Postpartum HemorrhageNCT06285409
Comparing the Dose-response Profiles of Uterotonics After Initial Carbetocin Administration - an Ex-vivo Study in Desensitized Human Myometrium
A study testing Carbetocin, Oxytocin and Ergonovine in people with Postpartum Hemorrhage, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postpartum Hemorrhage
- What is being tested?
- Carbetocin, Oxytocin and Ergonovine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteCanada
- Study dates
- 4 Apr 2024to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Mount Sinai Hospital
Toronto, Ontario, M5G1X5
Mrinalini Balki, MD, 416-586-4800 ext. 5270, mrinalini.balki@uhn.ca
Wafa Bellan, MD
About this study
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.
Read the 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.
- Conditions
- Postpartum Hemorrhage
- Being tested
- Carbetocin, Oxytocin, Ergonovine, Carboprost
- Keywords
- carbetocin, duratocin, oxytocin, uterine contraction
- Medical subject headings
- Postpartum Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarbetocinDrug
Also called Duratocin
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).
OxytocinDrug
Also called Pitocin
Oxytocin 10-5M will be added to all strips for 2 hours to induce desensitization.
CarbetocinDrug
Also called Duratocin
Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-5 M to 10-5 M
OxytocinDrug
Also called Pitocin
Increasing concentrations of oxytocin from 10-10 M to 10-5 M
ErgonovineDrug
Also called Ergometrine
Increasing concentrations of ergometrine from 10-10 M to 10-5 M
CarboprostDrug
Also called Hemabate
Increasing concentrations of carboprost from 10-10 M to 10-5 M
| Study group | Role | What they receive |
|---|---|---|
| Carbetocin | Active comparator | 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 Receives: Drug: Carbetocin; Drug: Oxytocin |
| Oxytocin | Active comparator | Dose-response testing with increasing concentrations of oxytocin from 10-10 M to 10-5 M. Receives: Drug: Carbetocin; Drug: Oxytocin |
| Ergometrine | Active comparator | Dose-response testing with increasing concentrations of ergometrine from 10-10 M to 10-5 M Receives: Drug: Carbetocin; Drug: Oxytocin; Drug: Ergonovine |
| Carboprost | Active comparator | Dose-response testing with increasing concentrations of carboprost from 10-10 M to 10-5 M Receives: Drug: Carbetocin; Drug: Oxytocin; Drug: Carboprost |
| Control | Placebo comparator | No drug added to physiological salt solution (PSS). Receives: Drug: Carbetocin; Drug: Oxytocin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Motility index
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.
Measured: 4 hours
Secondary outcomes (3)
Amplitude of contraction
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.
Measured: 4 hours
Frequency of contraction
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.
Measured: 4 hours
Integrated area under response curve (AUC)
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2024
- Study start4 Apr 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postpartum HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mrinalini Balki, MD, Principal investigator, MOUNT SINAI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06285409
- Sponsor's protocol ID
- 24-02
- Status last verified
- Mar 2026
- First submitted
- 22 Feb 2024
- Last updated
- 6 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing the Dose-response Profiles of Uterotonics After Initial Carbetocin Administration - an Ex-vivo Study in Desensitized Human Myometrium
- ClinicalTrials.gov ID
- NCT06285409
- Acronym / sponsor ID
- 24-02
- Conditions
- Postpartum Hemorrhage
- Keywords
- carbetocin, duratocin, oxytocin, uterine contraction
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- 4 Apr 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 29 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Carbetocin | Active comparator | Drug: Carbetocin, Drug: OxytocinDose-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 |
| Oxytocin | Active comparator | Drug: Carbetocin, Drug: OxytocinDose-response testing with increasing concentrations of oxytocin from 10-10 M to 10-5 M. |
| Ergometrine | Active comparator | Drug: Carbetocin, Drug: Oxytocin, Drug: ErgonovineDose-response testing with increasing concentrations of ergometrine from 10-10 M to 10-5 M |
| Carboprost | Active comparator | Drug: Carbetocin, Drug: Oxytocin, Drug: CarboprostDose-response testing with increasing concentrations of carboprost from 10-10 M to 10-5 M |
| Control | Placebo comparator | Drug: Carbetocin, Drug: OxytocinNo drug added to physiological salt solution (PSS). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- Patient refusal
- Patients who require general anesthesia
- Patients in labour and those receiving oxytocin for induction of labour
- Emergency CD
- placenta accreta spectrum disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarbetocinAlso: DuratocinCarbetocin 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). | Drug | Carbetocin, Carboprost, Control, Ergometrine, Oxytocin |
| OxytocinAlso: PitocinOxytocin 10-5M will be added to all strips for 2 hours to induce desensitization. | Drug | Carbetocin, Carboprost, Control, Ergometrine, Oxytocin |
| CarbetocinAlso: DuratocinIncreasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-5 M to 10-5 M | Drug | Carbetocin |
| OxytocinAlso: PitocinIncreasing concentrations of oxytocin from 10-10 M to 10-5 M | Drug | Oxytocin |
| ErgonovineAlso: ErgometrineIncreasing concentrations of ergometrine from 10-10 M to 10-5 M | Drug | Ergometrine |
| CarboprostAlso: HemabateIncreasing concentrations of carboprost from 10-10 M to 10-5 M | Drug | Carboprost |
Primary outcome
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.
3 secondary outcomes
Amplitude of contraction
Time frame: 4 hours
Frequency of contraction
Time frame: 4 hours
Integrated area under response curve (AUC)
Time frame: 4 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2026.
- Individual participant dataSharing planned: No
Related trials for Postpartum Hemorrhage
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mrinalini Balki, MD principal investigator
MOUNT SINAI HOSPITAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Carbetocin, Oxytocin and Ergonovine in people with Postpartum Hemorrhage, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mrinalini Balki, MD (416-586-4800 ext. 5270, mrinalini.balki@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Motility index (time frame: 4 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2026.