Oxytocin for Reducing Bleeding

Overseen By Megan Masten, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Anticoagulants, Misoprostol

Disqualifiers: Coagulopathy, Sepsis, Placenta accreta, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests oxytocin's effectiveness in reducing bleeding during dilation and evacuation (D&E) in the second trimester of pregnancy. The goal is to determine if oxytocin lowers the risk of hemorrhage (severe bleeding) compared to a placebo (a harmless substance with no medical effect). Suitable participants should plan to undergo a D&E at 18 weeks of pregnancy or later and should not have blood clotting issues or infections. Participants will receive either oxytocin (a hormone used to induce labor) mixed in a saline solution or just the saline, and the effects will be compared. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've used anticoagulants (blood thinners) in the five days before the trial.

Is there any evidence suggesting that oxytocin is likely to be safe for humans?

Research shows that oxytocin is generally safe when used correctly. The FDA has approved it to assist with labor and control bleeding after childbirth, indicating its safe use by many people. However, improper use can lead to side effects. Administering oxytocin correctly is crucial to avoid complications.

Reports indicate that incorrect use can be harmful, such as causing excessive uterine contractions, which can be dangerous. However, when given in the right dose and setting, it is usually well-tolerated.

In summary, oxytocin has been safely used for many years, particularly in childbirth. When administered carefully, the risk of serious side effects remains low. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for reducing bleeding during dilation and evacuation (D&E) procedures involve medications like misoprostol or methylergometrine, which work by contracting the uterus. Unlike these, oxytocin is unique because it is a natural hormone that effectively stimulates uterine contractions, potentially reducing bleeding more directly and safely. Researchers are excited about oxytocin because it is already widely used in childbirth for similar purposes, suggesting it could be a safer and more familiar option for clinicians. Additionally, its IV administration during D&E allows for immediate action, which could lead to better management of bleeding and improved patient outcomes.

What evidence suggests that oxytocin might be an effective treatment for reducing bleeding?

Research has shown that oxytocin, which participants in this trial may receive, can help reduce blood loss. In studies, oxytocin lowered blood loss by about 81 mL on average. This finding was observed in eleven different trials with over 7,800 participants. Oxytocin is often used to prevent heavy bleeding after childbirth and has proven effective in reducing bleeding rates. Overall, this suggests that oxytocin might also help reduce bleeding in other medical procedures, such as dilation and evacuation (D&E). ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals undergoing a clinic-based dilation and evacuation (D&E) procedure at or beyond 18 weeks of pregnancy. Participants must be able to communicate in either English or Spanish.

Inclusion Criteria

I am over 18 weeks pregnant and can visit a clinic for check-ups.

Exclusion Criteria

Multiple gestation

I refuse to receive treatments through an IV.

I have used blood thinners in the last 5 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either 40 units IV oxytocin in 1000 mL of normal saline or 1000 mL of normal saline alone at the time of tenaculum placement for D&E

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of hemorrhage and patient satisfaction

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oxytocin

Trial Overview The study is testing whether giving oxytocin mixed with normal saline before the D&E can reduce bleeding compared to just normal saline. It's designed to see if this approach is effective in preventing hemorrhage during the second trimester D&E procedures.

How Is the Trial Designed?

Group I: Oxytocin Experimental Treatment 1 Intervention

Participants receive 40 units IV oxytocin in 1000 mL of normal saline at the time of tenaculum placement for D\&E.

Group II: Placebo Placebo Group 1 Intervention

Participants receive 1000 mL of normal saline alone at the time of tenaculum placement for D\&E.

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

Approved in United States as Pitocin for:

• Induction of labor
• Augmentation of labor
• Control of postpartum bleeding

Approved in European Union as Syntocinon for:

• Induction of labor
• Augmentation of labor
• Control of postpartum bleeding

Approved in Canada as Oxytocin for:

• Induction of labor
• Augmentation of labor
• Control of postpartum bleeding

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

Oxytocin is the preferred treatment for preventing postpartum hemorrhage, but its effectiveness in low-resource settings is hindered by issues such as a lack of trained healthcare professionals and poor drug quality, as highlighted in a review of 24 articles.

To effectively reduce maternal mortality from postpartum hemorrhage in these settings, it is crucial to enhance healthcare training, improve drug management practices, and address cultural barriers that limit access to necessary health services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Role of Oxytocin in the Prevention of Postpartum Hemorrhage in Low-Resource Settings]. Ferreira, I., Reynolds, A.[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 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]

Mixing certain oxytocin and tranexamic acid injection products can lead to a significant reduction in oxytocin concentration (14.8%-29.0%) immediately after mixing, which could compromise patient care during emergencies.

Due to the observed interactions that may result in underdosing of oxytocin, it is recommended to avoid mixing these two medications for intravenous infusion until further research clarifies the implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The compatibility of oxytocin and tranexamic acid injection products when mixed for co-administration by infusion for the treatment of postpartum haemorrhage: An in vitro investigation. Lambert, P., Tomazzini, A., Wright, P., et al.[2023]

Oxytocin is widely used to augment labor in low-risk first-time mothers, with a survey indicating that 38% of such labors in the UK are treated with intravenous syntocinon.

There is significant variation in the dosing and administration of syntocinon across Scottish obstetric units, which raises concerns about potential risks to both mothers and fetuses due to misuse, highlighting the need for standardized guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variations in oxytocin regimes in Scottish labour wards in 1998. Arnott, N., Harrold, AJ., Lynch, P.[2004]

Syntocinon(R), a synthetic form of oxytocin, was found to be as effective as natural oxytocin in a study involving 3,342 obstetrical patients.

The use of Syntocinon(R) showed no significant side effects, such as vasospasm or anaphylactic reactions, suggesting it is safe for clinical use in obstetrics when properly indicated and monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthetic oxytocin. HIBBARD, LT., ANDREWS, AV.[2018]

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 a study involving 84 healthy parturient women, increasing the infusion rate of oxytocin from 15 IU/h to 30 IU/h significantly enhanced coagulation parameters, indicating a higher coagulability during cesarean delivery.

The findings suggest that a faster infusion rate of oxytocin (30 IU/h) can lead to a modest hypercoagulable state, which may have implications for managing bleeding risks during and after cesarean sections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of in vivo effects of Oxytocin on coagulation of parturient during cesarean delivery by thromboelastography. Golparvar, M., Esterabi, M., Talakoub, R., et al.[2021]

Citations

1. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.18279

The Effectiveness of Oxytocin for Preventing Postpartum ... Analysis of all data suggested that oxytocin use significantly decreased EBL by 81 mL (11 RCTs, n = 7814, MD −80.89; 95% CI −115.21 to −46.57, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3282278/

Higher-Dose Oxytocin and Hemorrhage After Vaginal ... Overall, the primary composite outcome of treatment for hemorrhage or atony occurred in 6–7% of the study sample. Compared to the 10U group, higher doses of ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002937825000651

Association of postpartum oxytocin dose and ... High-dose postpartum oxytocin was associated with lower rates of postpartum hemorrhage than lower oxytocin doses. Results appeared consistent for both vaginal ...

4. ajog.org ajog.org/article/S0002-9378(22)02204-9/fulltext

Third stage of labor: evidence-based practice for ... Among all deliveries, there were 3 strategies more effective than oxytocin alone in reducing blood loss ≥500 mL: ergometrine plus oxytocin ...

5. academic.oup.com academic.oup.com/milmed/advance-article/doi/10.1093/milmed/usae545/8051099

Low-Dose Oxytocin Protocol Decreases Quantitative Blood ... The prophylactic use of oxytocin has been shown to reduce blood loss after delivery by 40 to 50%.1–5 The dose of oxytocin given after cesarean ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK507848/

Oxytocin - StatPearls - NCBI Bookshelf - NIH Oxytocin is FDA-approved for use in the antepartum and postpartum periods to facilitate labor and control postpartum hemorrhage.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2014/018261s031lbl.pdf

Pitocin - accessdata.fda.gov Since the available data are inadequate to evaluate the benefits-to-risks considerations, Pitocin is not indicated for elective induction of labor. Antepartum: ...

8. ajog.org ajog.org/article/S0002-9378(23)00439-8/fulltext

Oxytocin: physiology, pharmacology, and clinical ... Used in error, oxytocin can cause patient harm, highlighting the importance of precise administration using infusion pumps, institutional safety ...

9. reference.medscape.com reference.medscape.com/drug/pitocin-oxytocin-343132

Pitocin (oxytocin) dosing, indications, interactions, adverse ... Because the available data are inadequate to evaluate the benefits-to-risks onsiderations, oxytocin is not indicated for elective induction of labor.

10. mayoclinic.org mayoclinic.org/drugs-supplements/oxytocin-intravenous-route-intramuscular-route/description/drg-20065254

Oxytocin (intravenous route, intramuscular route) Oxytocin can be very useful for helping labor. However, there are certain risks with using it. Oxytocin causes contractions of the uterus. In ...