HypotensionNCT04053478
Effects of Ephedrine, Phenylephrine, Norepinephrine and Vasopressin on Contractility of Human Myometrium and Umbilical Vessels: An In-vitro Study
A study testing Ephedrine, Phenylephrine and Norepinephrine in people with Hypotension, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site in Canada.
Trial summary
Hypotension is one of the most common adverse effects of spinal anesthesia for cesarean deliveries, affecting as many as 55-90% of mothers. Hypotension during cesarean deliveries can have detrimental effects on the mother and neonate. Read more about this study
- Who is it for?
- Ages 19 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Hypotension
- What is being tested?
- Ephedrine, Phenylephrine and Norepinephrine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 1 siteCanada
- Study dates
- 8 Jul 2019to 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 40 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
- Patients of 19-40 years
- 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 or >1 previous caesarean delivery
- Patients with any condition predisposing to uterine atony
- Patients on medications that could affect myometrial contractility, such as insulin, nifedipine, labetolol or magnesium sulfate.
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
Alice Luca, MSc
About this study
Hypotension is one of the most common adverse effects of spinal anesthesia for cesarean deliveries, affecting as many as 55-90% of mothers. Hypotension during cesarean deliveries can have detrimental effects on the mother and neonate. Various vasopressors, such as ephedrine, phenylephrine and more recently norepinephrine, have been used for the prevention and treatment of hypotension at cesarean deliveries.
Ephedrine was historically considered as the gold standard vasopressor for the management of hypotension during cesarean deliveries. This was based on studies in animal models that showed preserved uteroplacental circulation with ephedrine and not with phenylephrine. However, multiple studies in the past several decades have shown that phenylephrine compared with ephedrine results in a more favorable fetal acid-base status. Consequently, the use of phenylephrine for blood pressure management during cesarean deliveries increased. Recently, norepinephrine was introduced in the obstetrical practice for the management of hypotension at cesarean deliveries, due to its ability to maintain maternal cardiac output better than phenylephrine.
Read more
Studies have also investigated the use of vasopressin to limit hypotension during CD. There have been case reports of successful vasopressin usage to treat post-spinal hypotension after CD in patients with advanced idiopathic pulmonary arterial hypertension as well as severe mitral stenosis with pulmonary hypertension. Its effect was associated with hemodynamic stability without evidence of harm to the mother or child. However, much controversy still exists surrounding the choice of vasopressor in the obstetric population, in large part due to their varying efficacies, and maternal and fetal effects.
Vasopressors used for the treatment of hypotension during cesarean deliveries can have significant direct or indirect effects on the perfusion of uteroplacental and umbilical vessels. Reduction of uteroplacental perfusion and constriction of umbilical vessels can result in fetal acidosis, however, the mechanisms for these effects are unclear. The investigators hypothesize that ephedrine, phenylephrine and norepinephrine and vasopressin have variable effects on the contractility of pregnant myometrium and umbilical arteries due to their variable actions on adrenergic alpha (α) and beta (β) receptors, as well as vasopressin1 and vasopressin2 receptors located in these tissues.
Read the detailed description
One of the major concerns addressed in the literature is the risk of fetal acidosis related to the use of vasopressors, which varies according to the type of drug used. Since severe fetal acidosis is associated with a two- and four-fold increase in neonatal morbidity and mortality, respectively, it is important to understand the mechanism by which these medications may contribute to fetal acidosis.
It is well known that reduced uteroplacental blood flow can result in impaired fetal oxygenation and fetal acidosis. This can occur indirectly via compression of vessels due to myometrial contractions or directly by vasoactive effects on umbilical vessels. So far, no studies have directly explored the role of the aforementioned vasopressors on myometrial contractions and umbilical vessel vasoconstriction. An in-vitro approach in isolated tissues will eliminate many clinical confounding variables, allowing direct comparison of the drugs in a controlled environment, and providing insight into the contractile mechanisms responsible for their neonatal effects.
There is currently no consensus as to which vasopressor is best for the management of hypotension in obstetric patients and the mitigation of fetal acidosis. A survey of the members of the Society of Obstetric Anesthesia and Perinatology suggested significant variation in the practice of vasopressor use during cesarean deliveries. The evidence from animal studies contradicts the effects seen in human studies. This is possibly related to species differences in adrenergic receptor distribution, affinity to vasopressors, or placental transfer of vasopressors. It is well known that reduced uteroplacental blood flow can result in impaired fetal oxygenation and fetal acidosis. This can occur indirectly via compression of vessels due to myometrial contractions or directly by vasoactive effects on umbilical arteries. However, none of the studies so far have directly explored the role of the aforementioned vasopressors on myometrial contractions and umbilical artery vasoconstriction. An in-vitro approach in isolated tissues will eliminate many clinical confounding variables, allowing direct comparison of the drugs in a controlled environment, and providing insight into the contractile mechanisms responsible for their neonatal effects.
- Conditions
- Hypotension
- Being tested
- Ephedrine, Phenylephrine, Norepinephrine, Vasopressin
- Keywords
- vasopressor, ephedrine, phenylephrine, norepinephrine, umbilical arteries, uterine contraction, fetal acidosis, vasopressin
- Medical subject headings
- Hypotension, Diabetes Insipidus
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
VasopressinDrug
Vasopressin, at applicable concentrations based on literature
| Study group | Role | What they receive |
|---|---|---|
| Myometrium + Ephedrine | Experimental | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine Receives: Drug: Ephedrine |
| Myometrium + Phenylephrine | Experimental | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine Receives: Drug: Phenylephrine |
| Myometrium + Norepinephrine | Experimental | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine Receives: Drug: Norepinephrine |
| Myometrium + Vasopressin | Experimental | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of vasopressin Receives: Drug: Vasopressin |
| Umbilical artery + Ephedrine | Experimental | The umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine Receives: Drug: Ephedrine |
| Umbilical artery + Phenylephrine | Experimental | The umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine Receives: Drug: Phenylephrine |
| Umbilical artery + Norepinephrine | Experimental | The umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine Receives: Drug: Norepinephrine |
| Umbilical artery + Vasopressin | Experimental | The umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of vasopressin Receives: Drug: Vasopressin |
| Umbilical vein + Ephedrine | Experimental | The umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine Receives: Drug: Ephedrine |
| Umbilical vein + Phenylephrine | Experimental | The umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine Receives: Drug: Phenylephrine |
| Umbilical vein + Norepinephrine | Experimental | The umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine Receives: Drug: Norepinephrine |
| Umbilical vein + Vasopressin | Experimental | The umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of vasopressin Receives: Drug: Vasopressin |
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 and umbilical vessel contractions, measured in grams (g). The analysis is undertaken by attaching myometrial strips and umbilical vessel rings 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) and umbilical vessel rings over 10 minutes, spontaneously and in response to an agonist.
The analysis is undertaken by attaching myometrial strips and umbilical vessel rings 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 posted12 Aug 2019
- Study start8 Jul 2019
- 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 HypotensionStudies 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
- 144 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
- NCT04053478
- Sponsor's protocol ID
- 19-04
- Status last verified
- Mar 2026
- First submitted
- 8 Aug 2019
- 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
- Effects of Ephedrine, Phenylephrine, Norepinephrine and Vasopressin on Contractility of Human Myometrium and Umbilical Vessels: An In-vitro Study
- ClinicalTrials.gov ID
- NCT04053478
- Acronym / sponsor ID
- 19-04
- Conditions
- Hypotension
- Keywords
- vasopressor, ephedrine, phenylephrine, norepinephrine, umbilical arteries, uterine contraction, fetal acidosis, vasopressin
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- 8 Jul 2019 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 12 Aug 2019 (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.
Hypotension is one of the most common adverse effects of spinal anesthesia for cesarean deliveries, affecting as many as 55-90% of mothers. Hypotension during cesarean deliveries can have detrimental effects on the mother and neonate. Various vasopressors, such as ephedrine, phenylephrine and more recently norepinephrine, have been used for the prevention and treatment of hypotension at cesarean deliveries.
Ephedrine was historically considered as the gold standard vasopressor for the management of hypotension during cesarean deliveries. This was based on studies in animal models that showed preserved uteroplacental circulation with ephedrine and not with phenylephrine. However, multiple studies in the past several decades have shown that phenylephrine compared with ephedrine results in a more favorable fetal acid-base status. Consequently, the use of phenylephrine for blood pressure management during cesarean deliveries increased. Recently, norepinephrine was introduced in the obstetrical practice for the management of hypotension at cesarean deliveries, due to its ability to maintain maternal cardiac output better than phenylephrine.
Studies have also investigated the use of vasopressin to limit hypotension during CD. There have been case reports of successful vasopressin usage to treat post-spinal hypotension after CD in patients with advanced idiopathic pulmonary arterial hypertension as well as severe mitral stenosis with pulmonary hypertension. Its effect was associated with hemodynamic stability without evidence of harm to the mother or child. However, much controversy still exists surrounding the choice of vasopressor in the obstetric population, in large part due to their varying efficacies, and maternal and fetal effects.
Vasopressors used for the treatment of hypotension during cesarean deliveries can have significant direct or indirect effects on the perfusion of uteroplacental and umbilical vessels. Reduction of uteroplacental perfusion and constriction of umbilical vessels can result in fetal acidosis, however, the mechanisms for these effects are unclear. The investigators hypothesize that ephedrine, phenylephrine and norepinephrine and vasopressin have variable effects on the contractility of pregnant myometrium and umbilical arteries due to their variable actions on adrenergic alpha (α) and beta (β) receptors, as well as vasopressin1 and vasopressin2 receptors located in these tissues.
Detailed description
One of the major concerns addressed in the literature is the risk of fetal acidosis related to the use of vasopressors, which varies according to the type of drug used. Since severe fetal acidosis is associated with a two- and four-fold increase in neonatal morbidity and mortality, respectively, it is important to understand the mechanism by which these medications may contribute to fetal acidosis.
It is well known that reduced uteroplacental blood flow can result in impaired fetal oxygenation and fetal acidosis. This can occur indirectly via compression of vessels due to myometrial contractions or directly by vasoactive effects on umbilical vessels. So far, no studies have directly explored the role of the aforementioned vasopressors on myometrial contractions and umbilical vessel vasoconstriction. An in-vitro approach in isolated tissues will eliminate many clinical confounding variables, allowing direct comparison of the drugs in a controlled environment, and providing insight into the contractile mechanisms responsible for their neonatal effects.
There is currently no consensus as to which vasopressor is best for the management of hypotension in obstetric patients and the mitigation of fetal acidosis. A survey of the members of the Society of Obstetric Anesthesia and Perinatology suggested significant variation in the practice of vasopressor use during cesarean deliveries. The evidence from animal studies contradicts the effects seen in human studies. This is possibly related to species differences in adrenergic receptor distribution, affinity to vasopressors, or placental transfer of vasopressors. It is well known that reduced uteroplacental blood flow can result in impaired fetal oxygenation and fetal acidosis. This can occur indirectly via compression of vessels due to myometrial contractions or directly by vasoactive effects on umbilical arteries. However, none of the studies so far have directly explored the role of the aforementioned vasopressors on myometrial contractions and umbilical artery vasoconstriction. An in-vitro approach in isolated tissues will eliminate many clinical confounding variables, allowing direct comparison of the drugs in a controlled environment, and providing insight into the contractile mechanisms responsible for their neonatal effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Myometrium + Ephedrine | Experimental | Drug: EphedrineThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine |
| Myometrium + Phenylephrine | Experimental | Drug: PhenylephrineThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine |
| Myometrium + Norepinephrine | Experimental | Drug: NorepinephrineThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine |
| Myometrium + Vasopressin | Experimental | Drug: VasopressinThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of vasopressin |
| Umbilical artery + Ephedrine | Experimental | Drug: EphedrineThe umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine |
| Umbilical artery + Phenylephrine | Experimental | Drug: PhenylephrineThe umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine |
| Umbilical artery + Norepinephrine | Experimental | Drug: NorepinephrineThe umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine |
| Umbilical artery + Vasopressin | Experimental | Drug: VasopressinThe umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of vasopressin |
| Umbilical vein + Ephedrine | Experimental | Drug: EphedrineThe umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine |
| Umbilical vein + Phenylephrine | Experimental | Drug: PhenylephrineThe umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine |
| Umbilical vein + Norepinephrine | Experimental | Drug: NorepinephrineThe umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine |
| Umbilical vein + Vasopressin | Experimental | Drug: VasopressinThe umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of vasopressin |
Who may qualify
- Ages
- 19 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Patients who give written consent to participate in this study
- Patients with gestational age 37-41 weeks
- Patients of 19-40 years
- Non-laboring patients, not exposed to exogenous oxytocin
- Patients requiring elective primary or first repeat caesarean delivery
Key exclusion criteria (7 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 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 | Myometrium + Ephedrine, Umbilical artery + Ephedrine, Umbilical vein + Ephedrine |
| PhenylephrinePhenylephrine, at applicable concentrations based on literature | Drug | Myometrium + Phenylephrine, Umbilical artery + Phenylephrine, Umbilical vein + Phenylephrine |
| NorepinephrineNorepinephrine, at applicable concentrations based on literature | Drug | Myometrium + Norepinephrine, Umbilical artery + Norepinephrine, Umbilical vein + Norepinephrine |
| VasopressinVasopressin, at applicable concentrations based on literature | Drug | Myometrium + Vasopressin, Umbilical artery + Vasopressin, Umbilical vein + Vasopressin |
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 Hypotension, 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 6 inclusion and 7 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.