Double Uterotonic Agents for Postpartum Hemorrhage

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Stony Brook University

Disqualifiers: Under 18, Coagulation disorders, Placental accreta, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate postpartum period

1358 Participants Needed

Trial Summary

What is the purpose of this trial?

To determine the effectiveness of using two medications simultaneously versus one medication, as is standard of care, in preventing early postpartum hemorrhage. There have been studies that looked at giving two medications and that there were reduced odds of postpartum hemorrhage. Specific Aim 1: Determine if double simultaneous uterotonic agent regimen (misoprostol and oxytocin) is superior to single agent (oxytocin only) in reducing postpartum hemorrhage. Specific Aim 2: Determine any potential side effects of a double simultaneous uterotonic agentregimen (misoprostol and oxytocin) versus a single agent (oxytocin only).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that oxytocin is the gold standard for preventing and treating postpartum hemorrhage due to its proven effectiveness and safety. Misoprostol is also effective, especially in low-resource settings, because it induces uterine contractions, is stable at room temperature, and is easy to administer. ^{1 2 3 4 5}

Is the use of double uterotonic agents like misoprostol and oxytocin generally safe for humans?

Misoprostol and oxytocin are generally considered safe for preventing and treating postpartum hemorrhage, but misoprostol may cause more side effects like shivering and vomiting compared to oxytocin. Both drugs are widely used and recommended for their effectiveness, though misoprostol is often preferred in low-resource settings due to its stability and ease of use. ^{1 2 4 6 7}

How is the drug combination of Misoprostol and Oxytocin unique for treating postpartum hemorrhage?

The combination of Misoprostol and Oxytocin is unique because it uses two uterotonic agents that work together to enhance uterine contractions, which can be more effective than using Oxytocin alone. Misoprostol is particularly beneficial in low-resource settings due to its stability at room temperature and ease of administration, unlike Oxytocin, which requires refrigeration and skilled administration. ^{1 4 8 9 10}

Eligibility Criteria

This trial is for women aged 18 or older giving birth at Stony Brook University hospital who consent to participate. It excludes those planning a cesarean hysterectomy, with placental accreta spectrum disorders, allergies to prostaglandins, coagulation disorders, or under 18.

Inclusion Criteria

I am a woman over 18, giving birth at Stony Brook University hospital and agree to join the study.

Exclusion Criteria

I am a woman under 18 years old.

I have a known blood clotting disorder.

Women with planned cesarean hysterectomy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the standard postpartum Oxytocin IV or a combination of Misoprostol and Oxytocin to prevent postpartum hemorrhage

Immediate postpartum period

Follow-up

Participants are monitored for changes in postpartum hemorrhage blood loss volume and any serious adverse outcomes

1 year

Treatment Details

Interventions

• Misoprostol
• Oxytocin

Trial Overview The study tests if using two drugs (IV Oxytocin and Sublingual Misoprostol) together is better than just one (Oxytocin alone) in preventing early postpartum hemorrhage. The effectiveness and side effects of the double versus single medication regimen are being compared.

Participant Groups

Group I: Misoprostol plus intravenous Oxytocin Experimental Treatment 2 Interventions

Patients will receive standard postpartum Oxytocin IV per protocol and also be given Misoprostol 400 mcg sublingual

Group II: Intravenous Oxytocin only Active Control 1 Intervention

Patients will receive standard postpartum Oxytocin IV per protocol

Misoprostol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cytotec for:

• Abortion
• Cervical Ripening
• Gynecological Conditions
• Duodenal Ulcer
• NSAID-Induced Ulcer Prophylaxis
• Stomach Ulcer
• Labor Induction
• Postpartum Bleeding

Approved in European Union as Misoprostol for:

• Abortion
• Cervical Ripening
• Gynecological Conditions
• Duodenal Ulcer
• NSAID-Induced Ulcer Prophylaxis
• Stomach Ulcer
• Labor Induction
• Postpartum Bleeding

Approved in Canada as Misoprostol for:

• Abortion
• Cervical Ripening
• Gynecological Conditions
• Duodenal Ulcer
• NSAID-Induced Ulcer Prophylaxis
• Stomach Ulcer
• Labor Induction
• Postpartum Bleeding

Who Is Running the Clinical Trial?

Stony Brook University

Lead Sponsor

Trials

225

Recruited

41,700+

Findings from Research

In a study involving 64 women with primary postpartum hemorrhage, 800 mcg of misoprostol administered rectally was found to be more effective than the combination of Syntometrine and Syntocinon in stopping hemorrhage within 20 minutes.

The results showed a significant 28.1% improvement in hemorrhage control with misoprostol (p=0.01), highlighting its potential as a safe and effective treatment option for postpartum hemorrhage, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized study comparing rectally administered misoprostol versus Syntometrine combined with an oxytocin infusion for the cessation of primary post partum hemorrhage. Lokugamage, AU., Sullivan, KR., Niculescu, I., et al.[2019]

In a study involving five patients with severe delivery-induced hemorrhage due to uterine atony unresponsive to syntocinon, rectal administration of one misoprostol tablet effectively stopped the bleeding in less than 5 minutes for all patients.

No immediate side effects were observed, suggesting that misoprostol may be a safe and rapid intervention for managing severe hemorrhage in this context, warranting further research with larger sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rectal administration of misoprostol for delivery induced hemorrhage. Preliminary study]. Shojai, R., Piéchon, L., d'Ercole, C., et al.[2013]

In a study of 34 women undergoing elective cesarean sections, carbetocin was administered either as a bolus or an infusion, and both methods showed no significant differences in hemodynamic effects, indicating that the administration method does not impact its safety profile.

Carbetocin, a newer uterotonic agent, offers a longer duration of action compared to oxytocin, making it a potentially more effective option for preventing postpartum hemorrhage without the need for additional doses after delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of carbetocin administered as an intravenous bolus or infusion during cesarean delivery. Kwon, K., Kim, D., Jo, H., et al.[2022]

In low-income countries, up to 50% of hospital deliveries involve the use of oxytocin and misoprostol for labor induction and augmentation, highlighting their widespread application.

However, there are potential risks associated with these medications, including stillbirth, neonatal resuscitation needs, and uterine rupture, indicating a critical need for improved guidelines and community awareness regarding their safe use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to avoid iatrogenic morbidity and mortality while increasing availability of oxytocin and misoprostol for PPH prevention? Lovold, A., Stanton, C., Armbruster, D.[2016]

Oxytocin is the first-line treatment for preventing postpartum hemorrhage, and combining it with second-line uterotonics like methylergonovine or misoprostol can significantly enhance its effectiveness in reducing the risk of hemorrhage.

Tranexamic acid is effective and safe for decreasing maternal mortality associated with postpartum hemorrhage, and its prophylactic use may reduce the need for blood transfusions and additional uterotonics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing postpartum hemorrhage with combined therapy rather than oxytocin alone. Jones, AJ., Federspiel, JJ., Eke, AC.[2023]

A review of seven studies on oxytocin dosing for preventing postpartum hemorrhage found that higher doses (up to 80 IU/500 mL) and rapid bolus administration are more effective than lower doses or prolonged fixed doses.

The effectiveness of oxytocin in reducing blood loss and the need for additional treatments was particularly notable in cesarean deliveries, highlighting the importance of optimizing dosing strategies for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose and duration of oxytocin to prevent postpartum hemorrhage: a review. Roach, MK., Abramovici, A., Tita, AT.[2022]

References

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

A randomized study comparing rectally administered misoprostol versus Syntometrine combined with an oxytocin infusion for the cessation of primary post partum hemorrhage. [2019]

2. France pubmed.ncbi.nlm.nih.gov

[Rectal administration of misoprostol for delivery induced hemorrhage. Preliminary study]. [2013]

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

Carbetocin versus rectal misoprostol for management of third stage of labor among women with low risk of postpartum hemorrhage. [2020]

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

Misoprostol for the prevention and treatment of postpartum hemorrhage. [2013]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of carbetocin administered as an intravenous bolus or infusion during cesarean delivery. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Comparison of Clinical Efficacy and Safety between Misoprostol and Oxytocin in the Prevention of Postpartum Hemorrhage: A Meta-Analysis. [2023]

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

How to avoid iatrogenic morbidity and mortality while increasing availability of oxytocin and misoprostol for PPH prevention? [2016]

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

Preventing postpartum hemorrhage with combined therapy rather than oxytocin alone. [2023]

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

Dose and duration of oxytocin to prevent postpartum hemorrhage: a review. [2022]

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

Patterns of second-line uterotonic use in a large sample of hospitalizations for childbirth in the United States: 2007-2011. [2021]