Uterotonics for Postpartum Hemorrhage

Recruiting in Palo Alto (17 mi)

Overseen by Mrinalini Balki, MD

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Must not be taking: Insulin, Nifedipine, Labetalol, Magnesium

Disqualifiers: General anesthesia, Labor, Emergency CD, others

Trial Summary

What is the purpose of this trial?

This study will investigate the effects of drugs called "uterotonics" that help with the contraction of the uterus after a baby is born. This uterine contraction is very important to stop the bleeding after delivery. An uncontracted uterine state is called "uterine atony", which can lead to an excessive amount of post-delivery bleeding. Carbetocin is an uterotonic drug that works well to prevent post-delivery bleeding. In some cases, carbetocin is not enough to contract the uterus, and ongoing bleeding continues. When that happens, there are other uterotonic medications that can be used. In this study, we aim to find which uterotonic drug, amongst those available (oxytocin, carbetocin, ergometrine or carboprost), is more effective to lower the risk of post-delivery bleeding once carbetocin has already been administered. This study will be done by using a very small sample of uterine tissue, taken from the incision site, following delivery by cesarean section. The sample is taken to the laboratory and will be exposed to carbetocin followed by other uterotonic drugs. The information obtained from this study will help modify the treatment for uterine atony and post-delivery bleeding to lower the risk further.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial excludes patients on medications that could affect uterine muscle contractions, like insulin, nifedipine, labetalol, or magnesium sulfate.

What data supports the effectiveness of the drug for postpartum hemorrhage?

Research shows that carbetocin, a drug similar to oxytocin, is effective in preventing postpartum hemorrhage (excessive bleeding after childbirth) and can be used without refrigeration, making it more accessible in low-income countries. Studies have found it to be as effective as oxytocin in reducing blood loss after vaginal delivery. ^{1 2 3 4 5}

Is carbetocin safe for humans?

Carbetocin, a medication used to prevent excessive bleeding after childbirth, has been studied for its safety in several trials. These studies generally show that carbetocin is well-tolerated in humans, with safety profiles similar to other medications used for the same purpose, like oxytocin. ^{1 2 3 4 6}

How does the drug carbetocin differ from other treatments for postpartum hemorrhage?

Carbetocin is unique because it is available in a room temperature stable formulation, unlike oxytocin, which requires refrigeration. This makes carbetocin particularly useful in low-income countries where maintaining a cold chain for drug storage is challenging. ^{1 2 3 4 7}

Eligibility Criteria

This trial is for individuals who have recently given birth and are experiencing postpartum hemorrhage, a condition where the uterus does not contract strongly enough to stop bleeding. The study focuses on those who do not respond adequately to initial treatment with carbetocin.

Inclusion Criteria

Patients who give written consent to participate in this study

I am pregnant and between 37 to 41 weeks along.

I have not been given oxytocin for labor induction.

Exclusion Criteria

Emergency CD

I have chosen not to participate in this trial.

Placenta accreta spectrum disorder

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Sample Collection

Uterine tissue samples are collected from the incision site following delivery by cesarean section

Immediate post-delivery

1 visit (in-person)

Laboratory Testing

Uterine tissue samples are exposed to carbetocin followed by other uterotonic drugs to assess dose-response profiles

4 hours

Follow-up

Participants are monitored for any adverse effects post-sample collection and testing

1-2 weeks

Treatment Details

Interventions

• Comparing the Dose-response Profiles of Uterotonics After Initial Carbetocin Administration - an Ex-vivo Study in Desensitized Human Myometrium (Other)

Trial Overview The study tests the effectiveness of additional uterotonic drugs (ergonovine, carboprost, oxytocin) after carbetocin has been used. It aims to determine which drug best reduces the risk of continued bleeding in an ex-vivo setting using uterine tissue samples.

Participant Groups

Group I: Carbetocin Active Control 2 Interventions

Dose-response testing with increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-5 M to 10-5 M

Group II: Oxytocin Active Control 2 Interventions

Dose-response testing with increasing concentrations of oxytocin from 10-10 M to 10-5 M.

Group III: Ergometrine Active Control 3 Interventions

Dose-response testing with increasing concentrations of ergometrine from 10-10 M to 10-5 M

Group IV: Carboprost Active Control 3 Interventions

Dose-response testing with increasing concentrations of carboprost from 10-10 M to 10-5 M

Group V: Control Placebo Group 2 Interventions

No drug added to physiological salt solution (PSS).

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mount Sinai Hospital Toronto, Canada

Who Is Running the Clinical Trial?

Samuel Lunenfeld Research Institute, Mount Sinai Hospital Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Room temperature stable carbetocin for the prevention of postpartum haemorrhage during the third stage of labour in women delivering vaginally: study protocol for a randomized controlled trial. [2022] Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in low-income countries and contributes to nearly a quarter of maternal deaths globally. The current available interventions for prevention of postpartum haemorrhage, oxytocin and carbetocin, are limited by their need for refrigeration to maintain potency, as the ability to maintain a cold chain across the drug distribution and storage network is inconsistent, thus restricting their use in countries with the highest burden of maternal mortality. We describe a randomized, double-blind non-inferiority trial comparing a newly developed room temperature stable formulation of carbetocin to the standard intervention (oxytocin) for the prevention of PPH after vaginal birth.

2. United States pubmed.ncbi.nlm.nih.gov

Effects of carbetocin combined with ergometrine maleate on blood loss and coagulation function of puerperae with postpartum haemorrhage. [2023] To determine the effects of carbetocin combined with ergometrine maleate on blood loss and coagulation function of puerperae with postpartum haemorrhage (PH).

3. United States pubmed.ncbi.nlm.nih.gov

Carbetocin vs oxytocin for prevention of postpartum hemorrhage after vaginal delivery: A meta-analysis. [2022] To evaluate the efficacy and safety of carbetocin for prevention of postpartum hemorrhage in women undergoing vaginal delivery compared with oxytocin.

4. England pubmed.ncbi.nlm.nih.gov

Carbetocin for the prevention of postpartum hemorrhage: a systematic review and meta-analysis of randomized controlled trials. [2022] To compare the efficacy and safety profile of carbetocin with other uterotonic agents in preventing postpartum hemorrhage.

5. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of carbetocin and oxytocin for the prevention of postpartum hemorrhage following vaginal delivery:a double-blind randomized trial. [2019] To compare the efficacy of a single 100 micro g intramuscular (IM) carbetocin injection, a long-acting oxytocin agonist, to a 2-hour 10 IU oxytocin intravenous (IV) infusion, in reducing the incidence and severity of postpartum hemorrhage (PPH) in women at risk for this condition.

6. Ireland pubmed.ncbi.nlm.nih.gov

Ascending dose tolerance study of intramuscular carbetocin administered after normal vaginal birth. [2019] To determine the maximum tolerated dose (MTD) of carbetocin (a long-acting synthetic analogue of oxytocin), when administered immediately after vaginal delivery at term.

7. Netherlands pubmed.ncbi.nlm.nih.gov

What does basic science tell us about the use of uterotonics? [2020] Pharmacotherapy with uterotonics remains the mainstay of the management for post-partum haemorrhage. Clinical studies evaluating the efficacy of these drugs are fraught with confounders, which may influence uterine contractility and blood loss. For this reason, a range of techniques have been developed to study myometrial function in vitro, allowing for the comparison of various drugs in a controlled-simulated physiological environment. In this review, we focus on the main classes of uterotonic drugs and outline their molecular and physiological basis of action. We explore the evidence related to appropriate drug dosing and relative efficacy, and compare the evidence gleaned from clinical and in vitro studies. We discuss the mechanism of oxytocin desensitisation and how basic science has helped us understand this phenomenon. We also discuss the in vitro research findings for each of the main classes of uterotonic drugs that have contributed to an improved understanding of the management of post-partum haemorrhage and, ultimately, better care for mothers.