Postpartum HemorrhageNCT03852797
Spontaneous and Oxytocin-induced Contractility After Exposure to Intravenous Anesthetic Agents: an In-vitro Study in Human Myometrium
A study testing Oxytocin, Ketamine and Propofol in people with Postpartum Hemorrhage, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site in Canada.
Trial summary
Poor uterine tone after the birth of a baby may cause serious bleeding (called postpartum hemorrhage or PPH). This is a major cause of maternal death worldwide. In the developed world the cesarean section rate is increasing. There are two modalities for anesthesia for cesarean section; general and regional (eg. Read more about this study
- Who is it for?
- Ages 19 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postpartum Hemorrhage
- What is being tested?
- Oxytocin, Ketamine and Propofol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteCanada
- Study dates
- 28 Mar 2019to 19 Jan 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 19 to 50 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 19-50 years
- Non-laboring patients, not exposed to exogenous oxytocin
- Patients requiring primary Cesarean section or first repeat Cesarean section
- Patients undergoing Cesarean section under spinal anesthesia
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 section
- 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 sulphate.
- Patients who have been exposed to oxytocin prior or during the cesarean section.
Trial locations and contacts
1 site in 1 country.
About this study
Poor uterine tone after the birth of a baby may cause serious bleeding (called postpartum hemorrhage or PPH). This is a major cause of maternal death worldwide. In the developed world the cesarean section rate is increasing. There are two modalities for anesthesia for cesarean section; general and regional (eg. spinal anesthetic). General anesthesia has been associated with increased blood loss compared to regional and the reasons for this may be multifactorial. Some of the anesthesia gases have been studied and there is laboratory evidence to suggest that these gases may reduce the tone of the uterus and therefore cause increased blood loss due to poor uterine tone. To date there has been little study on the intravenous anesthesia agents. These agents are usually administered to anaesthetise the patient at the start of surgery (induction of anesthesia), however they can also be used instead of the gases to keep the patient asleep using a 'total intravenous anesthesia' technique. Laboratory work in rats has suggested that high doses of these intravenous drugs might reduce uterine tone, thus increasing the risk of blood loss. Interestingly, at low doses one of these drugs (ketamine) may actually increase uterine tone. Only one of these drugs has been studied in human uterine tissue. The investigators plan to compare three anaesthesia induction agents on human uterine tissue under physiological conditions in the laboratory.
This study will be the first to compare these three drugs on human tissue. The investigators plan to determine the impact of these drugs on spontaneous uterine contractility and also contractilty induced by oxytocin, which is the drug most commonly administered to help contract the uterus after birth. This is important as it will help inform anesthesiologists as to the best drug to use depending on the clinical circumstance.
The investigators hypothesize that the intravenous induction agents will cause a dose dependent decrease in spontaneous uterine contractility, similar to what has been described in the rat model. The investigators also expect that exposure to high concentrations of intravenous anesthesia induction agents will cause a blunted contractile response to oxytocin.
Read the detailed description
There is an increasing need to fully understand the mechanisms that contribute to the higher blood loss after general anesthesia during cesarean section therefore it is important the investigators identify all pharmacological contributors to poor uterine tone. Furthermore, anesthesiologists are increasingly called upon to care for women undergoing a range of in-utero fetal surgeries which require a careful balanced anesthetic and strict control of uterine tone.
This will be the first study that compares the three commonly used intravenous anesthesia agents on human myometrium: ketamine, etomidate and propofol. This study is required to allow doctors make informed decisions about which anesthesia agent is most suitable to manage their patient depending on clinical circumstances.
The specific objective of this project is to investigate the pharmacological dose-response profiles of different anesthesia induction agents by in-vitro isometric tension measurements of contractions in gravid human myometrium. The investigators will study both spontaneous and oxytocin induced contractility.
- Conditions
- Postpartum Hemorrhage
- Keywords
- uterine contraction, oxytocin, ketamine, propofol, etomidate
- 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 solution, 20nM concentration
KetamineDrug
Also called ketamine HCl
Ketamine in solution, 10-4M to 10-7M
PropofolDrug
Propofol in solution, 10-4M to 10-7M
EtomidateDrug
Etomidate in solution, 10-4M to 10-7M
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Active comparator | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of ketamine (from 10 -7M to 10 -4M) Receives: Drug: Ketamine |
| Ketamine + oytocin | Active comparator | The myometrial samples are bathed in an oxytocin solution (20nM) with increasing concentrations of ketamine (from 10 -7M to 10 -4M) Receives: Drug: Oxytocin; Drug: Ketamine |
| Propofol | Active comparator | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of propofol (from 10 -7M to 10 -4M) Receives: Drug: Propofol |
| Propofol + oytocin | Active comparator | The myometrial samples are bathed in an oxytocin solution (20nM) with increasing concentrations of propofol (from 10 -7M to 10 -4M) Receives: Drug: Oxytocin; Drug: Propofol |
| Etomidate | Active comparator | The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of etomidate (from 10 -7M to 10 -4M) Receives: Drug: Etomidate |
| Etomidate + oytocin | Active comparator | The myometrial samples are bathed in an oxytocin solution (20nM) with increasing concentrations of etomidate (from 10 -7M to 10 -4M) Receives: Drug: Oxytocin; Drug: Etomidate |
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 posted25 Feb 2019
- Study start28 Mar 2019
- Primary completion19 Jan 2022
- Study completion19 Jan 2022
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 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
- NCT03852797
- Sponsor's protocol ID
- 19-01
- Status last verified
- Oct 2022
- First submitted
- 21 Feb 2019
- Last updated
- 25 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Spontaneous and Oxytocin-induced Contractility After Exposure to Intravenous Anesthetic Agents: an In-vitro Study in Human Myometrium
- ClinicalTrials.gov ID
- NCT03852797
- Acronym / sponsor ID
- 19-01
- Conditions
- Postpartum Hemorrhage
- Keywords
- uterine contraction, oxytocin, ketamine, propofol, etomidate
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- 28 Mar 2019 (actual)
- Primary completion
- 19 Jan 2022 (actual)
- Study completion
- 19 Jan 2022 (actual)
- First posted
- 25 Feb 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.
Poor uterine tone after the birth of a baby may cause serious bleeding (called postpartum hemorrhage or PPH). This is a major cause of maternal death worldwide. In the developed world the cesarean section rate is increasing. There are two modalities for anesthesia for cesarean section; general and regional (eg. spinal anesthetic). General anesthesia has been associated with increased blood loss compared to regional and the reasons for this may be multifactorial. Some of the anesthesia gases have been studied and there is laboratory evidence to suggest that these gases may reduce the tone of the uterus and therefore cause increased blood loss due to poor uterine tone. To date there has been little study on the intravenous anesthesia agents. These agents are usually administered to anaesthetise the patient at the start of surgery (induction of anesthesia), however they can also be used instead of the gases to keep the patient asleep using a 'total intravenous anesthesia' technique. Laboratory work in rats has suggested that high doses of these intravenous drugs might reduce uterine tone, thus increasing the risk of blood loss. Interestingly, at low doses one of these drugs (ketamine) may actually increase uterine tone. Only one of these drugs has been studied in human uterine tissue. The investigators plan to compare three anaesthesia induction agents on human uterine tissue under physiological conditions in the laboratory.
This study will be the first to compare these three drugs on human tissue. The investigators plan to determine the impact of these drugs on spontaneous uterine contractility and also contractilty induced by oxytocin, which is the drug most commonly administered to help contract the uterus after birth. This is important as it will help inform anesthesiologists as to the best drug to use depending on the clinical circumstance.
The investigators hypothesize that the intravenous induction agents will cause a dose dependent decrease in spontaneous uterine contractility, similar to what has been described in the rat model. The investigators also expect that exposure to high concentrations of intravenous anesthesia induction agents will cause a blunted contractile response to oxytocin.
Detailed description
There is an increasing need to fully understand the mechanisms that contribute to the higher blood loss after general anesthesia during cesarean section therefore it is important the investigators identify all pharmacological contributors to poor uterine tone. Furthermore, anesthesiologists are increasingly called upon to care for women undergoing a range of in-utero fetal surgeries which require a careful balanced anesthetic and strict control of uterine tone.
This will be the first study that compares the three commonly used intravenous anesthesia agents on human myometrium: ketamine, etomidate and propofol. This study is required to allow doctors make informed decisions about which anesthesia agent is most suitable to manage their patient depending on clinical circumstances.
The specific objective of this project is to investigate the pharmacological dose-response profiles of different anesthesia induction agents by in-vitro isometric tension measurements of contractions in gravid human myometrium. The investigators will study both spontaneous and oxytocin induced contractility.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Active comparator | Drug: KetamineThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of ketamine (from 10 -7M to 10 -4M) |
| Ketamine + oytocin | Active comparator | Drug: Oxytocin, Drug: KetamineThe myometrial samples are bathed in an oxytocin solution (20nM) with increasing concentrations of ketamine (from 10 -7M to 10 -4M) |
| Propofol | Active comparator | Drug: PropofolThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of propofol (from 10 -7M to 10 -4M) |
| Propofol + oytocin | Active comparator | Drug: Oxytocin, Drug: PropofolThe myometrial samples are bathed in an oxytocin solution (20nM) with increasing concentrations of propofol (from 10 -7M to 10 -4M) |
| Etomidate | Active comparator | Drug: EtomidateThe myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of etomidate (from 10 -7M to 10 -4M) |
| Etomidate + oytocin | Active comparator | Drug: Oxytocin, Drug: EtomidateThe myometrial samples are bathed in an oxytocin solution (20nM) with increasing concentrations of etomidate (from 10 -7M to 10 -4M) |
Who may qualify
- Ages
- 19 to 50 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 19-50 years
- Non-laboring patients, not exposed to exogenous oxytocin
- Patients requiring primary Cesarean section or first repeat Cesarean section
Key exclusion criteria (7 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 section
- 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 solution, 20nM concentration | Drug | Etomidate + oytocin, Ketamine + oytocin, Propofol + oytocin |
| KetamineAlso: ketamine HClKetamine in solution, 10-4M to 10-7M | Drug | Ketamine, Ketamine + oytocin |
| PropofolPropofol in solution, 10-4M to 10-7M | Drug | Propofol, Propofol + oytocin |
| EtomidateEtomidate in solution, 10-4M to 10-7M | Drug | Etomidate, Etomidate + oytocin |
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
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 25 Oct 2022.
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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, Ketamine and Propofol 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 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: finished, as of the sponsor's last update on 25 Oct 2022. 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: 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 25 Oct 2022.