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

Trial Summary

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.

What data supports the effectiveness of the drug oxytocin for reducing bleeding?

Research shows that oxytocin is a commonly used drug to prevent postpartum hemorrhage (heavy bleeding after childbirth) and is considered the first-line treatment in the United States for this purpose. It is often used in combination with other drugs to enhance its effectiveness in preventing excessive bleeding. ^{1 2 3 4 5}

How is the drug oxytocin unique in reducing bleeding?

Oxytocin is unique because it is a commonly used uterotonic agent (a drug that induces contraction of the uterus) to prevent postpartum hemorrhage, but there is no established standard dose, and its administration varies widely. It is particularly recommended in low-resource settings despite challenges, and it is considered effective with minimal side effects when used under proper supervision. ^{1 2 6 7 8}

What is the purpose of this trial?

The purpose of this study is to assess the effectiveness of prophylactic oxytocin on hemorrhage rates for second trimester dilation and evacuation (D\&E) in the clinic setting.

Eligibility Criteria

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

I refuse to receive treatments through an IV.

Multiple gestation

I have used blood thinners in the last 5 days.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Carbetocin versus oxytocin for prevention of postpartum hemorrhage in hypertensive women undergoing elective cesarean section. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Variations in oxytocin regimes in Scottish labour wards in 1998. [2004]

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

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

4. England 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. [2023]

5. India pubmed.ncbi.nlm.nih.gov

Evaluation of in vivo effects of Oxytocin on coagulation of parturient during cesarean delivery by thromboelastography. [2021]

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

Synthetic oxytocin. [2018]

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

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

8. Portugal pubmed.ncbi.nlm.nih.gov

[The Role of Oxytocin in the Prevention of Postpartum Hemorrhage in Low-Resource Settings]. [2022]