Postpartum HemorrhageNCT02338089
Investigating the Effect of Pulsatile Administration of Oxytocin on the Desensitization of Human Myometrium In-vitro
A study testing Oxytocin 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 (myometrium) tone after delivery. The first line agent used in the prevention and treatment of PPH is oxytocin. 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
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2015to Jun 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 Cesarean delivery or first repeat Cesarean delivery
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 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 (myometrium) tone after delivery. The first line agent used in the prevention and treatment of PPH is oxytocin.
Women who require augmentation of labor with intravenous oxytocin because of inadequate labor progression have been shown to be at increased risk of PPH. Typically, for augmentation of labor, oxytocin is used as a continuous infusion, with no consensus on the initial dose, its increments or maximal limit. High concentration continuous oxytocin infusions are not without theirs risks, which include hyperstimulation, fetal distress, as well as uterine rupture.
Read more
Studies have shown the clinical benefits of pulsatile oxytocin delivery for labor induction and augmentation with regards to requirement of less total oxytocin, similar uterine contractility and similar rates of caesarean delivery when used for labor induction and augmentation. However, the rate of PPH as a primary outcome measure has not been investigated. Therefore we currently do not know the effect of pulsatile oxytocin delivery on the rate of PPH.
The investigators hypothesize that the effect of myometrial desensitization following pulsatile oxytocin exposure would be lower when compared to continuous oxytocin exposure. These results will help in establishing whether myometrial contractility and sensitivity to oxytocin can be better preserved by delivery of pulsatile oxytocin, rather than continuous oxytocin for labor induction and augmentation, and thereby result in less PPH.
Read the detailed description
Typically labor can be augmented by exposure to high levels of continuous oxytocin, for prolonged periods. The increased incidence of uterine atony and PPH following exogenous oxytocin administration during labor augmentation is related to myometrial oxytocin receptor desensitization to oxytocin.
Human clinical trials have shown the benefits of pulsatile oxytocin administration for labor induction and augmentation, which include requirement of less total oxytocin, similar uterine contractility and similar rates of cesarean delivery. However, the outcome of the effect on PPH is not currently known.
Characterization of the effect of pulsatile oxytocin on the desensitization of myometrium when compared to the effect of continuous oxytocin, may provide guidance for the delivery of pulsatile oxytocin for labor induction and augmentation to protect against the otherwise higher risk of PPH. Furthermore, the delivery of pulsatile oxytocin may be considered in subgroups who are already at higher risk of PPH, and require labor augmentation.
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 level of desensitization of human myometrium following exposure to pulsatile oxytocin. Based on oxytocin dose-response curves after pretreatment to continuous oxytocin and pretreatment to pulsatile oxytocin, we will be able to determine the extent of desensitized myometrium following each delivery method.
- Conditions
- Postpartum Hemorrhage
- Being tested
- Oxytocin
- 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
Oxytocin, 100 micromolar solution
| Study group | Role | What they receive |
|---|---|---|
| Control (no oxytocin) pretreatment | No intervention | Physiological saline solution (PSS). Every 15-minutes, the PSS will be flushed and fresh PSS will be added. |
| Continuous oxytocin (desensitizing) pretreatment | Active comparator | Continuous oxytocin 10-5M. This desensitizing treatment is based on previous experiments in our laboratory demonstrating this phenomenon (reference 25 of Internal Review). The desensitizing pretreatment mimics the clinical setting of labor augmentation. Every 15-minutes, the 10-5M oxytocin will be flushed and fresh 10-5M oxytocin will be added. Receives: Drug: Oxytocin |
| Pulsatile oxytocin pretreatment | Active comparator | 15-minutes of 10-5M oxytocin, followed by PSS for 15-minutes, followed by 10-5M oxytocin, followed by 15-minutes PSS, and so-on, for a total duration of two-hours, Receives: Drug: Oxytocin |
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 posted14 Jan 2015 (estimated)
- Study startJan 2015
- Primary completionJun 2015
- Study completionJun 2015
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
- 18 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
- NCT02338089
- Sponsor's protocol ID
- 14-06
- Status last verified
- Sep 2015
- First submitted
- 9 Jan 2015
- Last updated
- 4 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Talati C, Carvalho JCA, Luca A, Balki M. The Effect of Intermittent Oxytocin Pretreatment on Oxytocin-Induced Contractility of Human Myometrium In Vitro. Anesth Analg. 2019 Apr;128(4):671-678. doi: 10.1213/ANE.0000000000002834.
PubMed 29401080
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Effect of Pulsatile Administration of Oxytocin on the Desensitization of Human Myometrium In-vitro
- ClinicalTrials.gov ID
- NCT02338089
- Acronym / sponsor ID
- 14-06
- Conditions
- Postpartum Hemorrhage
- Keywords
- Uterine contraction, Oxytocin desensitization
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 14 Jan 2015 (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 (myometrium) tone after delivery. The first line agent used in the prevention and treatment of PPH is oxytocin.
Women who require augmentation of labor with intravenous oxytocin because of inadequate labor progression have been shown to be at increased risk of PPH. Typically, for augmentation of labor, oxytocin is used as a continuous infusion, with no consensus on the initial dose, its increments or maximal limit. High concentration continuous oxytocin infusions are not without theirs risks, which include hyperstimulation, fetal distress, as well as uterine rupture.
Studies have shown the clinical benefits of pulsatile oxytocin delivery for labor induction and augmentation with regards to requirement of less total oxytocin, similar uterine contractility and similar rates of caesarean delivery when used for labor induction and augmentation. However, the rate of PPH as a primary outcome measure has not been investigated. Therefore we currently do not know the effect of pulsatile oxytocin delivery on the rate of PPH.
The investigators hypothesize that the effect of myometrial desensitization following pulsatile oxytocin exposure would be lower when compared to continuous oxytocin exposure. These results will help in establishing whether myometrial contractility and sensitivity to oxytocin can be better preserved by delivery of pulsatile oxytocin, rather than continuous oxytocin for labor induction and augmentation, and thereby result in less PPH.
Detailed description
Typically labor can be augmented by exposure to high levels of continuous oxytocin, for prolonged periods. The increased incidence of uterine atony and PPH following exogenous oxytocin administration during labor augmentation is related to myometrial oxytocin receptor desensitization to oxytocin.
Human clinical trials have shown the benefits of pulsatile oxytocin administration for labor induction and augmentation, which include requirement of less total oxytocin, similar uterine contractility and similar rates of cesarean delivery. However, the outcome of the effect on PPH is not currently known.
Characterization of the effect of pulsatile oxytocin on the desensitization of myometrium when compared to the effect of continuous oxytocin, may provide guidance for the delivery of pulsatile oxytocin for labor induction and augmentation to protect against the otherwise higher risk of PPH. Furthermore, the delivery of pulsatile oxytocin may be considered in subgroups who are already at higher risk of PPH, and require labor augmentation.
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 level of desensitization of human myometrium following exposure to pulsatile oxytocin. Based on oxytocin dose-response curves after pretreatment to continuous oxytocin and pretreatment to pulsatile oxytocin, we will be able to determine the extent of desensitized myometrium following each delivery method.
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 | –Physiological saline solution (PSS). Every 15-minutes, the PSS will be flushed and fresh PSS will be added. |
| Continuous oxytocin (desensitizing) pretreatment | Active comparator | Drug: OxytocinContinuous oxytocin 10-5M. This desensitizing treatment is based on previous experiments in our laboratory demonstrating this phenomenon (reference 25 of Internal Review). The desensitizing pretreatment mimics the clinical setting of labor augmentation. Every 15-minutes, the 10-5M oxytocin will be flushed and fresh 10-5M oxytocin will be added. |
| Pulsatile oxytocin pretreatment | Active comparator | Drug: Oxytocin15-minutes of 10-5M oxytocin, followed by PSS for 15-minutes, followed by 10-5M oxytocin, followed by 15-minutes PSS, and so-on, for a total duration of two-hours, |
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
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, 100 micromolar solution | Drug | Continuous oxytocin (desensitizing) pretreatment, Pulsatile 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 4 Sep 2015.
- Derived from this study: PubMed 29401080Talati C, Carvalho JCA, Luca A, Balki M. The Effect of Intermittent Oxytocin Pretreatment on Oxytocin-Induced Contractility of Human Myometrium In Vitro. Anesth Analg. 2019 Apr;128(4):671-678. doi: 10.1213/ANE.0000000000002834.
Related trials for Postpartum Hemorrhage
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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 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 4 Sep 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?
On the ClinicalTrials.gov record for NCT02338089, 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 4 Sep 2015.