Deuterated Oxytocin for Postpartum Hemorrhage

Recruiting at 1 trial location

Overseen By Somayeh Mohammadi

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Chicago

Disqualifiers: Allergy to oxytocin, others

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

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

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Oxytocin is the first-line drug to promote contraction of the uterus and prevent atony immediately after delivery. Nonetheless, unpredictable uterine atony refractory to oxytocin affects roughly 250,000 parturients annually in the U.S. and rates are increasing. This two-part study will measure the action of oxytocin at cesarean delivery. The first part will measure the pharmacokinetics of a single intravenous (IV) dose of deuterium-labeled oxytocin. The second part will measure the pharmacodynamics of all plasma oxytocin to see how concentrations correspond to the contractile effect on the uterus. After delivery of the fetus, study subjects will receive a bolus of IV deuterated oxytocin followed by an unlabeled oxytocin infusion. Venous blood samples drawn at multiple time points (within 1 hour after delivery) will be analyzed for plasma concentrations of labeled and unlabeled (endogenous + exogenous infused) oxytocin over time. Plasma concentrations will be compared with 0-10 uterine tone scores measuring uterine contraction strength, to describe the concentration-effect relationship. The goal of this study is to define both the pharmacokinetics and pharmacodynamics of oxytocin in parturients to help identify the cause(s) of failed first-line oxytocin therapy.

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 deuterated oxytocin safe for humans?

Oxytocin, which is similar to deuterated oxytocin, is generally used to prevent postpartum hemorrhage but can cause side effects, especially related to the heart and blood circulation. ^{1 2 3 4 5}

What makes Deuterated Oxytocin unique for treating postpartum hemorrhage?

Deuterated Oxytocin is a modified version of oxytocin, which is commonly used to prevent postpartum hemorrhage. This new version may offer improved stability or effectiveness, potentially addressing some of the limitations of regular oxytocin, especially in low-resource settings. ^{2 5 6 7 8}

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

Research shows that oxytocin, a component of Deuterated Oxytocin, is effective in preventing postpartum hemorrhage, which is a major cause of maternal death. Studies have demonstrated that oxytocin is commonly used and recommended for managing this condition, indicating its effectiveness in reducing bleeding after childbirth. ^{5 7 8 9 10}

Who Is on the Research Team?

Naida M Cole, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for pregnant women aged 18-50, at term (37+ weeks), undergoing a scheduled or unscheduled but non-emergent cesarean delivery. It's not suitable for those with an emergency c-section or allergy to oxytocin, or who cannot consent.

Inclusion Criteria

I am having a planned or unexpected C-section that's not an emergency.

Term pregnancy (>/= 37 weeks gestation)

Intrauterine pregnancy

Exclusion Criteria

Allergy to oxytocin

Emergent cesarean delivery

Inability to provide informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intraoperative Treatment

Participants receive a single bolus of deuterated oxytocin followed by an infusion of standard oxytocin immediately after placental delivery. Blood samples and uterine tone scores are collected intraoperatively.

1 hour

Intraoperative

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Deuterated Oxytocin

Trial Overview The study tests deuterated oxytocin (d5OT) to understand its pharmacokinetics and pharmacodynamics in preventing uterine atony after childbirth. Participants will receive d5OT intravenously post-delivery, followed by regular oxytocin, while their uterine contractions are monitored.

How Is the Trial Designed?

Group I: Oxytocin PK/PD Arm Experimental Treatment 1 Intervention

Eligible subjects will receive a single, 1 IU bolus of deuterated oxytocin (d5OT) intra-operatively, followed by an infusion of standard therapeutic d0 oxytocin immediately after placental delivery.

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Lucile Packard Children's Hospital

Collaborator

Trials

16

Recruited

2,800+

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]

In a study of 1000 women undergoing vaginal delivery, intravenous oxytocin significantly reduced mean total blood loss during the third stage of labor compared to saline, with an average reduction of 22%.

Oxytocin also decreased the rates of severe postpartum hemorrhage (>800 mL) and low postpartum hemoglobin (<10 g/dL) by approximately 40%, suggesting it is an effective and safe treatment for managing postpartum hemorrhage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine oxytocin in the third stage of labour: a placebo controlled randomised trial. Nordström, L., Fogelstam, K., Fridman, G., et al.[2019]

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 study of 343 women, administering oxytocin immediately after fetal delivery did not significantly reduce the incidence of postpartum hemorrhage compared to administration after placental delivery, with rates of 4.1% and 5.8% respectively.

The timing of oxytocin administration also did not affect the overall blood loss or other key outcomes, although it did result in a shorter duration of the third stage of labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intramuscular oxytocin administration before vs. after placental delivery for the prevention of postpartum hemorrhage: A randomized controlled prospective trial. Yildirim, D., Ozyurek, SE.[2018]

The introduction of a standardized oxytocin protocol (60 units over 5.25 hours) for postpartum hemorrhage (PPH) prophylaxis significantly reduced the rate of PPH treatment from 7.0% to 4.6% in a study of 16,811 women, indicating improved efficacy.

Among women identified as low risk for PPH, the protocol further decreased the treatment rate from 3.8% to 1.4%, suggesting that standardized higher doses of oxytocin can enhance safety and effectiveness in preventing PPH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Standardized Oxytocin Administration Protocol After Delivery to Reduce the Treatment of Postpartum Hemorrhage. Doyle, JL., Kenny, TH., Gothard, MD., et al.[2020]

In a review of 11,258 reports for oxytocin and 374 for carbetocin, carbetocin was associated with higher risks of hypertension, hypotension, and tachycardia compared to oxytocin, indicating potential safety concerns with its use.

Despite the increased reporting of adverse events for carbetocin, no deaths were linked to these events, while oxytocin-related tachycardia and bradycardia were associated with a small percentage of fatalities, suggesting that carbetocin may be safer in terms of severe outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An explorative analysis of pharmacovigilance data of oxytocin and its analogue carbetocin, with a focus on haemodynamic adverse effects. Stämpfli, D., Dommrich, R., Orbach-Zinger, S., et al.[2023]

In a study of 61 healthy pregnant women undergoing cesarean sections, both oxytocin and carbetocin showed similar effects on blood vessel dilation and blood pressure, but oxytocin caused a temporary drop in heart rate and sustained effects on heart function.

Carbetocin, while requiring more vasopressor support, did not lead to significant differences in uterine contraction effectiveness or bleeding compared to oxytocin, suggesting it may be a safer alternative with fewer cardiovascular side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular effects of oxytocin and carbetocin at cesarean section. A prospective double-blind randomized study using noninvasive pulse wave analysis. Rabow, S., Jonsson, H., Bro, E., et al.[2023]

The use of the Uniject device for administering oxytocin significantly reduced the incidence of postpartum hemorrhage (PPH) from 40.4% to 8.2% among 814 women, demonstrating its efficacy in preventing this serious condition.

The study, which compared 782 women with physiological management to those receiving active management of the third stage of labor (AMTL) over a period from March 1998 to May 2000, found that AMTL not only reduced PPH but was also well tolerated, suggesting it should be adopted in resource-poor settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postpartum hemorrhage: a prospective, comparative study in Angola using a new disposable device for oxytocin administration. Strand, RT., Da Silva, F., Jangsten, E., et al.[2018]

In a review of 61 randomized controlled trials involving 68,834 participants, oxytocin was found to significantly reduce the risk of side effects such as shivering, fever, and diarrhea compared to non-oxytocin treatments for preventing postpartum hemorrhage (PPH).

The study indicates that oxytocin does not increase the risk of other side effects during the third stage of labor, providing reassurance for its use in clinical settings by obstetricians and gynecologists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-effects of oxytocin in postpartum hemorrhage: a systematic review and meta-analysis. Zeng, Y., Zhang, Y., Zhen, M., et al.[2022]

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]

Citations

1. Portugal pubmed.ncbi.nlm.nih.gov

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

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

Routine oxytocin in the third stage of labour: a placebo controlled randomised trial. [2019]

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. Ireland pubmed.ncbi.nlm.nih.gov

Intramuscular oxytocin administration before vs. after placental delivery for the prevention of postpartum hemorrhage: A randomized controlled prospective trial. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A Standardized Oxytocin Administration Protocol After Delivery to Reduce the Treatment of Postpartum Hemorrhage. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

An explorative analysis of pharmacovigilance data of oxytocin and its analogue carbetocin, with a focus on haemodynamic adverse effects. [2023]

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

Cardiovascular effects of oxytocin and carbetocin at cesarean section. A prospective double-blind randomized study using noninvasive pulse wave analysis. [2023]

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

Postpartum hemorrhage: a prospective, comparative study in Angola using a new disposable device for oxytocin administration. [2018]

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

Side-effects of oxytocin in postpartum hemorrhage: a systematic review and meta-analysis. [2022]

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]