Reducing Neonatal Morbidity by Discontinuing Oxytocin During the Active Phase of 1st Stage of Labor (STOPOXY)

Reducing Neonatal Morbidity by Discontinuing Oxytocin During the Active Phase of 1st Stage of Labor: a Multicenter Randomized Controlled Trial

The purpose of this study is to measure the impact of a discontinuous administration of oxytocin during the active phase of the 1st stage of labor on the neonatal morbidity rate.

The investigators hypothesize that discontinuation of oxytocin in the active phase of labor (from 6 cm) in women who received oxytocin in the latent phase or for an induction (before 4 cm of dilation) could reduce neonatal morbidity.

Study Overview

• Status: Completed
• Conditions: Neonatal Morbidity
• Intervention / Treatment: Drug: discontinuation of oxytocin administration; Drug: continuation of oxytocin administration

Detailed Description

Oxytocin is effective in increasing frequency and intensity of uterine contractions and therefore in reducing the duration of labor. Nevertheless, its administration is potentially associated with fetal and maternal short-and long- term complications, such as neonatal acidosis and post-partum hemorrhage and its effectiveness in decreasing caesarean section rate has not been clearly demonstrated.

The most important side effect of oxytocin infusion is uterine hyper-stimulation, which has been shown to occur in more than 30% of women induced with oxytocin. By causing uterine hyper-stimulation, oxytocin infusion may lead to or aggravate abnormal fetal heart rate, contributing to neonatal acidosis. Acidosis is a major part of neonatal morbidity due to related complications such as hospitalization in neonatal intensive care units, but also neonatal death or cerebral palsy in the most severe cases.

The first stage of labor is divided into two phases, a latent phase where cervical dilation is relatively slow until 5-6 cm and an active phase until full dilatation, where cervical dilation accelerates. Currently in France, when oxytocin administration has been initiated during the latent phase, the standard care is to continue it during the whole duration of labor. One assumption is that, once women requiring oxytocin during the latent phase enter the active phase, natural oxytocin takes over from synthetic oxytocin. Thus, in the active phase, oxytocin could be discontinued, reducing exposure duration and therefore reducing the risk of complications, in particular neonatal complications, without compromising the chances of vaginal delivery.

It can therefore be hypothesized that discontinuation of oxytocin in the active phase of labor (from 6 cm) in women who received oxytocin in the latent phase or for an induction (before 4 cm of dilation) could reduce neonatal morbidity.

Several small trials attempting to evaluate this practice have been published, but their design and small population did not allow evaluating the impact of discontinuation of oxytocin on neonatal morbidity. Thus, the investigators propose to conduct a large randomized controlled trial, STOPOXY, aiming to reduce oxytocin exposure and its adverse effects.

The investigators expect an improvement of child health at birth, with less severe neonatal morbidity that may cause neurologic damages and less moderate neonatal morbidity that may be associated with the need of resuscitation and hospitalization.

The investigators plan to conduct a multicenter, randomized, open-label, controlled trial comparing neonatal and maternal outcomes among term singleton neonates after discontinuation or continuation of oxytocin infusion during the active phase of the 1st stage of labor.

Two arms:

• Experimental group: discontinuation of oxytocin administration at the beginning of the active phase of the 1st stage of labor, i.e. oxytocin infusion will be stopped beyond a cervical dilatation of 6cm. In the experimental group, oxytocin can be re-started, if necessary, after 2 hours of arrest of labor.
• Control group: standard care in France, i.e. when oxytocin is started during the latent phase of the 1st stage, administration of oxytocin is continued during the active 1st stage and during the 2nd stage if the fetal heart rate is reassuring.

The open-label design was chosen for several reasons. The main reason is that in case of a blinded trial, the need for un-blinding would be too frequent as the investigators estimate it from the previous published trials at 30 to 40%. The second reason is feasibility. Indeed, in case of non-reassuring fetal heart rate, it is important for the obstetrician to be able to stop the oxytocin infusion to reduce the uterine contractility.

• Study Type: Interventional
• Enrollment (Actual): 2459
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • hospital Cochin; port royal Maternity unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• With a term (≥37 WG) pregnancy
• Singleton pregnancy
• Fetus in cephalic presentation
• Women receiving oxytocin during the latent phase of the 1st stage of labor, before 4 cm of cervical dilatation, including women with an induction of labor using cervical ripening or oxytocin
• Speaking and reading French language
• Affiliated to social security
• Who have signed the consent form

Exclusion Criteria:

• Women with a scarred uterus
• Fetus with a congenital anomaly
• Fetal growth retardation <3rd percentile
• Having an abnormal fetal heart rate at randomization
• Maternal age < 18 years
• Participating in another trial involving medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: discontinuation of oxytocin administration; Discontinuation of oxytocin administration at the beginning of the active phase of the 1st stage of labor, i.e. oxytocin infusion will be stopped beyond a cervical dilatation of 6cm	Drug: discontinuation of oxytocin administration; Discontinuation of oxytocin administration at the beginning of the active phase of the 1st stage of labor, i.e. oxytocin infusion will be stopped beyond a cervical dilatation of 6cm. In the experimental group, oxytocin can be re-started, if necessary, after 2 hours of arrest of labor.
Active Comparator: continuation of oxytocin administration; Standard care in France, i.e. when oxytocin is started during the latent phase of the 1st stage, administration of oxytocin is continued during the active 1st stage and during the 2nd stage if the fetal heart rate is reassuring.	Drug: continuation of oxytocin administration; continuation of oxytocin administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
neonatal morbidity composite measure	Neonatal morbidity will be assessed using a composite variable defined by: an umbilical arterial pH at birth <7.10 and/or a base excess >10mmol/L and/or umbilical arterial lactates>7 mmol/L and/or a 5 minutes Apgar score <7 and/or admission in neonatal intensive care unit (NICU). This composite outcome is based on pertinent and previously published thresholds to assess neonatal acidosis[16]	At birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
umbilical cord pH<7.20	umbilical arterial cord pH at birth less than 7.20	At birth
umbilical cord pH<7.10	umbilical arterial cord pH at birth less than 7.10	At birth
umbilical cord pH<7.00	umbilical arterial cord pH at birth less than 7.00	At birth
Need for hypothermia	need for hypothermia	At birth
other neonatal complications:	need of resuscitation at birth	2 hours postpartum
neonatal admission	transfer to neonatal care unit	2 hours postpartum
length of the newborn's hospital stay	length of hospital stay	0-1 month
mode of delivery	cesarean rate	0-48hours
mode of delivery	cesarean rate for abnormal fetal heart rate	0-48hours
mode of delivery	instrumental vaginal delivery	0-48hours
mode of delivery	instrumental delivery for abnormal fetal heart rate	0-48hours
labor duration	labor duration (active 1st stage, passive and active 2nd stage)	0-48hours
uterine hyper-stimulation	uterine hyper-stimulation, defined by periods with more than 5 uterine contractions in 10 minutes during labor	0-48hours
fetal scalp blood testing	need for fetal scalp blood testing during labor	0-48hours
fetal occipito-posterior position	fetal occipito-posterior position	0-48hours
maternal hyperthermia	maternal fever during labor, defined by maternal temperature >38°C	0-48hours
postpartum hemorrhage	post-partum hemorrhage, defined by an estimated blood loss >500mL	0-48hours
The post-partum women's satisfaction	women's satisfaction is recorded using the "labor agentry scale". Scores on the Labor Agentry Scale range from 29 to 203, with higher scores indicating greater perceived control during childbirth.	0 5 day
The post-partum women's satisfaction: labor agentry scale	women's satisfaction is recorded using the "labor agentry scale"[18]	at 2 months postpartum in a survey
The post-partum women's satisfaction	Edinburgh Postnatal Depression Scale. Scores on the Edinburgh Postnatal Depression Scale rabge from 0 to 30, with higher score indicating mental health issues.	at 2 months postpartum in a survey
The post-partum women's satisfaction	Satisfactiuon of labor and childbirth with Labor Agentry Scale	at 2 months postpartum in a survey
The post-partum women's satisfaction	Birth experience and well being with EPDS at 2 months	at 2 months postpartum in a survey
The post-partum women's satisfaction	Breastfeeding at 2 months	at 2 months postpartum in a survey

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; URC-CIC Paris Descartes Necker Cochin
• Investigators: Principal Investigator: Camille Le Ray, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Girault A, Sentilhes L, Desbriere R, Berveiller P, Korb D, Bertholdt C, Carrara J, Winer N, Verspyck E, Boudier E, Barjat T, Levy G, Roth GE, Kayem G, Massoud M, Bohec C, Guerby P, Azria E, Blanc J, Heckenroth H, Rousseau J, Garabedian C, Le Ray C; collaborators of the STOPOXY trial and the Groupe de Recherche en Obstetrique et Gynecologie (GROG). Impact of discontinuing oxytocin in active labour on neonatal morbidity: an open-label, multicentre, randomised trial. Lancet. 2023 Dec 2;402(10417):2091-2100. doi: 10.1016/S0140-6736(23)01803-2. Epub 2023 Nov 9.
• Girault A, Goffinet F, Le Ray C; collaborators of the STOPOXY trial and the Groupe de Recherche en Obstetrique et Gynecologie (GROG). Reducing neonatal morbidity by discontinuing oxytocin during the active phase of first stage of labor: a multicenter randomized controlled trial STOPOXY. BMC Pregnancy Childbirth. 2020 Oct 20;20(1):640. doi: 10.1186/s12884-020-03331-x.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2020
• Primary Completion (Actual): April 25, 2022
• Study Completion (Actual): April 25, 2022

Study Registration Dates

• First Submitted: May 24, 2019
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (Actual): June 19, 2019

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: randomized; Multicenter; control study; Oxytocin discontinuation; Neonatal acidosis
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: APHP180581

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No