Oxytocin Rest for Prolonged Labor

(ORCA Trial)

Overseen By Teresa C Logue

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Christiana Care Health Services

Must be taking: Oxytocin

Disqualifiers: Intraamniotic infection, Eclampsia, 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: From randomization to delivery

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Prolonged labor is usually managed with continuous oxytocin infusion. "Oxytocin rest" has been proposed as a strategy to resolve protracted labor in patients who have received continuous oxytocin without progress. This strategy involves discontinuing oxytocin then restarting infusion after a period of time, under the theory that washout of the oxytocin receptor will strengthen uterine contractions to improve labor progress. "Oxytocin rest" is performed on labor and delivery units across the United States. Yet, there is no randomized or prospective data to support the practice. The purpose of this study is to assess whether oxytocin rest of 60 minutes in patients with prolonged labor reduces risk for cesarean delivery.

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 focuses on the use of oxytocin during labor, so it's best to discuss your specific medications with the trial team.

Is oxytocin safe for use in humans?

Oxytocin, including its synthetic forms like Syntocinon and Pitocin, has been used safely in many patients for labor-related purposes without observed side effects in some studies. However, misuse can lead to serious problems, so it should be used with proper supervision and dosage adjustment. ^{1 2 3 4 5}

How does the drug oxytocin differ from other treatments for prolonged labor?

Oxytocin is unique because it is a commonly used drug to help manage labor by stimulating uterine contractions, but its use requires careful supervision and dosage adjustment to avoid potential risks. Unlike some alternatives, oxytocin needs cold storage, which can be a challenge in low-resource settings. ^{1 4 6 7 8}

What data supports the effectiveness of the drug oxytocin for prolonged labor?

Research shows that synthetic oxytocin, like Pitocin, is commonly used in labor management and is considered as effective as natural oxytocin. However, its use requires careful supervision to avoid potential side effects, and there is no consensus on the optimal dose. ^{1 3 4 5 9}

Who Is on the Research Team?

Matthew Hoffman, MD

Principal Investigator

Christiana Care Health Services

Teresa C Logue

Principal Investigator

Christiana Care Health Services

Are You a Good Fit for This Trial?

This trial is for individuals experiencing prolonged labor or difficult childbirth, specifically when induction methods have failed. To participate, they must have been receiving continuous oxytocin without seeing progress in their labor.

Inclusion Criteria

Singleton gestation in vertex presentation

≥36 weeks gestation

My labor was slow, with less than 6cm dilation after 8 hours of my water breaking and being on oxytocin.

Exclusion Criteria

Not meeting the above criteria

Cesarean section anticipated by the clinical team at time of randomization (for any reason excepting labor dystocia)

I cannot receive oxytocin due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either 60-minute oxytocin rest or continuous oxytocin infusion to manage prolonged labor

From randomization to delivery

Continuous monitoring during labor

Follow-up

Participants are monitored for maternal and neonatal outcomes until hospital discharge

Up to 28 days for neonates, average of 3 days for mothers

What Are the Treatments Tested in This Trial?

Interventions

• Oxytocin

Trial Overview The study tests 'oxytocin rest,' which means stopping and then restarting oxytocin infusion after an hour to see if it reduces the need for cesarean delivery by improving uterine contractions and labor progress.

How Is the Trial Designed?

Group I: 60-minute oxytocin rest Experimental Treatment 1 Intervention

Group II: Usual care with continuous oxytocin infusion Active Control 1 Intervention

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?

Christiana Care Health Services

Lead Sponsor

Trials

118

Recruited

204,000+

Published Research Related to This Trial

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]

In a study of 57 women, 60% of those who were allowed to walk during labor delivered without the need for oxytocin, suggesting that ambulation may be an effective alternative for managing protracted labor.

Women in the ambulation group reported more positive experiences and had shorter second stages of labor, while those receiving oxytocin experienced stronger and more painful contractions, highlighting the potential benefits of allowing movement during labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ambulation versus oxytocin in protracted labour: a pilot study. Hemminki, E., Lenck, M., Saarikoski, S., et al.[2019]

The implementation of an evidence-based Pitocin administration checklist at a tertiary-level hospital significantly reduced the average duration of hospitalization from 2.02 days to 1.72 days, indicating improved efficiency in labor management.

The checklist also led to notable decreases in complications such as the presence of meconium (from 23.7% to 6.7%), maternal fevers (from 7.2% to 2.3%), and episiotomies (from 8.8% to 1.7%), suggesting enhanced safety and better birth outcomes for mothers and infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of the Evidence-Based Pitocin Administration Checklist at a Tertiary-Level Hospital. Wojnar, DM., Cowgill, K., Hoffman, L., et al.[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]

In a study of 20 first-time mothers, the combination of prostaglandin E(2) and oxytocin during labor induction significantly reduced the amount of oxytocin needed for effective uterine contractions.

The use of prostaglandin E(2) also shortened the duration of labor without any observed side effects, suggesting a safe and effective approach to labor induction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of labour by simultaneous intravenous administration of prostaglandin E 2 and oxytocin. Naismith, WC., Barr, W., MacVicar, J.[2019]

In a study of 2499 women undergoing cesarean sections, carbetocin significantly reduced moderate blood loss (>500 mL) and the need for additional uterotonics by 20% compared to oxytocin.

While carbetocin did not significantly lower the incidence of postpartum hemorrhage (≥1000 mL), it still provided a cost-effective option, resulting in a $63.46 reduction in costs per patient despite higher drug costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and financial evaluation of carbetocin as postpartum haemorrhage prophylaxis at caesarean section: A retrospective cohort study. Wohling, J., Edge, N., Pena-Leal, D., et al.[2020]

Heat-stable carbetocin is a promising alternative to oxytocin for preventing post-partum hemorrhage (PPH) in low-resource settings, as it does not require cold storage, addressing a major logistical challenge with oxytocin.

While carbetocin has a favorable side effect profile and potential additional benefits compared to oxytocin, its higher cost (20 times more) currently limits its use, although efforts are underway to make it more accessible in low- and middle-income countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbetocin: Worth the extra expense? Gallos, ID., Coomarasamy, A.[2020]

In a study of 490 women undergoing Cesarean delivery after oxytocin-augmented labor, a longer recovery interval from oxytocin infusion was linked to reduced estimated blood loss, suggesting that allowing time for oxytocin receptor recovery can improve outcomes.

Morbidly obese women experienced significantly higher blood loss compared to those with a lower body mass index, highlighting the need for careful management of oxytocin use and monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The association between the time from oxytocin cessation during labour to Cesarean delivery and postpartum blood loss: a retrospective cohort study. Tran, G., Kanczuk, M., Balki, M.[2018]

Citations

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

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

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

Synthetic oxytocin. [2018]

3. Ireland pubmed.ncbi.nlm.nih.gov

Ambulation versus oxytocin in protracted labour: a pilot study. [2019]

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

Outcomes of the Evidence-Based Pitocin Administration Checklist at a Tertiary-Level Hospital. [2018]

5. England pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Induction of labour by simultaneous intravenous administration of prostaglandin E 2 and oxytocin. [2019]

7. Australia pubmed.ncbi.nlm.nih.gov

Clinical and financial evaluation of carbetocin as postpartum haemorrhage prophylaxis at caesarean section: A retrospective cohort study. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Carbetocin: Worth the extra expense? [2020]

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

The association between the time from oxytocin cessation during labour to Cesarean delivery and postpartum blood loss: a retrospective cohort study. [2018]