Clinical trial NCT03991091: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neonatal Morbidity
Keywords: Multicenter
randomized
control study
Oxytocin discontinuation
Neonatal acidosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2019-06-19
Enrollment: 2459
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: neonatal morbidity composite measure
timeFrame: At birth
Secondary outcomes:
measure: umbilical cord pH<7.20
timeFrame: At birth
measure: umbilical cord pH<7.10
timeFrame: At birth
measure: umbilical cord pH<7.00
timeFrame: At birth
measure: Need for hypothermia
timeFrame: At birth
measure: other neonatal complications:
timeFrame: 2 hours postpartum
measure: neonatal admission
timeFrame: 2 hours postpartum
measure: length of the newborn's hospital stay
timeFrame: 0-1 month
measure: mode of delivery
timeFrame: 0-48hours
measure: mode of delivery
timeFrame: 0-48hours
measure: mode of delivery
timeFrame: 0-48hours
measure: mode of delivery
timeFrame: 0-48hours
measure: labor duration
timeFrame: 0-48hours
measure: uterine hyper-stimulation
timeFrame: 0-48hours
measure: fetal scalp blood testing
timeFrame: 0-48hours
measure: fetal occipito-posterior position
timeFrame: 0-48hours
measure: maternal hyperthermia
timeFrame: 0-48hours
measure: postpartum hemorrhage
timeFrame: 0-48hours
measure: The post-partum women's satisfaction
timeFrame: 0 5 day
measure: The post-partum women's satisfaction: labor agentry scale
timeFrame: at 2 months postpartum in a survey
measure: The post-partum women's satisfaction
timeFrame: at 2 months postpartum in a survey
measure: The post-partum women's satisfaction
timeFrame: at 2 months postpartum in a survey
measure: The post-partum women's satisfaction
timeFrame: at 2 months postpartum in a survey
measure: The post-partum women's satisfaction
timeFrame: at 2 months postpartum in a survey
Other outcomes:
Locations:
city: Paris
country: France
facility: hospital Cochin; port royal Maternity unit
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Camille Le Ray, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.