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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether using two medications, misoprostol and oxytocin, is more effective than using only oxytocin to prevent heavy bleeding after childbirth. Researchers aim to determine if this combination reduces postpartum hemorrhage (severe bleeding after giving birth) and identify any side effects. Women giving birth at Stony Brook University Hospital, who do not have specific health conditions like blood clotting issues or certain allergies, might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to important medical advancements.

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.

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

Research has shown that using both misoprostol and oxytocin together can lower the risk of heavy bleeding after childbirth, known as postpartum hemorrhage. Studies have found that misoprostol significantly reduces bleeding when used to prevent this condition. However, oxytocin is often preferred due to its typically fewer side effects.

Regarding safety, previous studies suggest that oxytocin is generally well-tolerated. While misoprostol is effective, it may cause more side effects than oxytocin, such as shivering or fever.

Since this trial is in an advanced stage, earlier studies likely demonstrated that the treatment is safe enough for further testing. For some individuals, using both medications together might offer better protection against postpartum bleeding, but potential side effects should be considered. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for postpartum hemorrhage?

Researchers are excited about combining Misoprostol with Oxytocin for treating postpartum hemorrhage because it offers a potentially more effective approach than using Oxytocin alone. Oxytocin is the standard treatment, working by stimulating uterine contractions to reduce bleeding. However, Misoprostol, administered sublingually, adds a new dimension by enhancing these contractions and potentially speeding up the response time. This combination could lead to better management of postpartum hemorrhage, providing a quicker and more robust solution to a critical maternal health issue.

What evidence suggests that using misoprostol and oxytocin together could be effective for preventing postpartum hemorrhage?

Research has shown that using two medications together, misoprostol and oxytocin, might help reduce heavy bleeding after childbirth, known as postpartum hemorrhage (PPH). In this trial, one group of participants will receive only intravenous oxytocin, which is already known to lower the need for a blood transfusion and has fewer side effects than misoprostol alone. Another group will receive both misoprostol and intravenous oxytocin. Studies have found that misoprostol alone is not as effective as oxytocin for preventing severe blood loss. However, using both medications together could lead to better results. Researchers aim to determine if this combination works better for preventing PPH. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3964754/

Safety and Efficacy of Misoprostol versus Oxytocin for the ... They found no significant difference between using sublingual 800 mcg misoprostol and 40 IU intravenous oxytocin for PPH [15, 17]. Both studies were conducted ...

2. aafp.org aafp.org/pubs/afp/issues/2021/0601/p656.pdf

Medicine by the Numbers Oxytocin therapy decreases the chances of a blood transfusion compared with misopros- tol and has fewer adverse effects. Weak patient- oriented ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9941051/

Preventing postpartum hemorrhage with combined therapy ... In a 2020 Cochrane systematic review, misoprostol alone used as first-line treatment of PPH was found to be less effective than oxytocin for blood loss ≥1000 mL ...

4. ajog.org ajog.org/article/S0002-9378(25)00697-0/fulltext

Prophylactic oxytocin dose following vaginal birth to ... Lower doses (2.5–3 IU) likely reduced the risk of severe blood loss (moderate certainty) and may reduce additional uterotonic use (low certainty) ...

5. evidencebasedbirth.com evidencebasedbirth.com/evidence-on-pitocin-during-the-third-stage-of-labor/

Evidence on: Pitocin® During the Third Stage of Labor Pitocin® after birth with active management does not directly reduce blood loss caused by tissue damage (these tears must be repaired to stop the bleeding), but ...

6. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.18197

Misoprostol Versus Oxytocin for the Prevention of Postpartum ... Analysis of trustworthy data showed that PR misoprostol was associated with a non-significant decrease in PPH ≥ 1000 mL (5 RCTs, 1226 ...

7. clinicaltrials.gov clinicaltrials.gov/show/NCT01863706

Misoprostol Versus Oxytocin for Prevention of Post Partum ... Oxytocin is widely used for prevention of PPH. Some studies suggested misoprostol as an alternative treatment when Oxytocin isn't available.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0301211523008060

Effect of misoprostol versus oxytocin on delivery outcomes ... Meta-analysis revealed that vaginal misoprostol administration, compared with oxytocin, resulted in a significant reduction in the rate of cesarean.

9. aafp.org aafp.org/pubs/afp/issues/2021/0601/p656.html

Oxytocin as First-line Uterotonic Therapy for Postpartum ... Oxytocin therapy decreases the chances of a blood transfusion compared with misoprostol and has fewer adverse effects.