Postpartum HemorrhageNCT03408054
The Relaxant Effect of Nitroglycerin on Oxytocin Desensitized Human Myometrium
A study testing Oxytocin and Nitroglycerin in people with Postpartum Hemorrhage, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site in Canada.
Trial summary
Oxytocin causes myometrial contraction via the oxytocin receptor (OTR). Desensitization of the OTR after exposure to oxytocin has been demonstrated in previous studies. The resultant need for a higher oxytocin dose to cause adequate uterine contraction in vivo has also been demonstrated in laboring women having… 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 Nitroglycerin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteCanada
- Study dates
- 3 Jan 2018to 13 Apr 2018
- 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
Official title: The Relaxant Effect of Nitroglycerin on Oxytocin Desensitized Human Myometrium and the Return of Contractility on Re-exposure to Oxytocin- an in Vitro Study
Oxytocin causes myometrial contraction via the oxytocin receptor (OTR). Desensitization of the OTR after exposure to oxytocin has been demonstrated in previous studies. The resultant need for a higher oxytocin dose to cause adequate uterine contraction in vivo has also been demonstrated in laboring women having received oxytocin for labor augmentation.
Achieving rapid uterine relaxation can be invaluable for maternal and fetal wellbeing in some acute obstetric emergency settings. Nitroglycerin has become a commonly used agent for achieving rapid uterine relaxation amongst obstetric anesthesiologists.
Read more
Previous studies have concluded that oxytocin can be used to re-establish uterine tone following nitroglycerin mediated relaxation. However, no studies to date have looked at the effects of nitroglycerin mediated relaxation of uterine muscle that has undergone oxytocin receptor desensitization. Nor has the response to oxytocin re-exposure and return of contractility in desensitized myometrium (following nitroglycerin) been examined.
The investigators hypothesize that nitroglycerin will reduce and inhibit uterine contractions in both oxytocin pre-treated myometrium, as well as untreated myometrium in a dose dependent fashion, but that myometrium that has undergone OTR desensitization will require less nitroglycerin for contractions to abate.
The investigators also expect that the dose of oxytocin required to re-establish equivalent contractions will be higher in the myometrial samples which have undergone nitroglycerin mediated relaxation.
Read the detailed description
Oxytocin and nitroglycerin have opposing actions on the myometrium. The pharmacological properties of quick onset and offset of action of nitroglycerin have made this the preferred drug to be used in acute scenarios where uterine relaxation is necessary.
As nitroglycerin causes changes to intracellular calcium levels and the ability uterine muscle to engage in effective contraction, it is plausible that the effects of nitroglycerin may interfere with subsequent uterine contractility and action of oxytocin.
The situation where a difficult fetal extraction is encountered at cesarean section may be in two broad groups of patients. Those pre-exposed to oxytocin and those with an oxytocin naïve myometrium. Given the large observational variation in dosages of nitroglycerin usage seen in the literature we feel it is vital to investigate whether pre-exposure to oxytocin impacts on the ability of nitroglycerin to relax uterine smooth muscle. Furthermore, once the uterus has relaxed following nitroglycerin exposure, is there a need for higher doses of oxytocin to be administered in order to re-engage the uterus in effective contraction? And is this requirement further exacerbated by the phenomenon of oxytocin receptor desensitization? These clinically important questions will be addressed by the design of this in vitro myometrial study.
- Conditions
- Postpartum Hemorrhage
- Being tested
- Oxytocin, Nitroglycerin
- Keywords
- Uterine contraction, Oxytocin, Nitroglycerin
- 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 Duratocin, pitocin
Oxytocin 10-5M solution
NitroglycerinDrug
Nitroglycerin 25-1000mcg
| Study group | Role | What they receive |
|---|---|---|
| Control group | No intervention | No oxytocin desensitization (pretreatment), no nitroglycerin |
| Oxytocin desensitized - no nitroglycerin | Active comparator | Pretreated with oxytocin, no nitroglycerin exposure Receives: Drug: Oxytocin |
| Oxytocin desensitized - plus nitroglycerin | Active comparator | Pretreated with oxytocin followed by nitroglycerin exposure Receives: Drug: Oxytocin; Drug: Nitroglycerin |
| Non oxytocin desensitized - plus nitroglycerin | Active comparator | No oxytocin pretreatment, followed by nitroglycerin exposure Receives: Drug: Nitroglycerin |
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 posted23 Jan 2018
- Study start3 Jan 2018
- Primary completion13 Apr 2018
- Study completion13 Apr 2018
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
- 17 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
- NCT03408054
- Sponsor's protocol ID
- 18-01
- Status last verified
- Feb 2019
- First submitted
- 17 Jan 2018
- Last updated
- 22 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Jayasooriya GS, Carvalho JCA, Luca A, Balki M. The Effects of Nitroglycerin on the Oxytocin Dose-Response Profile in Oxytocin-Desensitized and Naive Human Myometrium: An In Vitro Study. Anesth Analg. 2021 Jan;132(1):231-239. doi: 10.1213/ANE.0000000000005055.
PubMed 32858531
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Relaxant Effect of Nitroglycerin on Oxytocin Desensitized Human Myometrium and the Return of Contractility on Re-exposure to Oxytocin- an in Vitro Study
- ClinicalTrials.gov ID
- NCT03408054
- Acronym / sponsor ID
- 18-01
- Conditions
- Postpartum Hemorrhage
- Keywords
- Uterine contraction, Oxytocin, Nitroglycerin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- 3 Jan 2018 (actual)
- Primary completion
- 13 Apr 2018 (actual)
- Study completion
- 13 Apr 2018 (actual)
- First posted
- 23 Jan 2018 (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.
Oxytocin causes myometrial contraction via the oxytocin receptor (OTR). Desensitization of the OTR after exposure to oxytocin has been demonstrated in previous studies. The resultant need for a higher oxytocin dose to cause adequate uterine contraction in vivo has also been demonstrated in laboring women having received oxytocin for labor augmentation.
Achieving rapid uterine relaxation can be invaluable for maternal and fetal wellbeing in some acute obstetric emergency settings. Nitroglycerin has become a commonly used agent for achieving rapid uterine relaxation amongst obstetric anesthesiologists.
Previous studies have concluded that oxytocin can be used to re-establish uterine tone following nitroglycerin mediated relaxation. However, no studies to date have looked at the effects of nitroglycerin mediated relaxation of uterine muscle that has undergone oxytocin receptor desensitization. Nor has the response to oxytocin re-exposure and return of contractility in desensitized myometrium (following nitroglycerin) been examined.
The investigators hypothesize that nitroglycerin will reduce and inhibit uterine contractions in both oxytocin pre-treated myometrium, as well as untreated myometrium in a dose dependent fashion, but that myometrium that has undergone OTR desensitization will require less nitroglycerin for contractions to abate.
The investigators also expect that the dose of oxytocin required to re-establish equivalent contractions will be higher in the myometrial samples which have undergone nitroglycerin mediated relaxation.
Detailed description
Oxytocin and nitroglycerin have opposing actions on the myometrium. The pharmacological properties of quick onset and offset of action of nitroglycerin have made this the preferred drug to be used in acute scenarios where uterine relaxation is necessary.
As nitroglycerin causes changes to intracellular calcium levels and the ability uterine muscle to engage in effective contraction, it is plausible that the effects of nitroglycerin may interfere with subsequent uterine contractility and action of oxytocin.
The situation where a difficult fetal extraction is encountered at cesarean section may be in two broad groups of patients. Those pre-exposed to oxytocin and those with an oxytocin naïve myometrium. Given the large observational variation in dosages of nitroglycerin usage seen in the literature we feel it is vital to investigate whether pre-exposure to oxytocin impacts on the ability of nitroglycerin to relax uterine smooth muscle. Furthermore, once the uterus has relaxed following nitroglycerin exposure, is there a need for higher doses of oxytocin to be administered in order to re-engage the uterus in effective contraction? And is this requirement further exacerbated by the phenomenon of oxytocin receptor desensitization? These clinically important questions will be addressed by the design of this in vitro myometrial study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | –No oxytocin desensitization (pretreatment), no nitroglycerin |
| Oxytocin desensitized - no nitroglycerin | Active comparator | Drug: OxytocinPretreated with oxytocin, no nitroglycerin exposure |
| Oxytocin desensitized - plus nitroglycerin | Active comparator | Drug: Oxytocin, Drug: NitroglycerinPretreated with oxytocin followed by nitroglycerin exposure |
| Non oxytocin desensitized - plus nitroglycerin | Active comparator | Drug: NitroglycerinNo oxytocin pretreatment, followed by nitroglycerin exposure |
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: Duratocin, pitocinOxytocin 10-5M solution | Drug | Oxytocin desensitized - no nitroglycerin, Oxytocin desensitized - plus nitroglycerin |
| NitroglycerinNitroglycerin 25-1000mcg | Drug | Non oxytocin desensitized - plus nitroglycerin, Oxytocin desensitized - plus nitroglycerin |
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 22 Feb 2019.
- Derived from this study: PubMed 32858531Jayasooriya GS, Carvalho JCA, Luca A, Balki M. The Effects of Nitroglycerin on the Oxytocin Dose-Response Profile in Oxytocin-Desensitized and Naive Human Myometrium: An In Vitro Study. Anesth Analg. 2021 Jan;132(1):231-239. doi: 10.1213/ANE.0000000000005055.
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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 Nitroglycerin 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 22 Feb 2019. 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 NCT03408054, 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 22 Feb 2019.