Oxytocin 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 be taking: Oxytocin

Disqualifiers: Hypertension, Cardiac disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 hours

40 Participants Needed

Trial Summary

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 oxytocin for postpartum hemorrhage?

Oxytocin is widely used as the standard treatment to prevent postpartum hemorrhage, which is a leading cause of maternal death. It is routinely administered after childbirth to help the uterus contract and reduce bleeding. ^{1 2 3 4 5}

Is oxytocin safe for use in humans?

Oxytocin, including its synthetic form Syntocinon, has been used safely in thousands of patients without observed side effects like vasospasm (narrowing of blood vessels) or anaphylactic reaction (severe allergic reaction). It is generally considered safe when used with proper supervision and dosage adjustment. ^{2 3 6 7 8}

How is the drug oxytocin unique in treating postpartum hemorrhage?

Oxytocin is unique because it is the most commonly used drug to prevent postpartum hemorrhage, and it can be administered both intravenously (through a vein) and intramuscularly (into a muscle), making it versatile for different settings, including emergencies and low-resource areas. ^{5 9 10 11 12}

What is the purpose of this trial?

This study is designed to determine the minimal effective oxytocin maintenance infusion required in labouring women undergoing cesarean delivery to achieve the best effect. Oxytocin is a drug that is routinely used to help the uterus to contract and keep it contracted after delivery. Consequently, it will help to reduce blood loss after delivery. In order to determine the minimal effective dose, the investigators will conduct a dose-finding study. The first patient will receive a set oxytocin infusion. The next patient's infusion dose of oxytocin, will either increase or decrease, depending on how the previous patient responds in terms of uterine tone. If the response is satisfactory with the infusion dose used, the next patient will either receive the same infusion dose or it will be decreased depending on a probability of 1:9. If the response is not satisfactory, then the infusion dose will increase for the next patient. The dose for each patient will be determined based on the results of the uterine contraction of the previous patient. The investigators hypothesize that the ED90 of the oxytocin infusion rate to maintain adequate uterine tone in labouring women with induced or augmented labour undergoing cesarean delivery, following an initial effective bolus dose, would be lower than 0.74 IU/min (44 IU/h), which was found as the ED90 in a previous study, without an initial bolus dose prior to the infusion.

Research Team

Mrinalini Balki, MD

Principal Investigator

MOUNT SINAI HOSPITAL

Eligibility Criteria

This trial is for women in labor who are having a cesarean delivery under neuraxial anesthesia and have been exposed to oxytocin for at least 3 hours. It's not suitable for those with hypertension, severe heart issues, allergies to oxytocin, contraindications to neuraxial anesthesia, or if general anesthesia becomes necessary during surgery.

Inclusion Criteria

I had labor induced or augmented and will have a cesarean with spinal or epidural anesthesia after at least 3 hours of oxytocin.

Exclusion Criteria

I refuse to sign the consent form for this trial.

All patients who declare allergy or hypersensitivity to oxytocin

I have a history of high blood pressure or serious heart conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive varying doses of oxytocin infusion to determine the minimal effective dose for maintaining uterine tone during cesarean delivery

2 hours

Intraoperative monitoring

Postoperative Monitoring

Participants are monitored for uterine tone and other physiological responses in the post anesthetic care unit (PACU)

2 hours

Continuous monitoring in PACU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood loss and need for additional uterotonic medication

24 hours

Treatment Details

Interventions

• Oxytocin

Trial Overview The study aims to find the lowest effective dose of oxytocin infusion needed after an initial bolus dose during cesarean delivery. The dosage will be adjusted up or down based on the previous patient's uterine response, aiming for better control of blood loss post-delivery.

Participant Groups

Group I: Oxytocin infusion rate 6 IU/h Experimental Treatment 1 Intervention

The maintenance infusion rate of oxytocin will be 6 IU/h.

Group II: Oxytocin infusion rate 4 IU/h Experimental Treatment 1 Intervention

The maintenance infusion rate of oxytocin will be 4 IU/h.

Group III: Oxytocin infusion rate 36 IU/h Experimental Treatment 1 Intervention

The maintenance infusion rate of oxytocin will be 36 IU/h.

Group IV: Oxytocin infusion rate 34 IU/h Experimental Treatment 1 Intervention

The maintenance infusion rate of oxytocin will be 34 IU/h.

Group V: Oxytocin infusion rate 30 IU/h Experimental Treatment 1 Intervention

The maintenance infusion rate of oxytocin will be 30 IU/h.

Group VI: Oxytocin infusion rate 26 IU/h Experimental Treatment 1 Intervention

The maintenance infusion rate of oxytocin will be 26 IU/h.

Group VII: Oxytocin infusion rate 22 IU/h Experimental Treatment 1 Intervention

The maintenance infusion rate of oxytocin will be 22 IU/h.

Group VIII: Oxytocin infusion rate 18 IU/h Experimental Treatment 1 Intervention

The maintenance infusion rate of oxytocin will be 18 IU/h.

Group IX: Oxytocin infusion rate 14 IU/h Experimental Treatment 1 Intervention

The maintenance infusion rate of oxytocin will be 14 IU/h.

Group X: Oxytocin infusion rate 10 IU/h Experimental Treatment 1 Intervention

The maintenance infusion rate of oxytocin will be 10 IU/h.

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?

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Lead Sponsor

Trials

132

Recruited

11,400+

Findings from Research

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 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]

In a systematic review of 24 studies involving 37,383 patients, carbetocin was found to be more effective than oxytocin in reducing postpartum hemorrhage (PPH) and the need for additional uterine contractions in both cesarean and vaginal deliveries.

Carbetocin also showed a lower incidence of headaches compared to oxytocin in cesarean section patients, while both drugs had similar safety profiles regarding other side effects, suggesting that carbetocin is a promising alternative for preventing PPH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of carboxytocin versus oxytocin in preventing postpartum hemorrhage: A systematic review and meta-analysis. Sun, H., Xu, L., Li, Y., et al.[2022]

In a large trial involving 29,645 women, heat-stable carbetocin was found to be noninferior to oxytocin in preventing significant blood loss (≥500 ml) after vaginal birth, with similar rates of additional uterotonic use between the two groups.

However, carbetocin did not demonstrate noninferiority for blood loss of ≥1000 ml, indicating that while it is a viable alternative to oxytocin, further studies may be needed to confirm its effectiveness for more severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth. Widmer, M., Piaggio, G., Nguyen, TMH., et al.[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]

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]

Carbetocin is as effective as syntometrine in preventing primary postpartum hemorrhage, with no significant difference in hemoglobin drop or the need for additional oxytocic injections among 329 women studied.

Carbetocin has a lower incidence of adverse effects such as nausea, vomiting, and hypertension compared to syntometrine, making it a safer alternative for managing the third stage of labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised trial of carbetocin versus syntometrine in the management of the third stage of labour. Leung, SW., Ng, PS., Wong, WY., et al.[2021]

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 survey of 391 obstetricians and anesthesiologists in Israel revealed significant variability in their practices regarding oxytocin administration for preventing post-partum hemorrhage, particularly between the two groups during primary cesarean sections.

Both groups tended to use high doses of oxytocin (5 or 10 units IV bolus), indicating a need for national guidelines to standardize practices and enhance patient safety by potentially reducing the risk associated with high bolus dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A survey of physicians' attitudes toward uterotonic administration in parturients undergoing cesarean section. Orbach-Zinger, S., Einav, S., Yona, A., et al.[2019]

In a study of 927 women undergoing planned cesarean sections, those receiving 2.5 IU of oxytocin experienced slightly higher peroperative blood loss compared to those receiving 5.0 IU (476 ml vs 426 ml), indicating that the higher dose may be more effective in minimizing blood loss.

While the 2.5 IU group had a higher percentage of women with significant blood loss (≥ 1000 ml), it was deemed a safe option for women without known risk factors for postpartum hemorrhage, suggesting that lower doses may be appropriate in certain cases, but further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risk of postpartum hemorrhage when lowering the oxytocin dose in planned cesarean section, a pilot study. Stålberg, V., Josefsson, A., Bladh, M., et al.[2021]

In a study of 216 unplanned out-of-hospital deliveries in Finland, the use of oxytocin did not show a significant reduction in postpartum hemorrhage compared to cases where it was not used, indicating that it may not be essential for all ambulance units.

The study found no differences in secondary outcomes, such as hemoglobin levels and the need for additional medical interventions, between deliveries with and without oxytocin, suggesting that its effectiveness in emergency settings may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of oxytocin in prevention of postpartum hemorrhage in unplanned out-of-hospital deliveries treated by emergency medical services. Klemettilä, E., Rahkonen, L., Nuutila, M., et al.[2020]

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

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

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

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

3. Australia pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of carboxytocin versus oxytocin in preventing postpartum hemorrhage: A systematic review and meta-analysis. [2022]

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

Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth. [2022]

5. Portugal pubmed.ncbi.nlm.nih.gov

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

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

Synthetic oxytocin. [2018]

7. England pubmed.ncbi.nlm.nih.gov

A randomised trial of carbetocin versus syntometrine in the management of the third stage of labour. [2021]

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

Carbetocin for the prevention of postpartum hemorrhage: a systematic review. [2018]

9. England pubmed.ncbi.nlm.nih.gov

A survey of physicians' attitudes toward uterotonic administration in parturients undergoing cesarean section. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

The risk of postpartum hemorrhage when lowering the oxytocin dose in planned cesarean section, a pilot study. [2021]

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

Role of oxytocin in prevention of postpartum hemorrhage in unplanned out-of-hospital deliveries treated by emergency medical services. [2020]

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

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