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

• ClinicalTrials.gov Identifier: NCT03991091
• Recruitment Status: Completed
• First Posted: June 19, 2019
• Last Update Posted: November 1, 2022
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Institut National de la Santé Et de la Recherche Médicale, France
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: May 24, 2019
• First Posted Date: June 19, 2019
• Last Update Posted Date: November 1, 2022
• Actual Study Start Date: January 17, 2020
• Actual Primary Completion Date: April 25, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 18, 2019)

neonatal morbidity composite measure [ Time Frame: At birth ]

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]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 18, 2019)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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.

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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neonatal Morbidity

Intervention

• 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.
• Drug: continuation of oxytocin administration
  continuation of oxytocin administration

Study Arms

• 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
  Intervention: Drug: discontinuation of oxytocin administration
• 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.
  Intervention: Drug: continuation of oxytocin administration

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 18, 2019): 2475
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 25, 2022
• Actual Primary Completion Date: April 25, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT03991091
• Other Study ID Numbers: P180581
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Same as current
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France

Investigators

• Principal Investigator: Camille Le Ray, MD, PhD; Assistance Publique - Hôpitaux de Paris

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: October 2022