Carbetocin for Postpartum Hemorrhage

Overseen By Mrinalini Balki, MD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Must not be taking: Nifedipine, Labetalol, Magnesium sulphate

Disqualifiers: General anesthesia, Multiple cesareans, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how different calcium levels affect the effectiveness of carbetocin, a drug used to prevent excessive bleeding after childbirth (postpartum hemorrhage). Researchers seek to determine if maintaining normal calcium levels can enhance carbetocin's effectiveness, particularly in women with or without prior exposure to oxytocin. The trial will test various calcium levels with carbetocin to identify the most effective combination. Pregnant women not yet in labor, scheduled for a planned cesarean delivery, and without previous use of certain medications may be suitable candidates for this trial. As an unphased trial, this study offers participants the chance to contribute to foundational research that could improve postpartum care.

Will I have to stop taking my current medications?

If you are taking medications like nifedipine, labetalol, or magnesium sulphate, you may need to stop them, as they can affect myometrial contractility (the ability of the uterus to contract).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that carbetocin is a well-tolerated option for preventing heavy bleeding after childbirth (postpartum hemorrhage or PPH) during a cesarean delivery. Research indicates it causes less vomiting than other treatments, making it a promising choice for women undergoing a cesarean section.

Carbetocin is similar to oxytocin, a drug commonly used to help the uterus contract. Although carbetocin is not yet approved for treating PPH directly, it is recommended for prevention. This indicates the drug is safe for use in certain childbirth situations, though not during pregnancy itself.

Overall, evidence supports carbetocin as a safe and effective option for preventing PPH, especially compared to other drugs that help the uterus contract. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Carbetocin is unique because it offers a novel approach to managing postpartum hemorrhage. Unlike the standard treatment, oxytocin, carbetocin has a longer-lasting effect, which means it could potentially reduce the need for repeated dosing. Additionally, carbetocin is heat-stable, making it easier to store and use in various settings, especially in regions with limited refrigeration facilities. Researchers are excited about its potential to improve maternal outcomes by providing a more efficient and practical solution to controlling excessive bleeding after childbirth.

What evidence suggests that this trial's treatments could be effective for postpartum hemorrhage?

Studies have shown that carbetocin effectively prevents heavy bleeding after childbirth, known as postpartum hemorrhage (PPH). It reduces blood loss and the risk of PPH more effectively than oxytocin, another common treatment. Specifically, carbetocin is associated with fewer high-risk hospital admissions and less severe bleeding. Some research also indicates that it can reduce costs by lowering the expenses and health impacts related to PPH. This trial will explore various treatment arms involving different concentrations of calcium chloride and carbetocin, with and without oxytocin pre-exposure, to further evaluate carbetocin's effectiveness and potential benefits in managing PPH. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for women at high risk of postpartum hemorrhage (PPH), a condition where there's excessive bleeding after childbirth. It aims to find better treatments for those with uterine atony, which is when the uterus doesn't contract well.

Inclusion Criteria

I am pregnant, not in labor, and between 37 to 41 weeks along.

I have not been given oxytocin and am scheduled for my first or second C-section with spinal or epidural anesthesia.

Exclusion Criteria

More than 1 previous cesarean delivery

I have had uterine atony in the past.

I need general anesthesia for my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Ex-Vivo Testing

Dose-response testing with varying concentrations of calcium chloride and carbetocin, with and without oxytocin pre-exposure

4 hours

Follow-up

Participants are monitored for safety and effectiveness after ex-vivo testing

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carbetocin

Trial Overview The study tests how different levels of calcium in the blood affect the ability of Carbetocin, a drug similar to Oxytocin, to make the uterus contract. The focus is on whether normal calcium levels improve these contractions more than low or high levels.

How Is the Trial Designed?

Group I: Calcium 1.25nM with NO oxytocin pre-exposure Active Control 2 Interventions

Dose-response testing with 1.25nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with NO oxytocin pre-exposure

Group II: Calcium 2.5nM with NO oxytocin pre-exposure Active Control 2 Interventions

Dose-response testing with 2.5nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with NO oxytocin pre-exposure

Group III: Calcium 5.0nM with NO oxytocin pre-exposure Active Control 2 Interventions

Dose-response testing with 5.0nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with NO oxytocin pre-exposure

Group IV: Calcium 1.25nM with oxytocin pre-exposure Active Control 3 Interventions

Dose-response testing with 1.25nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with oxytocin pre-exposure

Group V: Calcium 2.5nM with oxytocin pre-exposure Active Control 3 Interventions

Dose-response testing with 2.5nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with oxytocin pre-exposure

Group VI: Calcium 5.0nM with oxytocin pre-exposure Active Control 3 Interventions

Dose-response testing with 5.0nM calcium chloride, and increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M, with oxytocin pre-exposure

Who Is Running the Clinical Trial?

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Lead Sponsor

Trials

132

Recruited

11,400+

Published Research Related to This Trial

Carbetocin significantly reduced postpartum hemorrhage (PPH) compared to oxytocin, with lower bleeding amounts (337.73 mL vs. 378 mL) and a lower occurrence of PPH (4% vs. 16%) in a study of 200 women.

Carbetocin also resulted in better hemoglobin levels post-delivery and caused fewer hemodynamic changes, making it a safer alternative to oxytocin, despite a higher incidence of tachycardia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbetocin versus oxytocin for prevention of postpartum hemorrhage after vaginal delivery in high risk women. Maged, AM., Hassan, AM., Shehata, NA.[2023]

Carbetocin significantly reduces the need for additional uterotonic agents compared to oxytocin in women after cesarean delivery, indicating its efficacy in preventing postpartum hemorrhage.

Carbetocin has a lower risk of adverse effects compared to syntometrine during vaginal delivery, making it a potentially safer alternative for preventing postpartum hemorrhage, with similar effectiveness to other uterotonics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbetocin for the prevention of postpartum hemorrhage: a systematic review and meta-analysis of randomized controlled trials. Jin, B., Du, Y., Zhang, F., et al.[2022]

Carbetocin is likely as effective as oxytocin and syntometrine in preventing postpartum hemorrhage, based on a review of various studies that assessed multiple outcome measures.

The safety profile of carbetocin is similar to that of oxytocin, which is currently the standard treatment for this condition, although further research is necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbetocin for the prevention of postpartum hemorrhage: a systematic review. Peters, NC., Duvekot, JJ.[2018]

A meta-analysis of 5 randomized controlled trials involving 30,314 women found that carbetocin is as effective as oxytocin in preventing postpartum hemorrhage during vaginal delivery, with no significant difference in blood loss of 500 ml or more.

Both carbetocin and oxytocin showed similar safety profiles, with no notable differences in side effects or the need for additional interventions, suggesting that the choice between them may depend on cost-effectiveness rather than efficacy or safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbetocin vs oxytocin for prevention of postpartum hemorrhage after vaginal delivery: A meta-analysis. Jin, XH., Li, D., Li, X.[2022]

In a study of 160 hypertensive pregnant women undergoing cesarean section, carbetocin was found to significantly reduce postoperative blood loss compared to oxytocin, with blood loss averaging 424.75 ml in the carbetocin group versus 679.5 ml in the oxytocin group.

Carbetocin also maintained hemoglobin levels post-delivery, while oxytocin led to a significant decrease in hemoglobin, indicating that carbetocin may be a safer option for preventing postpartum hemorrhage in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbetocin versus oxytocin for prevention of postpartum hemorrhage in hypertensive women undergoing elective cesarean section. Ibrahim, ZM., Sayed Ahmed, WA., Abd El-Hamid, EM., et al.[2021]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK546425/

Carbetocin for the Prevention of Post-Partum Hemorrhage In the primary studies, carbetocin was associated with similar or more effectiveness regarding the prevention of PPH, reducing additional ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1028455916301917

Carbetocin in prevention of postpartum hemorrhage In Taiwan, prophylactic use of carbetocin resulted in significantly less blood loss and incidence of PPH in cesarean than in vaginal deliveries.

3. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0279130

Cost-effectiveness analysis of carbetocin for prevention of ... In base-case analysis, carbetocin (versus oxytocin) reduced PPH-related cost (by USD29 per birth), PPH ≥500 mL and ≥1,500 mL (by 13.7 and 1.9 per 1,000 births), ...

4. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.18358

Carbetocin for Postpartum Haemorrhage Prophylaxis in All ... Carbetocin is associated with reduced blood loss and the rate of PPH compared to Oxytocin. Associated reductions in admissions to high ...

5. bmchealthservres.biomedcentral.com bmchealthservres.biomedcentral.com/articles/10.1186/s12913-023-09263-4

Cost-effectiveness and budget impact of heat-stable ... Compared to oxytocin, heat-stable carbetocin avoided 5,468 additional PPH events, 5 deaths, and 244 DALYs per 100,000 births. Projected direct ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02304055

Carbetocin Versus Oxytocin in the Management of Atonic ... Oxytocin is currently the uterotonic of first choice. It has proven to decrease the incidence of PPH by 40 % and has a rapid onset of action and a good safety ...

7. ghsupplychain.org ghsupplychain.org/sites/default/files/2023-07/HSC_20230630.pdf

HEAT-STABLE CARBETOCIN Unlike oxytocin, misoprostol and ergometrine, carbetocin is not indicated for treatment of PPH, and it is contraindicated during pregnancy and must not be used ...

8. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/full/10.1002/prp2.745

Side‐effects of carbetocin to prevent postpartum hemorrhage ... The use of carbetocin had a lower risk of vomiting in intravenously (0.53, 0.30 to 0.93) and cesarean birth (0.51, 0.32 to 0.81) women, and had ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1805489

Heat-Stable Carbetocin versus Oxytocin to Prevent ... Heat-stable carbetocin was noninferior to oxytocin for the prevention of blood loss of at least 500 ml or the use of additional uterotonic agents.