Postpartum HemorrhageNCT06285396
Effect of Ephedrine, Phenylepinephrine, and Norepinephrine on Myometrial Contractility in Pregnant People With Type II and Gestational Diabetes During Cesarean Section: An In-vitro Study
A study testing Ephedrine, Phenylephrine and Norepinephrine in people with Postpartum Hemorrhage, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site in Canada.
Trial summary
The goal of this study is to learn about how medication that is used to help treat low blood pressure during a Cesarean delivery (CD) can cause changes to the uterine muscle tissue and its ability to contract, in patients with Type II and gestational diabetes. Read more about this study
- Who is it for?
- Ages 19 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postpartum Hemorrhage
- What is being tested?
- Ephedrine, Phenylephrine and Norepinephrine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteCanada
- Study dates
- 18 Mar 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 19 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Patients who have given consent to participate in the study
- Patients with gestational age 37-41 weeks
- Patients previously diagnosed with either Type II or Gestational diabetes. For the healthy control group, no previous diagnosis is required for inclusion
- Patients of 19-45 years
- Patients of normal BMI (18-30 BMI) for the healthy control group only
- Baby is registered as normal weight for size for the healthy control group only
Show all 9Show fewer
- Non-laboring patients, not exposed to exogenous oxytocin
- Patients requiring elective primary or first repeat caesarean delivery
- Patients undergoing caesarean delivery under spinal anesthesia
Who cannot join
- Patients who refuse to give written informed consent
- Patients who require general anesthesia
- Patients in labor and those receiving oxytocin for induction of labor
- Emergency caesarean delivery in labor
- Patients who have had previous uterine surgery involving myometrial dissection or >1 previous caesarean delivery
- Patients with risk factors for PPH such as those with polyhydramnios, preeclampsia, multiple gestation, morbid obesity, macrosomia (large for size baby), and previous history of PPH. However, for diabetic group, those with morbid obesity and macrosomia will not be excluded as these conditions are almost always associated with diabetes.
- For the healthy control group only, a BMI >30 or <18
- Maternal age >45
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
Caroline Carruthers
About this study
The goal of this study is to learn about how medication that is used to help treat low blood pressure during a Cesarean delivery (CD) can cause changes to the uterine muscle tissue and its ability to contract, in patients with Type II and gestational diabetes.
Spinal anesthesia administered during elective CD has been known to cause hypotension (low blood pressure) as a side effect during the procedure, and is prevented by administration of vasopressors (medication to raise blood pressure) by the anesthesiologist after the delivery of the baby. Vasopressors treat hypotension by interacting with receptors on blood vessels that increase blood pressure, which can also cause changes to uterine contractility. Inadequate uterine contraction after CD can expose mothers to postpartum hemorrhage (PPH), with diabetic patients displaying a 2.5-times higher risk of PPH.
It is important to understand how vasopressor(s) might affect the uterine contractility of women with Type II and gestational diabetes. Since medication to contract the uterus is also routinely administered at delivery, it is important to study the effect of these drugs in combination. The purpose of this study is to compare uterine contractility patterns and receptor distribution in women with type II and gestational diabetic and control term pregnant patients with administration of vasopressors. This will be done using small uterine tissue samples taken from the incision site following CD, which will then be used for experiments in the laboratory.
Read the detailed description
The global prevalence of diabetes has increased drastically over the past 20 years, with 1.5 million new cases each year. The prevalence of Type II diabetes in women of childbearing age has shown the greatest increase, in the United States alone rising from 33% in 1990-1998 to 70% in 2020. Additionally, the worldwide rate of cesarean delivery (CD) follows a similar trend. CD procedures can be both elective and emergent, with the rate of elective CD increasing by 30% in Canada since 2001. Neuraxial anesthesia administered during elective CD has been known to induce hypotension as a side effect, which is then countered by administering vasopressors such as epinephrine, norepinephrine, and phenylephrine that act on adrenergic alpha and beta receptors on smooth muscle tissue. However, since these receptors are expressed on the smooth muscle layer of the uterus called the myometrium, vasopressors can elicit changes in myometrial contractility. Inadequate myometrial contractility during CD can expose the mother to postpartum hemorrhage (PPH) which is a leading cause of maternal mortality worldwide.
Additionally, diabetic women undergoing CD are often obese (BMI > 30 kg/m2) or have macrosomia (larger than average baby), which are independent risk factors for PPH. However, there is still a 2.5-fold increased risk in PPH in Type II diabetic patients, even when adjusted for diabetic-associated obesity. Type II diabetics undergoing elective CD also display a reduced contractile profile (as previously explored through in-vitro calcium signaling), which may contribute to their increased risk of PPH. Current research on myometrial contractility shows that throughout the gestational period, the adrenergic receptor subtypes on the myometrial tissue may transition to more pro-contractile phenotypes, which may react differently to administered vasopressors and thus affect induced contractility during CD. Oxytocin, a uterotonic, is the standard treatment for preventing PPH administered immediately after delivery.
There is currently no literature on the unique effects of vasopressors to manage hypotension in obstetric patients who are diagnosed with Type II and gestational diabetes. The increased risk of PPH at CD seen in type II and Gestational diabetics mothers may be due to differences in adrenergic receptor distribution, which have different affinities to the vasopressors administered. No studies thus far have directly explored the role of vasopressors on myometrial contractions in this patient population.
As the use of a standardized vasopressor dosage becomes more routine during elective CD, it is important to understand how this will affect the myometrial contractility of women with Type II and gestational diabetes. The investigators hypothesize that administration of vasopressors in full term pregnant women with type II and gestational diabetes will cause decreased myometrial contractility compared to healthy controls, and that the diabetic tissue will possess a different adrenergic receptor subtype profile compared to controls.
Aim 1: Investigate the differences in myometrial contractility of type II and gestational diabetic vs. control term pregnant patients with administration of vasopressors
Aim 2: Determine the expression of adrenergic receptor subtypes on myometrium of term pregnant type II and gestational diabetic patients
Aim 3: Investigate the difference in downstream adrenergic pathways proteins in myometrial of type II and gestational diabetics vs control patients with administration of vasopressors
- Conditions
- Postpartum Hemorrhage
- Being tested
- Ephedrine, Phenylephrine, Norepinephrine, Oxytocin
- Keywords
- oxytocin, type II diabetes, gestational diabetes, uterine contraction
- Medical subject headings
- Postpartum Hemorrhage, Diabetes Mellitus, Type 2, Diabetes, Gestational
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EphedrineDrug
Ephedrine in solution, at applicable concentrations based on literature.
PhenylephrineDrug
Phenylephrine, at applicable concentrations based on literature.
NorepinephrineDrug
Norepinephrine, at applicable concentrations based on literature.
OxytocinDrug
Also called pitocin
Oxytocin, at applicable concentrations based on literature.
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | The myometrial samples are bathed in physiological salt solution (PSS) only. |
| Ephedrine | Active comparator | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine. Receives: Drug: Ephedrine |
| Phenylephrine | Active comparator | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine. Receives: Drug: Phenylephrine |
| Norepinephrine | Active comparator | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine. Receives: Drug: Norepinephrine |
| Control + oxytocin | Active comparator | The myometrial samples are bathed in physiological salt solution (PSS) and oxytocin. Receives: Drug: Oxytocin |
| Ephedrine + oxytocin | Active comparator | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine and oxytocin.. Receives: Drug: Ephedrine; Drug: Oxytocin |
| Phenylephrine + oxytocin | Active comparator | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine and oxytocin.. Receives: Drug: Phenylephrine; Drug: Oxytocin |
| Norepinephrine + oxytocin | Active comparator | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine and oxytocin.. Receives: Drug: Norepinephrine; 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 start18 Mar 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
- 96 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
- NCT06285396
- Sponsor's protocol ID
- 24-01
- Status last verified
- Jul 2025
- 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
- Effect of Ephedrine, Phenylepinephrine, and Norepinephrine on Myometrial Contractility in Pregnant People With Type II and Gestational Diabetes During Cesarean Section: An In-vitro Study
- ClinicalTrials.gov ID
- NCT06285396
- Acronym / sponsor ID
- 24-01
- Conditions
- Postpartum Hemorrhage
- Keywords
- oxytocin, type II diabetes, gestational diabetes, uterine contraction
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- 18 Mar 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.
The goal of this study is to learn about how medication that is used to help treat low blood pressure during a Cesarean delivery (CD) can cause changes to the uterine muscle tissue and its ability to contract, in patients with Type II and gestational diabetes.
Spinal anesthesia administered during elective CD has been known to cause hypotension (low blood pressure) as a side effect during the procedure, and is prevented by administration of vasopressors (medication to raise blood pressure) by the anesthesiologist after the delivery of the baby. Vasopressors treat hypotension by interacting with receptors on blood vessels that increase blood pressure, which can also cause changes to uterine contractility. Inadequate uterine contraction after CD can expose mothers to postpartum hemorrhage (PPH), with diabetic patients displaying a 2.5-times higher risk of PPH.
It is important to understand how vasopressor(s) might affect the uterine contractility of women with Type II and gestational diabetes. Since medication to contract the uterus is also routinely administered at delivery, it is important to study the effect of these drugs in combination. The purpose of this study is to compare uterine contractility patterns and receptor distribution in women with type II and gestational diabetic and control term pregnant patients with administration of vasopressors. This will be done using small uterine tissue samples taken from the incision site following CD, which will then be used for experiments in the laboratory.
Detailed description
The global prevalence of diabetes has increased drastically over the past 20 years, with 1.5 million new cases each year. The prevalence of Type II diabetes in women of childbearing age has shown the greatest increase, in the United States alone rising from 33% in 1990-1998 to 70% in 2020. Additionally, the worldwide rate of cesarean delivery (CD) follows a similar trend. CD procedures can be both elective and emergent, with the rate of elective CD increasing by 30% in Canada since 2001. Neuraxial anesthesia administered during elective CD has been known to induce hypotension as a side effect, which is then countered by administering vasopressors such as epinephrine, norepinephrine, and phenylephrine that act on adrenergic alpha and beta receptors on smooth muscle tissue. However, since these receptors are expressed on the smooth muscle layer of the uterus called the myometrium, vasopressors can elicit changes in myometrial contractility. Inadequate myometrial contractility during CD can expose the mother to postpartum hemorrhage (PPH) which is a leading cause of maternal mortality worldwide.
Additionally, diabetic women undergoing CD are often obese (BMI > 30 kg/m2) or have macrosomia (larger than average baby), which are independent risk factors for PPH. However, there is still a 2.5-fold increased risk in PPH in Type II diabetic patients, even when adjusted for diabetic-associated obesity. Type II diabetics undergoing elective CD also display a reduced contractile profile (as previously explored through in-vitro calcium signaling), which may contribute to their increased risk of PPH. Current research on myometrial contractility shows that throughout the gestational period, the adrenergic receptor subtypes on the myometrial tissue may transition to more pro-contractile phenotypes, which may react differently to administered vasopressors and thus affect induced contractility during CD. Oxytocin, a uterotonic, is the standard treatment for preventing PPH administered immediately after delivery.
There is currently no literature on the unique effects of vasopressors to manage hypotension in obstetric patients who are diagnosed with Type II and gestational diabetes. The increased risk of PPH at CD seen in type II and Gestational diabetics mothers may be due to differences in adrenergic receptor distribution, which have different affinities to the vasopressors administered. No studies thus far have directly explored the role of vasopressors on myometrial contractions in this patient population.
As the use of a standardized vasopressor dosage becomes more routine during elective CD, it is important to understand how this will affect the myometrial contractility of women with Type II and gestational diabetes. The investigators hypothesize that administration of vasopressors in full term pregnant women with type II and gestational diabetes will cause decreased myometrial contractility compared to healthy controls, and that the diabetic tissue will possess a different adrenergic receptor subtype profile compared to controls.
Aim 1: Investigate the differences in myometrial contractility of type II and gestational diabetic vs. control term pregnant patients with administration of vasopressors
Aim 2: Determine the expression of adrenergic receptor subtypes on myometrium of term pregnant type II and gestational diabetic patients
Aim 3: Investigate the difference in downstream adrenergic pathways proteins in myometrial of type II and gestational diabetics vs control patients with administration of vasopressors
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –The myometrial samples are bathed in physiological salt solution (PSS) only. |
| Ephedrine | Active comparator | Drug: EphedrineThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine. |
| Phenylephrine | Active comparator | Drug: PhenylephrineThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine. |
| Norepinephrine | Active comparator | Drug: NorepinephrineThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine. |
| Control + oxytocin | Active comparator | Drug: OxytocinThe myometrial samples are bathed in physiological salt solution (PSS) and oxytocin. |
| Ephedrine + oxytocin | Active comparator | Drug: Ephedrine, Drug: OxytocinThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine and oxytocin.. |
| Phenylephrine + oxytocin | Active comparator | Drug: Phenylephrine, Drug: OxytocinThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine and oxytocin.. |
| Norepinephrine + oxytocin | Active comparator | Drug: Norepinephrine, Drug: OxytocinThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine and oxytocin.. |
Who may qualify
- Ages
- 19 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Patients who have given consent to participate in the study
- Patients with gestational age 37-41 weeks
- Patients previously diagnosed with either Type II or Gestational diabetes. For the healthy control group, no previous diagnosis is required for inclusion
- Patients of 19-45 years
- Patients of normal BMI (18-30 BMI) for the healthy control group only
Key exclusion criteria (8 listed)
- Patients who refuse to give written informed consent
- Patients who require general anesthesia
- Patients in labor and those receiving oxytocin for induction of labor
- Emergency caesarean delivery in labor
- Patients who have had previous uterine surgery involving myometrial dissection or >1 previous caesarean delivery
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 |
|---|---|---|
| EphedrineEphedrine in solution, at applicable concentrations based on literature. | Drug | Ephedrine, Ephedrine + oxytocin |
| PhenylephrinePhenylephrine, at applicable concentrations based on literature. | Drug | Phenylephrine, Phenylephrine + oxytocin |
| NorepinephrineNorepinephrine, at applicable concentrations based on literature. | Drug | Norepinephrine, Norepinephrine + oxytocin |
| OxytocinAlso: pitocinOxytocin, at applicable concentrations based on literature. | Drug | Control + oxytocin, Ephedrine + oxytocin, Norepinephrine + oxytocin, Phenylephrine + oxytocin |
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
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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 Ephedrine, Phenylephrine and Norepinephrine 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 9 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. 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.