Postpartum HemorrhageNCT03434444
In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol
A study testing Oxytocin and Propranolol in people with Postpartum Hemorrhage, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site in Canada.
Trial summary
The rates of cesarean deliveries (CD) and postpartum hemorrhage (PPH) are on the rise, with failed induction and augmentation of labor as major contributing factors. Oxytocin is commonly used for labor induction, as well as during the third stage of labor to minimize the risk of primary PPH. Read more about this study
- Who is it for?
- Ages 16 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postpartum Hemorrhage
- What is being tested?
- Oxytocin and Propranolol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteCanada
- Study dates
- 8 Sep 2017to 20 Aug 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 16 to 40 years
- Women only
- Healthy volunteers accepted
- Child, 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 primary Cesarean delivery or first repeat Cesarean delivery
Who cannot join
- Patients who refuse to give written informed consent
- Patients who require general anesthesia
- Patients who had previous uterine surgery or more than one previous Cesarean delivery
- Patients with any condition predisposing to uterine atony and postpartum hemorrhage, such as abnormal placentation, multiple gestation, preeclampsia, macrosomia, polyhydramnios, uterine fibroids, bleeding diathesis, chorioamnionitis, or a previous history of postpartum bleeding
- Emergency Cesarean section in labor
- Patients on medications that could affect myometrial contractility, such as nifedipine, labetolol or magnesium sulfate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol - Potential Applications in Induction of Labour and Treatment of Postpartum Hemorrhage
The rates of cesarean deliveries (CD) and postpartum hemorrhage (PPH) are on the rise, with failed induction and augmentation of labor as major contributing factors. Oxytocin is commonly used for labor induction, as well as during the third stage of labor to minimize the risk of primary PPH. At delivery, it is imperative that the uterus responds effectively to parenteral oxytocin. Poor response to oxytocin following delivery is commonly due to prolonged labor with oxytocin augmentation that is known to "desensitize" the myometrium. Despite the option of several second line uterotonic agents, none of them are as effective as oxytocin in controlling PPH. Given that poor uterine muscle contraction is the root cause of both failed induction or augmentation (leading to a CD in labor) and uterine atony (leading to PPH), there is an urgent and clinically important need to investigate novel methods to enhance oxytocin-induced myometrial contractions.
Propranolol, a beta adrenergic receptor agonist, has the potential to improve myometrial contractions by virtue of its ability to inhibit catecholamine production. The investigators plan to investigate the effects of propranolol in both naive and desensitized myometrium, in order to better understand its potential role in improving labor induction and reducing the risk of PPH following oxytocin exposure during labor.
The investigators hypothesize that propranolol is likely to potentiate the action of oxytocin upon human myometrium, to ultimately help improve the success of labor induction/augmentation and treatment of PPH.
Read the detailed description
Myometrial samples will be used to investigate the effect of propranolol on uterine contractions when exposed to high and low doses of oxytocin (to simulate PPH treatment and labor induction respectively).
The tissue will also be frozen at the end of the experiment, and Western blotting will be used to investigate the effect of propranolol on the expression patterns and cellular distribution of the oxytocin receptor and beta-adrenergic receptor and their signaling pathways in desensitized myometrium.
- Conditions
- Postpartum Hemorrhage
- Being tested
- Oxytocin, Propranolol
- Keywords
- propranolol, 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.
OxytocinDrug
Also called pitocin
Oxytocin in solution, ranging from 10 -12M to 10 -5M
PropranololDrug
Propranolol in solution, 10-6M
| Study group | Role | What they receive |
|---|---|---|
| Low Dose Oxytocin | Active comparator | The myometrial samples are bathed in an oxytocin solution at increasing concentrations (from 10 -12M to 10 -9M) Receives: Drug: Oxytocin |
| Propranolol | Active comparator | The myometrial samples are bathed in a propranol solution at 10 -6M Receives: Drug: Propranolol |
| Propranolol + low dose oxytocin | Active comparator | The myometrial samples are bathed in an oxytocin solution at increasing concentrations (from 10 -12M to 10 -9M) plus propranol (10 -6M) Receives: Drug: Oxytocin; Drug: Propranolol |
| High Dose Oxytocin | Active comparator | The myometrial samples are bathed in an oxytocin solution (10 -5M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M) Receives: Drug: Oxytocin |
| High Dose Oxytocin, Propranolol-pretreated | Active comparator | The myometrial samples are bathed in an oxytocin solution (10 -5M) plus propranolol (10 -6M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M) Receives: Drug: Oxytocin; Drug: Propranolol |
| High dose oxytocin + propranolol | Active comparator | The myometrial samples are bathed in an oxytocin solution (10 -5M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M) plus propranolol (10 -6M) Receives: Drug: Oxytocin; Drug: Propranolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Motility index
Motility index (MI) takes into account both the amplitude and frequency of the myometrial contraction. It is a calculated outcome, based on the formula: frequency/(10 x amplitude).
The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.
Measured: 3 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: 3 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: 3 hours
Integrated area under response curve (AUC)
Measured: 3 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2018
- Study start8 Sep 2017
- Primary completion19 Aug 2022
- Study completion20 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
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
- NCT03434444
- Sponsor's protocol ID
- 18-04
- Status last verified
- Feb 2023
- First submitted
- 9 Feb 2018
- Last updated
- 24 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Balki M, Miller LM, Caliaperumal J, Wang S, Huszti E, Kingdom JC. Propranolol and Oxytocin-Induced Contractility in Gravid Human Myometrium: An Ex Vivo Laboratory Study. BJOG. 2025 Aug;132(9):1228-1237. doi: 10.1111/1471-0528.18146. Epub 2025 Mar 24.
PubMed 40129234
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol - Potential Applications in Induction of Labour and Treatment of Postpartum Hemorrhage
- ClinicalTrials.gov ID
- NCT03434444
- Acronym / sponsor ID
- 18-04
- Conditions
- Postpartum Hemorrhage
- Keywords
- propranolol, oxytocin, uterine contraction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- 8 Sep 2017 (actual)
- Primary completion
- 19 Aug 2022 (actual)
- Study completion
- 20 Aug 2022 (actual)
- First posted
- 15 Feb 2018 (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.
The rates of cesarean deliveries (CD) and postpartum hemorrhage (PPH) are on the rise, with failed induction and augmentation of labor as major contributing factors. Oxytocin is commonly used for labor induction, as well as during the third stage of labor to minimize the risk of primary PPH. At delivery, it is imperative that the uterus responds effectively to parenteral oxytocin. Poor response to oxytocin following delivery is commonly due to prolonged labor with oxytocin augmentation that is known to "desensitize" the myometrium. Despite the option of several second line uterotonic agents, none of them are as effective as oxytocin in controlling PPH. Given that poor uterine muscle contraction is the root cause of both failed induction or augmentation (leading to a CD in labor) and uterine atony (leading to PPH), there is an urgent and clinically important need to investigate novel methods to enhance oxytocin-induced myometrial contractions.
Propranolol, a beta adrenergic receptor agonist, has the potential to improve myometrial contractions by virtue of its ability to inhibit catecholamine production. The investigators plan to investigate the effects of propranolol in both naive and desensitized myometrium, in order to better understand its potential role in improving labor induction and reducing the risk of PPH following oxytocin exposure during labor.
The investigators hypothesize that propranolol is likely to potentiate the action of oxytocin upon human myometrium, to ultimately help improve the success of labor induction/augmentation and treatment of PPH.
Detailed description
Myometrial samples will be used to investigate the effect of propranolol on uterine contractions when exposed to high and low doses of oxytocin (to simulate PPH treatment and labor induction respectively).
The tissue will also be frozen at the end of the experiment, and Western blotting will be used to investigate the effect of propranolol on the expression patterns and cellular distribution of the oxytocin receptor and beta-adrenergic receptor and their signaling pathways in desensitized myometrium.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Low Dose Oxytocin | Active comparator | Drug: OxytocinThe myometrial samples are bathed in an oxytocin solution at increasing concentrations (from 10 -12M to 10 -9M) |
| Propranolol | Active comparator | Drug: PropranololThe myometrial samples are bathed in a propranol solution at 10 -6M |
| Propranolol + low dose oxytocin | Active comparator | Drug: Oxytocin, Drug: PropranololThe myometrial samples are bathed in an oxytocin solution at increasing concentrations (from 10 -12M to 10 -9M) plus propranol (10 -6M) |
| High Dose Oxytocin | Active comparator | Drug: OxytocinThe myometrial samples are bathed in an oxytocin solution (10 -5M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M) |
| High Dose Oxytocin, Propranolol-pretreated | Active comparator | Drug: Oxytocin, Drug: PropranololThe myometrial samples are bathed in an oxytocin solution (10 -5M) plus propranolol (10 -6M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M) |
| High dose oxytocin + propranolol | Active comparator | Drug: Oxytocin, Drug: PropranololThe myometrial samples are bathed in an oxytocin solution (10 -5M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M) plus propranolol (10 -6M) |
Who may qualify
- Ages
- 16 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 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 primary Cesarean delivery or first repeat Cesarean delivery
Key exclusion criteria (6 listed)
- Patients who refuse to give written informed consent
- Patients who require general anesthesia
- Patients who had previous uterine surgery or more than one previous Cesarean delivery
- Patients with any condition predisposing to uterine atony and postpartum hemorrhage, such as abnormal placentation, multiple gestation, preeclampsia, macrosomia, polyhydramnios, uterine fibroids, bleeding diathesis, chorioamnionitis, or a previous history of postpartum bleeding
- Emergency Cesarean section in labor
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 |
|---|---|---|
| OxytocinAlso: pitocinOxytocin in solution, ranging from 10 -12M to 10 -5M | Drug | High Dose Oxytocin, High Dose Oxytocin, Propranolol-pretreated, High dose oxytocin + propranolol, Low Dose Oxytocin, Propranolol + low dose oxytocin |
| PropranololPropranolol in solution, 10-6M | Drug | High Dose Oxytocin, Propranolol-pretreated, High dose oxytocin + propranolol, Propranolol, Propranolol + low dose oxytocin |
Primary outcome
Motility index
Time frame: 3 hours
Motility index (MI) takes into account both the amplitude and frequency of the myometrial contraction. It is a calculated outcome, based on the formula: frequency/(10 x amplitude). 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: 3 hours
Frequency of contraction
Time frame: 3 hours
Integrated area under response curve (AUC)
Time frame: 3 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2023.
- Derived from this study: PubMed 40129234Balki M, Miller LM, Caliaperumal J, Wang S, Huszti E, Kingdom JC. Propranolol and Oxytocin-Induced Contractility in Gravid Human Myometrium: An Ex Vivo Laboratory Study. BJOG. 2025 Aug;132(9):1228-1237. doi: 10.1111/1471-0528.18146. Epub 2025 Mar 24.
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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. This study is not recruiting at the moment.
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 Oxytocin and Propranolol 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 4 inclusion and 6 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: finished, as of the sponsor's last update on 24 Feb 2023. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Motility index (time frame: 3 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03434444, which also lists 1 linked publication.
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 24 Feb 2023.