Effect of Extracellular Calcium on Carbetocin Mediated Contractility in Human Myometrium

September 22, 2025 updated by: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Effect of Extracellular Calcium on Carbetocin Mediated Contractility in Human Myometrium: An Ex-Vivo Study

Postpartum hemorrhage (PPH) continues to be an increasing problem globally. Uterotonics play an essential role in the pharmacological management of uterine atony. Carbetocin, a long acting analog of oxytocin has been recommended as a first line uterotonic for PPH prophylaxis at cesarean delivery. Considering many woman have associated comorbidities and are at high risk of PPH, finding alternative pharmacological agents is essential. Calcium is a key factor for myometrial contractions and calcium blood levels can be low at the end of pregnancy. Both hypocalcemia and hypercalcemia could lead to a decrease in myometrial contractions. It is already been demonstrated that in both desensitized and naïve myometrium, normocalcemia provides a better uterine tone compared to hypo and hypercalcemia when oxytocin is given as the first uterotonic drug.

Currently, the role of extracelullar calcium in carbetocin- induced contractility is unknown. This will be the first ex vivo study to test the effects of extracellular calcium on oxytocin pretreated and naive myometrium. The results of this study will provide evidence on the use of this safe drug in clinical practice, particularly in women with labour arrest, and provide alternative pharmacological strategies to both prevention and treatment of PPH, thus improving our clinical practice.

The investigators hypothesize that extracellular normocalcemia would provide superior carbetocin-mediated contractility in both naive and oxytocin-pretreated myometrium compared with hypercalcemia and hypocalcemia.

Study Overview

Status

Status

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

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

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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 (Estimated)

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.
40

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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G1X5
        • Recruiting
        • Mount Sinai Hospital
        • Principal Investigator:
          • Mrinalini Balki, MD
        • Sub-Investigator:
          • Ronald George, MD
        • Contact:
        • Sub-Investigator:
          • Joseph Park, BSc
        • Sub-Investigator:
          • Anuradha Baishnob, BSc
        • Sub-Investigator:
          • Nicolas Muller, 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

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

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • non-laboring women with gestational age between 37 to 41 weeks
  • not exposed to exogenous oxytocin, scheduled for a primary or first repeat cesarean delivery under neuraxial anesthesia.

Exclusion criteria:

  • patients requiring general anesthesia
  • more than 1 previous cesarean delivery
  • history of uterine atony
  • emergency cesarean section in labor
  • patients using medications that could affect myometrial contractility such as nifedipine, labetalol, or magnesium sulphate.
  • patients with any condition of predisposing to uterine atony and postpartum hemorrhage, such as abnormal placentation, multiple gestation, severe preeclampsia, macrosomia, polyhydroamnios, large uterine fibroids, chorioamnionitis, previous history of postpartum bleeding.

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

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: Calcium 1.25nM with NO oxytocin pre-exposure
Dose-response testing with 1.25nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with NO oxytocin pre-exposure
Drug: Carbetocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M
Drug: Calcium
Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.
Active Comparator: Calcium 2.5nM with NO oxytocin pre-exposure
Dose-response testing with 2.5nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with NO oxytocin pre-exposure
Drug: Carbetocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M
Drug: Calcium
Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.
Active Comparator: Calcium 5.0nM with NO oxytocin pre-exposure
Dose-response testing with 5.0nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with NO oxytocin pre-exposure
Drug: Carbetocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M
Drug: Calcium
Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.
Active Comparator: Calcium 1.25nM with oxytocin pre-exposure
Dose-response testing with 1.25nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with oxytocin pre-exposure
Drug: Carbetocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M
Drug: Calcium
Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.
Drug: Oxytocin
Oxytocin 10-5M will be added to 3 groups of myometrial strips for 2 hours to induce desensitization.
Active Comparator: Calcium 2.5nM with oxytocin pre-exposure
Dose-response testing with 2.5nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with oxytocin pre-exposure
Drug: Carbetocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M
Drug: Calcium
Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.
Drug: Oxytocin
Oxytocin 10-5M will be added to 3 groups of myometrial strips for 2 hours to induce desensitization.
Active Comparator: Calcium 5.0nM with oxytocin pre-exposure
Dose-response testing with 5.0nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with oxytocin pre-exposure
Drug: Carbetocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M
Drug: Calcium
Calcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.
Drug: Oxytocin
Oxytocin 10-5M will be added to 3 groups of myometrial strips for 2 hours to induce desensitization.

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
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

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
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

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.
September 15, 2025

Primary Completion (Estimated)

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.
June 1, 2026

Study Completion (Estimated)

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.
June 1, 2026

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).
April 9, 2025

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.
April 9, 2025

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.
April 16, 2025

Study Record Updates

Last Update Posted (Estimated)

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.
September 24, 2025

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.
September 22, 2025

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.
September 1, 2025

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.
  • 25-01 (St. Francis Hospital IRB)

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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