Postpartum HemorrhageNCT02647268
Effect of Magnesium Sulphate Pre-exposure on Oxytocin-induced Contractility in Desensitized Human Myometrium - an in Vitro Study
A study testing Oxytocin and Magnesium Sulphate in people with Postpartum Hemorrhage, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site in Canada.
Trial summary
Postpartum hemorrhage (PPH) is the loss of more than 500ml of blood within 24 hours after delivery. It is a major cause of maternal morbidity and mortality across the globe. Oxytocin is a naturally-occurring hormone that causes the uterus to contract, thereby causing labor. 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 Magnesium Sulphate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2016to Apr 2017
- 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 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 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 with medical/pregnancy related conditions, such as diabetes, preeclampsia and essential hypertension
Trial locations and contacts
1 site in 1 country.
About this study
Postpartum hemorrhage (PPH) is the loss of more than 500ml of blood within 24 hours after delivery. It is a major cause of maternal morbidity and mortality across the globe.
Oxytocin is a naturally-occurring hormone that causes the uterus to contract, thereby causing labor. A synthetic form of oxytocin is used in obstetric medicine in the same way. It causes the uterus to contract by acting at the oxytocin receptor (OTR). It is used for both the prevention and the treatment of PPH. By causing the uterus to contract, it constricts the blood vessels within it, thus reducing bleeding.
Read more
Oxytocin is also used to augment labor in women with slow labor progression. Desensitization of the OTR after prolonged exposure to oxytocin occurs, leading to reduced contractions of the uterus with the same doses of oxytocin. This has been demonstrated in previous studies done by the investigators. The resultant need for a higher oxytocin dose to cause adequate uterine contraction has also been demonstrated in laboring women having received oxytocin for labor augmentation.
Magnesium sulphate (MgSO4) is widely used within obstetric medicine. It is used for seizure prevention and treatment in preeclampsia and eclampsia, and is used for fetal neuroprotection in preterm labor, to reduce the risk of cerebral palsy. It is well-known to have a relaxant effect on uterine muscle, and as such, has been used as a tocolytic agent in preterm labour to prevent premature contractions and premature delivery. The effect of MgSO4 on contractions in oxytocin pre-treated myometrium has not been fully elucidated with human lab studies. There are suggestions it may lead to increased oxytocin requirements or increased postpartum hemorrhage (PPH) in preeclamptic patients. This bears significance in the preeclamptic and eclamptic populations who are likely to be receiving MgSO4 in combination with oxytocin.
The investigators hypothesize that MgSO4 will reduce uterine contractions in oxytocin pre-treated myometrium, as well as untreated myometrium, and higher oxytocin doses will be needed to produce equivalent contractions. This will help us to better understand the implications of the use of these drugs together in the clinical setting.
Read the detailed description
MgSO4 is known to cause relaxation of uterine muscle in the doses used for preeclampsia and eclampsia and fetal neuroprotection. In these clinical settings, after delivery, oxytocin is often given to prevent or treat PPH. There is evidence that patients with preeclampsia already have a higher risk of PPH than non-preeclamptic patients. In the presence of the effects of MgSO4 treatment on the uterus, PPH could be worse in theory. If patients have had oxytocin-augmented labor, then the desensitization effect on the uterus also comes into play. Performing this study in vitro will allow us to assess the effects on the uterine muscle of MgSO4 in oxytocin-desensitized tissue samples.
Scientific evidence on pregnancy outcomes in these patients is timely and important. A study of myometrial contractility under controlled conditions is likely to provide us with information on the interactions between oxytocin and MgSO4 that occurs in many clinical scenarios, eliminating any confounders that could be encountered in clinical settings. The investigators hope to determine the myometrial contraction patterns induced by oxytocin in the presence of MgSO4, including in myometrial specimens pre-treated with oxytocin plus MgSO4, to mimic the clinical scenarios in preeclampsia and fetal neuroprotection. This will expand the depth of our understanding of the desensitization phenomenon, and could provide valuable insight into the mechanism responsible for PPH in these patient populations. This study will form a basis for future modifications in oxytocin augmentation regimens and pharmacotherapy for control of uterine atony and PPH in these patient populations being simultaneously treated with MgSO4.
- Conditions
- Postpartum Hemorrhage
- Being tested
- Oxytocin, Magnesium Sulphate
- Keywords
- Uterine contraction, Oxytocin, Magnesium sulphate
- 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, 10-5M solution
Magnesium SulphateDrug
Magnesium sulphate, 3.5mM solution
| Study group | Role | What they receive |
|---|---|---|
| Control (no oxytocin) pretreatment | No intervention | The myometrial samples are bathed in physiological saline solution (PSS). |
| Magnesium Sulphate | Active comparator | The myometrial samples are bathed in a 3.5mM magnesium sulphate solution. Receives: Drug: Magnesium Sulphate |
| Magnesium Sulphate + oxytocin | Active comparator | The myometrial samples are bathed in a 3.5mM magnesium sulphate plus 10-5M oxytocin solution. Receives: Drug: Oxytocin; Drug: Magnesium Sulphate |
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: 2 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: 2 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: 2 hours
Integrated area under response curve (AUC)
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2016 (estimated)
- Study startJan 2016
- Primary completionApr 2017
- Study completionApr 2017
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
- 26 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
- NCT02647268
- Sponsor's protocol ID
- 16-01
- Status last verified
- Jul 2017
- First submitted
- 4 Jan 2016
- Last updated
- 17 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Onwochei DN, Carvalho JCA, Luca A, Kingdom J, Balki M. Effect of magnesium sulfate on oxytocin-induced contractility in human myometrium: an in vitro study. Can J Anaesth. 2017 Jul;64(7):744-753. doi: 10.1007/s12630-017-0867-3. Epub 2017 Mar 30.
PubMed 28361390
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Magnesium Sulphate Pre-exposure on Oxytocin-induced Contractility in Desensitized Human Myometrium - an in Vitro Study
- ClinicalTrials.gov ID
- NCT02647268
- Acronym / sponsor ID
- 16-01
- Conditions
- Postpartum Hemorrhage
- Keywords
- Uterine contraction, Oxytocin, Magnesium sulphate
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 6 Jan 2016 (estimated)
- 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.
Postpartum hemorrhage (PPH) is the loss of more than 500ml of blood within 24 hours after delivery. It is a major cause of maternal morbidity and mortality across the globe.
Oxytocin is a naturally-occurring hormone that causes the uterus to contract, thereby causing labor. A synthetic form of oxytocin is used in obstetric medicine in the same way. It causes the uterus to contract by acting at the oxytocin receptor (OTR). It is used for both the prevention and the treatment of PPH. By causing the uterus to contract, it constricts the blood vessels within it, thus reducing bleeding.
Oxytocin is also used to augment labor in women with slow labor progression. Desensitization of the OTR after prolonged exposure to oxytocin occurs, leading to reduced contractions of the uterus with the same doses of oxytocin. This has been demonstrated in previous studies done by the investigators. The resultant need for a higher oxytocin dose to cause adequate uterine contraction has also been demonstrated in laboring women having received oxytocin for labor augmentation.
Magnesium sulphate (MgSO4) is widely used within obstetric medicine. It is used for seizure prevention and treatment in preeclampsia and eclampsia, and is used for fetal neuroprotection in preterm labor, to reduce the risk of cerebral palsy. It is well-known to have a relaxant effect on uterine muscle, and as such, has been used as a tocolytic agent in preterm labour to prevent premature contractions and premature delivery. The effect of MgSO4 on contractions in oxytocin pre-treated myometrium has not been fully elucidated with human lab studies. There are suggestions it may lead to increased oxytocin requirements or increased postpartum hemorrhage (PPH) in preeclamptic patients. This bears significance in the preeclamptic and eclamptic populations who are likely to be receiving MgSO4 in combination with oxytocin.
The investigators hypothesize that MgSO4 will reduce uterine contractions in oxytocin pre-treated myometrium, as well as untreated myometrium, and higher oxytocin doses will be needed to produce equivalent contractions. This will help us to better understand the implications of the use of these drugs together in the clinical setting.
Detailed description
MgSO4 is known to cause relaxation of uterine muscle in the doses used for preeclampsia and eclampsia and fetal neuroprotection. In these clinical settings, after delivery, oxytocin is often given to prevent or treat PPH. There is evidence that patients with preeclampsia already have a higher risk of PPH than non-preeclamptic patients. In the presence of the effects of MgSO4 treatment on the uterus, PPH could be worse in theory. If patients have had oxytocin-augmented labor, then the desensitization effect on the uterus also comes into play. Performing this study in vitro will allow us to assess the effects on the uterine muscle of MgSO4 in oxytocin-desensitized tissue samples.
Scientific evidence on pregnancy outcomes in these patients is timely and important. A study of myometrial contractility under controlled conditions is likely to provide us with information on the interactions between oxytocin and MgSO4 that occurs in many clinical scenarios, eliminating any confounders that could be encountered in clinical settings. The investigators hope to determine the myometrial contraction patterns induced by oxytocin in the presence of MgSO4, including in myometrial specimens pre-treated with oxytocin plus MgSO4, to mimic the clinical scenarios in preeclampsia and fetal neuroprotection. This will expand the depth of our understanding of the desensitization phenomenon, and could provide valuable insight into the mechanism responsible for PPH in these patient populations. This study will form a basis for future modifications in oxytocin augmentation regimens and pharmacotherapy for control of uterine atony and PPH in these patient populations being simultaneously treated with MgSO4.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control (no oxytocin) pretreatment | No intervention | –The myometrial samples are bathed in physiological saline solution (PSS). |
| Magnesium Sulphate | Active comparator | Drug: Magnesium SulphateThe myometrial samples are bathed in a 3.5mM magnesium sulphate solution. |
| Magnesium Sulphate + oxytocin | Active comparator | Drug: Oxytocin, Drug: Magnesium SulphateThe myometrial samples are bathed in a 3.5mM magnesium sulphate plus 10-5M oxytocin solution. |
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 under spinal anesthesia
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, 10-5M solution | Drug | Magnesium Sulphate + oxytocin |
| Magnesium SulphateMagnesium sulphate, 3.5mM solution | Drug | Magnesium Sulphate, Magnesium Sulphate + oxytocin |
Primary outcome
Motility Index
Time frame: 2 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: 2 hours
Frequency of contraction
Time frame: 2 hours
Integrated area under response curve (AUC)
Time frame: 2 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 17 Jul 2017.
- Derived from this study: PubMed 28361390Onwochei DN, Carvalho JCA, Luca A, Kingdom J, Balki M. Effect of magnesium sulfate on oxytocin-induced contractility in human myometrium: an in vitro study. Can J Anaesth. 2017 Jul;64(7):744-753. doi: 10.1007/s12630-017-0867-3. Epub 2017 Mar 30.
- Individual participant dataSharing planned: No
Related trials for Postpartum Hemorrhage
Not yet recruiting
Comparison of Effect of Two Different Doses of Intravenous Oxytocin on Patients Undergoing Elective Cesarean Section
Postpartum Hemorrhage, Uterine Atony
RecruitingPhase 3
Tranexamic Acid to Prevent Heavy Bleeding After Childbirth in Women at Higher Risk
Postpartum Hemorrhage
Not yet recruitingObservational study
Measured Versus Hemoglobin-Calculated Postpartum Blood Loss in Waterbirth
Postpartum Hemorrhage, Waterbirth
RecruitingObservational study
Long Term Outcome After Use of Vacuum-induced Tamponade for Postpartum Hemorrhage
Postpartum Hemorrhage, Treatment Outcome
RecruitingPhase 2
Prevention of Postpartum Hemorrhage With Tranexamic Acid
Post Partum Hemorrhage
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 Magnesium Sulphate 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 17 Jul 2017. 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: 2 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 NCT02647268, 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 17 Jul 2017.