Comparison of Two Rhythm of Administration of Prostaglandin Gel for Induction of Labor (GELFREQ)

Administration of Prostaglandin Gel for Cervical Priming During Induction of Labour Every 12 Hours Versus 24 Hours: a Randomized Superiority Controlled Trial

The study compares two rhythms of administration of prostaglandin vaginal gels for cervical priming before induction of labor in term patients. In our institution, prostaglandin gels are given for a maximum of three times, with induction by oxytocin and amniotomy the day after the last gel whatever Bishop score has been obtained. This management results in some patient spending four days in hospital before delivery. The aim of the study is to compare our classical management scheme with a reduced interval between to gels, of 12h instead of 24 h. The primary outcome will be the time elapsed between the first prostaglandin gel and delivery. Tolerance of both management patterns will also be evaluated through a satisfaction survey.

Study Overview

• Status: Completed
• Conditions: Labor Complication; Cervix
• Intervention / Treatment: Drug: Dinoprostone vaginal gel

Detailed Description

Approximatively 22% of pregnant women have an induction of labor in France (22.9% in our institution in 2019), mainly for prolonged pregnancy after 41 weeks gestational age or prolonged rupture of membranes. Patients whose cervix is considered unripe (Bishop score under 6) are generally proposed a cervical priming because induction of labor without prior priming entails a higher of cesarean delivery rate for failed induction. The devices used for cervical priming are pharmacological (mainly prostaglandin gel, pessaries or suppositories) or mechanical (Foley catheter, Cook balloons). Very few recommendations exist regarding the type of device, the rhythm and maximal number of repeat administrations and the interval between two administrations. Shortening interval between two administrations (in case of use of a device necessitating serial prescriptions) may shorten the time interval between beginning of priming and delivery. In our institution, a vaginal gel can be given three times before induction of labor with oxytocin and amniotomy, whatever Bishop score has been obtained after priming. These gels are given on a daily basis. This rhythm implies than for some women not responding to a first gel, priming can last up to three days, lengthening hospital stay and leading to maternal weariness. Maternal satisfaction during induction of labor is seldom analyzed. An intensification in gel administration implies a change in maternal management during the induction process, with shortened periods of rest between two gels and nearer periods of pain and discomfort, albeit on a theoretically shorter period. The way patients deal with this new rhythm compared to the classical in part of the evaluation in this study. All patients having a singleton pregnancy and an indication for term (≥ 37 weeks gestation age) induction with an unfavorable cervix and no contraindication to vaginal delivery will be eligible. Patients with fetuses in breech presentation, a scarred uterus, under 18 years, bearing a fetus with antenatally known malformation, not fluent in French or presenting an allergy to prostaglandins will be excluded. A written informed consent will be required before inclusion. The primary outcome will be the duration between first priming with prostaglandin gel and delivery. Secondary outcomes will be the satisfaction of patients with their induction process (measured through a survey answered during the in-hospital post-partum stay), the rate of cesarean section, the rate of hypertonia/hypercinesia during priming and induction requiring medical intervention, the length of active phase of labor (after 5 cm of dilation), the oxytocin doses used during delivery for induction or augmentation, initial neonatal (Apgar score, arterial cord pH and lactates, resuscitation maneuvers, transfer to intensive care unit) and maternal (post-partum hemorrhage, hyperthermia during labor, perineal laceration > 2nd degree and endometritis) morbidity and length of total hospital stay. The investigators calculated that a sample of 268 patients (134 in each group) will be necessary to detect a 30% reduction in duration between first priming and delivery in the experimental group (one gel every 12h) compared with the classical group. Mean time frame between first priming and delivery has been measured in our department in 2018 to 31.8 hours (standard deviation 27.6 hours).

• Study Type: Interventional
• Enrollment (Actual): 268
• Phase: Phase 2

Contacts and Locations

Study Locations

• Martinique
  • Fort-de-France, Martinique, 97261
    • University Hospital of Martinique

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients above 18 years
• Gestational age ≥ 37 weeks
• With indicated induction of labor and initial Bishop score under 6
• Without any contraindication to vaginal delivery
• Who consent to participate to the clinical research
• With French Medical Public Insurance

Exclusion Criteria:

• Multiple pregnancy
• Previous uterine scar (for myomas or cesarean section)
• Fetus not in cephalic presentation
• Allergy to prostaglandins
• Who not consent to participate to the study

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
Active Comparator: Classical administration; One prostaglandin vaginal gel every 24 hours	Drug: Dinoprostone vaginal gel; Prostaglandin gel 0.5, 1 or 2 mg; Other Names: cervical priming with prostaglandin gel
Experimental: Experimental administration; One prostaglandin vaginal gel every 12 hours	Drug: Dinoprostone vaginal gel; Prostaglandin gel 0.5, 1 or 2 mg; Other Names: cervical priming with prostaglandin gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time between gel administration and delivery	Time between first gel administration for cervical priming and delivery	At inclusion (Day 0)
Time between gel administration and delivery	Change between cervical priming and delivery	At 12 hours or 24 hours (after each gel administration)
Time between gel administration and delivery	Time between first gel administration for cervical priming and delivery	Time 0 after the childbirth
Time between gel administration and delivery	Time between first gel administration for cervical priming and delivery	Until 5 days postpartum (during in-hospital postpartum period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal satisfaction	maternal satisfaction measured by survey self-administered during postpartum hospital stay	Until 5 days postpartum
Cesarean section rate		During labor
Hypertonia / hypercinesia rate	Hypertonia (rise of uterus tone more than 10 minutes)/hypercinesia (more than 5 uterine contractions per 10 minutes) rate during priming and induction	During priming and induction
Oxytocin dose during labor	Induction or augmentation of Oxytocin doses	During labor
Length of active first phase of labor	Induction or augmentation of active first phase of labor	During labor
Maternal morbidity	Fever during labor, perineal laceration superior to 2nd degree, postpartum hemorrhage, endometritis	During labor
Neonatal immediate morbidity	Assess if Apgar score is less than 7	5 minutes after childbirth
Neonatal immediate morbidity	Assess of arterial cord pH level	5 minutes after childbirth
Neonatal immediate morbidity	Assess of arterial cord lactate level	5 minutes after childbirth
Neonatal immediate morbidity	Concentration of arterial cord lactates level (in Mmol/L)	5 minutes after childbirth
Neonatal immediate morbidity	Occurence or not of resuscitation maneuvers in delivery room	5 minutes after childbirth
Neonatal immediate morbidity	Occurence or no transfer of the child to neonatal intensive care unit	5 minutes after childbirth

Collaborators and Investigators

• Sponsor: University Hospital Center of Martinique
• Investigators: Principal Investigator: Jean-Luc VOLUMENIE, University Hospital of Martinique

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2019
• Primary Completion (Actual): January 27, 2021
• Study Completion (Actual): January 27, 2021

Study Registration Dates

• First Submitted: April 7, 2020
• First Submitted That Met QC Criteria: May 29, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: July 18, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Term; Labor; Induction; Rhythm; Prostaglandins
• Additional Relevant MeSH Terms: Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Obstetric Labor Complications; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Dinoprostone
• Other Study ID Numbers: 19_RIPH2_10

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No