Postpartum HemorrhageNCT02274454
Investigating the Effect of Extracellular Calcium on Oxytocin-induced Human Myometrial Contractility In-vitro
A study testing Oxytocin and Calcium 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 a leading cause of maternal morbidity and mortality worldwide and is caused most commonly by poor uterine muscle tone after delivery. The first line agent used in the prevention and treatment of PPH is oxytocin, which acts by binding with the oxytocin receptor (OTR) found on myometrial… 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 Calcium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2014to Mar 2015
- 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 CD or first repeat CD
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 CD
- 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 CD in labor
- Patients on medications that could affect myometrial contractility, such as nifedipine, labetolol or magnesium sulphate.
Trial locations and contacts
1 site in 1 country.
About this study
Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide and is caused most commonly by poor uterine muscle tone after delivery. The first line agent used in the prevention and treatment of PPH is oxytocin, which acts by binding with the oxytocin receptor (OTR) found on myometrial cells to cause uterine contraction. It does this by increasing levels of calcium within the myometrial cell, which promotes contraction. Women who require augmentation of labor with intravenous oxytocin because of inadequate labor progression have been shown to be at increased risk of PPH. In-vitro human myometrial models have shown that following prolonged exposure to oxytocin there is desensitization of the myometrium resulting in a significant reduction in contractility upon delivery of further oxytocin.
Optimal levels of calcium are very important for contraction of the uterine muscle. Too little calcium results in a reduced contraction. Too much calcium may result in either stronger contractions, or even possibly relaxation of the muscle and therefore a reduced contraction. The investigators currently do not know the effects of calcium on the desensitized uterine muscle.
The investigators hypothesize that myometrial contractility following desensitization of the myometrium would be reduced in myometrial samples exposed to low calcium, when compared to normal calcium or high calcium exposure. These results will help in establishing whether myometrial contraction can be augmented by increasing calcium levels within the body, or by optimizing normal physiological calcium levels, in the setting of a augmented prolonged labor, which is at higher risk of poor uterine contraction and PPH.
Read the detailed description
The increased incidence of uterine atony and PPH following exogenous oxytocin administration during labor augmentation is related to myometrial OTR desensitization to oxytocin. Calcium is an important messenger required within the uterine muscle cell to result in muscle contraction following administration of oxytocin. A physiological level of calcium is known to provide optimal contractility to normal myometrium.
Characterization of the importance of low, normal or high calcium levels in a setting of prolonged exogenous oxytocin administration may provide guidance for the use of exogenous calcium as a uterotonic adjunct; or for the optimization of serum calcium levels during augmented labor. In the clinical setting of failed labor augmentation and OTR desensitization, the role of serum calcium levels is not currently known.
The investigators' previously validated in-vitro model provides a solid foundation for the study of myometrial contractility under controlled conditions, without any confounders that could be encountered in clinical settings.
The results of this study will provide insight into the effect of low, normal or high calcium levels on the oxytocin pretreated (desensitized) and non-pretreated myometrium. Based on oxytocin dose-response curves after pretreatment to oxytocin and then subsequent exposure to either low, normal or high levels of calcium, the investigators will be able to determine the role of calcium on desensitized myometrium.
- Conditions
- Postpartum Hemorrhage
- Being tested
- Oxytocin, Calcium
- Keywords
- Uterine contraction, Oxytocin desensitization
- 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
Experiments will be conducted with some myometrial strips pretreated with oxytocin, and others without any oxytocin pretreatment
CalciumDrug
Calcium will be applied to the myometrial strips in 3 concentrations; 1.25mM (low), 2.5mM (normal) and 5.0mM (high). Myometrial strips will be either oxytocin pretreated, or non-oxytocin pretreated.
| Study group | Role | What they receive |
|---|---|---|
| 1.25mM Calcium-NO oxytocin pretreatment | Active comparator | Not described Receives: Drug: Calcium |
| 2.5mM Calcium-NO oxytocin pretreatment | Active comparator | Not described Receives: Drug: Calcium |
| 5.0mM Calcium-NO oxytocin pretreatment | Active comparator | Not described Receives: Drug: Calcium |
| 1.25mM Calcium-WITH oxytocin pretreatment | Active comparator | Not described Receives: Drug: Oxytocin; Drug: Calcium |
| 2.5mM Calcium-WITH oxytocin pretreatment | Active comparator | Not described Receives: Drug: Oxytocin; Drug: Calcium |
| 5.0mM Calcium-WITH oxytocin pretreatment | Active comparator | Not described Receives: Drug: Oxytocin; Drug: Calcium |
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: 8 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: 8 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: 8 hours
Integrated area under response curve (AUC)
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2014 (estimated)
- Study startNov 2014
- Primary completionMar 2015
- Study completionMar 2015
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
- 41 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
- NCT02274454
- Sponsor's protocol ID
- 14-02
- Status last verified
- May 2015
- First submitted
- 9 Oct 2014
- Last updated
- 27 May 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Effect of Extracellular Calcium on Oxytocin-induced Human Myometrial Contractility In-vitro
- ClinicalTrials.gov ID
- NCT02274454
- Acronym / sponsor ID
- 14-02
- Conditions
- Postpartum Hemorrhage
- Keywords
- Uterine contraction, Oxytocin desensitization
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- Nov 2014
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 24 Oct 2014 (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 a leading cause of maternal morbidity and mortality worldwide and is caused most commonly by poor uterine muscle tone after delivery. The first line agent used in the prevention and treatment of PPH is oxytocin, which acts by binding with the oxytocin receptor (OTR) found on myometrial cells to cause uterine contraction. It does this by increasing levels of calcium within the myometrial cell, which promotes contraction. Women who require augmentation of labor with intravenous oxytocin because of inadequate labor progression have been shown to be at increased risk of PPH. In-vitro human myometrial models have shown that following prolonged exposure to oxytocin there is desensitization of the myometrium resulting in a significant reduction in contractility upon delivery of further oxytocin.
Optimal levels of calcium are very important for contraction of the uterine muscle. Too little calcium results in a reduced contraction. Too much calcium may result in either stronger contractions, or even possibly relaxation of the muscle and therefore a reduced contraction. The investigators currently do not know the effects of calcium on the desensitized uterine muscle.
The investigators hypothesize that myometrial contractility following desensitization of the myometrium would be reduced in myometrial samples exposed to low calcium, when compared to normal calcium or high calcium exposure. These results will help in establishing whether myometrial contraction can be augmented by increasing calcium levels within the body, or by optimizing normal physiological calcium levels, in the setting of a augmented prolonged labor, which is at higher risk of poor uterine contraction and PPH.
Detailed description
The increased incidence of uterine atony and PPH following exogenous oxytocin administration during labor augmentation is related to myometrial OTR desensitization to oxytocin. Calcium is an important messenger required within the uterine muscle cell to result in muscle contraction following administration of oxytocin. A physiological level of calcium is known to provide optimal contractility to normal myometrium.
Characterization of the importance of low, normal or high calcium levels in a setting of prolonged exogenous oxytocin administration may provide guidance for the use of exogenous calcium as a uterotonic adjunct; or for the optimization of serum calcium levels during augmented labor. In the clinical setting of failed labor augmentation and OTR desensitization, the role of serum calcium levels is not currently known.
The investigators' previously validated in-vitro model provides a solid foundation for the study of myometrial contractility under controlled conditions, without any confounders that could be encountered in clinical settings.
The results of this study will provide insight into the effect of low, normal or high calcium levels on the oxytocin pretreated (desensitized) and non-pretreated myometrium. Based on oxytocin dose-response curves after pretreatment to oxytocin and then subsequent exposure to either low, normal or high levels of calcium, the investigators will be able to determine the role of calcium on desensitized myometrium.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 1.25mM Calcium-NO oxytocin pretreatment | Active comparator | Drug: Calcium |
| 2.5mM Calcium-NO oxytocin pretreatment | Active comparator | Drug: Calcium |
| 5.0mM Calcium-NO oxytocin pretreatment | Active comparator | Drug: Calcium |
| 1.25mM Calcium-WITH oxytocin pretreatment | Active comparator | Drug: Oxytocin, Drug: Calcium |
| 2.5mM Calcium-WITH oxytocin pretreatment | Active comparator | Drug: Oxytocin, Drug: Calcium |
| 5.0mM Calcium-WITH oxytocin pretreatment | Active comparator | Drug: Oxytocin, Drug: Calcium |
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 CD or first repeat CD
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 CD
- 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 CD 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: pitocinExperiments will be conducted with some myometrial strips pretreated with oxytocin, and others without any oxytocin pretreatment | Drug | 1.25mM Calcium-WITH oxytocin pretreatment, 2.5mM Calcium-WITH oxytocin pretreatment, 5.0mM Calcium-WITH oxytocin pretreatment |
| CalciumCalcium will be applied to the myometrial strips in 3 concentrations; 1.25mM (low), 2.5mM (normal) and 5.0mM (high). Myometrial strips will be either oxytocin pretreated, or non-oxytocin pretreated. | Drug | 1.25mM Calcium-NO oxytocin pretreatment, 1.25mM Calcium-WITH oxytocin pretreatment, 2.5mM Calcium-NO oxytocin pretreatment, 2.5mM Calcium-WITH oxytocin pretreatment, 5.0mM Calcium-NO oxytocin pretreatment, 5.0mM Calcium-WITH oxytocin pretreatment |
Primary outcome
Motility Index
Time frame: 8 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: 8 hours
Frequency of contraction
Time frame: 8 hours
Integrated area under response curve (AUC)
Time frame: 8 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 27 May 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mrinalini Balki, MD principal investigator
MOUNT SINAI HOSPITAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oxytocin and Calcium 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 27 May 2015. 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: 8 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 27 May 2015.