administered.

This study will be done by using a very small sample of uterine tissue, taken from the incision site, following delivery by cesarean section. The sample is taken to the laboratory and will be exposed to carbetocin followed by other uterotonic drugs. The information obtained from this study will help modify the treatment for uterine atony and post-delivery bleeding to lower the risk further.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Postpartum hemorrhage (PPH) remains to be one of the leading causes of maternal morbidity and mortality. It has been noted that an increasing number of PPH is attributed to the increased incidence of uterine atony. Carbetocin is the first line therapy for prevention and treatment of uterine atony. Carbetocin is currently used as a single dose treatment without an option of redosing. It has been proven that exposure to oxytocin during labour results in a decrease in myometrial contractions, previous studies shows that the current dose of carbetocin (100 µcg) is insufficient for optimal uterine contraction in failure to progress caesarean section.

According to current guidelines for medical management of PPH, the first line therapy for post CD uterotonic agent in Canada is carbetocin. It is a reliable and safe agent; however, it is a "one shot" option for treatment due to its longer half-life (40 minutes). The clinicians are reluctant to re-dose carbetocin after an initial failure to achieve adequate uterine tone with the assumption that the oxytocin receptors would likely be saturated with the agonist. It is unknown whether re-dosing with oxytocics (carbetocin or oxytocin) would help augment myometrial contractions, thereby lowering post-partum bleeding and improving patient outcomes. It is also unknown if prior carbetocin administration would affect myometrial contractility induced by other second line uterotonics such as ergometrine or carboprost.

This study is essential to answer the clinical question of the efficacy of re-dosing with either oxytocics or second line agents uterotonics following the first prophylactic dose of carbetocin in women with previously desensitized myometrium. This will help us better understand the comparative myometrial contractility response for a range of uterotonics.

The primary hypothesis of this study is that treating a second dose of oxytocics(carbetocin/oxytocin) in oxytocin pre-treated myometrium, after the first standard bolus of 100 µcg carbetocin will cause enhanced myometrial contraction compared to control.

The second hypothesis is that the efficacy of second line agents (ergometrine or carboprost) would not be as effective, i.e. they are likely to be less effective than oxytocics.

Study Type

Interventional

Enrollment (Estimated)

32

Phase

  • 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 Contact

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G1X5
        • Recruiting
        • Mount Sinai Hospital
        • Sub-Investigator:
          • Ronald George, MD
        • Contact:
        • Sub-Investigator:
          • Joseph Park, BSc
        • Sub-Investigator:
          • Anuradha Baishnob, BSc
        • Sub-Investigator:
          • Wafa Bellan, MD

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

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion criteria

  • Patients who give written consent to participate in this study
  • Patients with gestational age 37-41 weeks
  • Non-laboring patients, not exposed to exogenous oxytocin
  • Patients requiring elective primary or first repeat CD
  • Patients undergoing CD under spinal anesthesia

Exclusion criteria

  • Patient refusal
  • Patients who require general anesthesia
  • Patients in labour and those receiving oxytocin for induction of labour
  • Emergency CD
  • placenta accreta spectrum disorder
  • Patients who have had previous uterine surgery or >1 previous CD
  • Patients with any condition predisposing to uterine atony and PPH (BMI > 40 kg/m2,
  • Patients on medications that could affect myometrial contractility, such as insulin, nifedipine, labetalol or magnesium sulphate.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Carbetocin
Dose-response testing with increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-5 M to 10-5 M
Drug: Carbetocin
Carbetocin first bolus 10-8 M (equivalent to 100 mcg) will be added to the muscle bath to create ex-vivo environment similar to Cesarean delivery, and after 20 minutes the baths will be washed three time with physiological salt solution (PSS).
Other Names:
  • Duratocin
Drug: Oxytocin
Oxytocin 10-5M will be added to all strips for 2 hours to induce desensitization.
Other Names:
  • Pitocin
Drug: Carbetocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-5 M to 10-5 M
Other Names:
  • Duratocin
Drug: Oxytocin
Increasing concentrations of oxytocin from 10-10 M to 10-5 M
Other Names:
  • Pitocin
Active Comparator: Oxytocin
Dose-response testing with increasing concentrations of oxytocin from 10-10 M to 10-5 M.
Drug: Carbetocin
Carbetocin first bolus 10-8 M (equivalent to 100 mcg) will be added to the muscle bath to create ex-vivo environment similar to Cesarean delivery, and after 20 minutes the baths will be washed three time with physiological salt solution (PSS).
Other Names:
  • Duratocin
Drug: Oxytocin
Oxytocin 10-5M will be added to all strips for 2 hours to induce desensitization.
Other Names:
  • Pitocin
Drug: Carbetocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-5 M to 10-5 M
Other Names:
  • Duratocin
Drug: Oxytocin
Increasing concentrations of oxytocin from 10-10 M to 10-5 M
Other Names:
  • Pitocin
Active Comparator: Ergometrine
Dose-response testing with increasing concentrations of ergometrine from 10-10 M to 10-5 M
Drug: Carbetocin
Carbetocin first bolus 10-8 M (equivalent to 100 mcg) will be added to the muscle bath to create ex-vivo environment similar to Cesarean delivery, and after 20 minutes the baths will be washed three time with physiological salt solution (PSS).
Other Names:
  • Duratocin
Drug: Oxytocin
Oxytocin 10-5M will be added to all strips for 2 hours to induce desensitization.
Other Names:
  • Pitocin
Drug: Carbetocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-5 M to 10-5 M
Other Names:
  • Duratocin
Drug: Oxytocin
Increasing concentrations of oxytocin from 10-10 M to 10-5 M
Other Names:
  • Pitocin
Drug: Ergonovine
Increasing concentrations of ergometrine from 10-10 M to 10-5 M
Other Names:
  • Ergometrine
Active Comparator: Carboprost
Dose-response testing with increasing concentrations of carboprost from 10-10 M to 10-5 M
Drug: Carbetocin
Carbetocin first bolus 10-8 M (equivalent to 100 mcg) will be added to the muscle bath to create ex-vivo environment similar to Cesarean delivery, and after 20 minutes the baths will be washed three time with physiological salt solution (PSS).
Other Names:
  • Duratocin
Drug: Oxytocin
Oxytocin 10-5M will be added to all strips for 2 hours to induce desensitization.
Other Names:
  • Pitocin
Drug: Carbetocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-5 M to 10-5 M
Other Names:
  • Duratocin
Drug: Oxytocin
Increasing concentrations of oxytocin from 10-10 M to 10-5 M
Other Names:
  • Pitocin
Drug: Carboprost
Increasing concentrations of carboprost from 10-10 M to 10-5 M
Other Names:
  • Hemabate
Placebo Comparator: Control
No drug added to physiological salt solution (PSS).
Drug: Carbetocin
Carbetocin first bolus 10-8 M (equivalent to 100 mcg) will be added to the muscle bath to create ex-vivo environment similar to Cesarean delivery, and after 20 minutes the baths will be washed three time with physiological salt solution (PSS).
Other Names:
  • Duratocin
Drug: Oxytocin
Oxytocin 10-5M will be added to all strips for 2 hours to induce desensitization.
Other Names:
  • Pitocin
Drug: Carbetocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-5 M to 10-5 M
Other Names:
  • Duratocin
Drug: Oxytocin
Increasing concentrations of oxytocin from 10-10 M to 10-5 M
Other Names:
  • Pitocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Motility index
Time Frame: 4 hours

Motility index (MI) is a calculated outcome, based on the formula: frequency/(10 x amplitude).

Frequency and amplitude are secondary outcome measures as described below.

The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.
4 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Integrated area under response curve (AUC)
Time Frame: 4 hours
4 hours
Amplitude of contraction
Time Frame: 4 hours
The maximum extent of uterine muscle contraction, measured in grams (g). The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.
4 hours
Frequency of contraction
Time Frame: 4 hours
The number of contractions in uterine muscle (myometrium) over 10 minutes, spontaneously and in response to an agonist. The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.
4 hours

Collaborators and Investigators

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

Sponsor

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Investigators

  • Principal Investigator: Mrinalini Balki, MD, 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)

April 4, 2024

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

February 22, 2024

First Submitted That Met QC Criteria

February 22, 2024

First Posted (Actual)

February 29, 2024

Study Record Updates

Last Update Posted (Actual)

April 6, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24-02

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

product manufactured in and exported from the U.S.

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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