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

Neonatal Morbidity Clinical Trial

— STOPOXY  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03991091
• Other study ID #: P180581
• Status: Completed
• Phase: Phase 4
• Start date: January 17, 2020
• Est. completion date: April 25, 2022

Study information

• Verified date: October 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2459
• Est. completion date: April 25, 2022
• Est. primary completion date: April 25, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• 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.
• continuation of oxytocin administration
continuation of oxytocin administration

Locations

Country	Name	City	State
France	hospital Cochin; port royal Maternity unit	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	umbilical cord pH<7.20	umbilical arterial cord pH at birth less than 7.20	At birth
Secondary	umbilical cord pH<7.10	umbilical arterial cord pH at birth less than 7.10	At birth
Secondary	umbilical cord pH<7.00	umbilical arterial cord pH at birth less than 7.00	At birth
Secondary	Need for hypothermia	need for hypothermia	At birth
Secondary	other neonatal complications:	need of resuscitation at birth	2 hours postpartum
Secondary	neonatal admission	transfer to neonatal care unit	2 hours postpartum
Secondary	length of the newborn's hospital stay	length of hospital stay	0-1 month
Secondary	mode of delivery	cesarean rate	0-48hours
Secondary	mode of delivery	cesarean rate for abnormal fetal heart rate	0-48hours
Secondary	mode of delivery	instrumental vaginal delivery	0-48hours
Secondary	mode of delivery	instrumental delivery for abnormal fetal heart rate	0-48hours
Secondary	labor duration	labor duration (active 1st stage, passive and active 2nd stage)	0-48hours
Secondary	uterine hyper-stimulation	uterine hyper-stimulation, defined by periods with more than 5 uterine contractions in 10 minutes during labor	0-48hours
Secondary	fetal scalp blood testing	need for fetal scalp blood testing during labor	0-48hours
Secondary	fetal occipito-posterior position	fetal occipito-posterior position	0-48hours
Secondary	maternal hyperthermia	maternal fever during labor, defined by maternal temperature >38°C	0-48hours
Secondary	postpartum hemorrhage	post-partum hemorrhage, defined by an estimated blood loss >500mL	0-48hours
Secondary	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
Secondary	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
Secondary	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
Secondary	The post-partum women's satisfaction	Satisfactiuon of labor and childbirth with Labor Agentry Scale	at 2 months postpartum in a survey
Secondary	The post-partum women's satisfaction	Birth experience and well being with EPDS at 2 months	at 2 months postpartum in a survey
Secondary	The post-partum women's satisfaction	Breastfeeding at 2 months	at 2 months postpartum in a survey