Clinical trial NCT03067597: An Open-label Trial Investigating the Efficacy and Safety of a Vaginal Insert in Pregnant Women at Term
Official title: A Multicentre, Open-label Phase III Trial Investigating the Efficacy and Safety of FE 999901 Vaginal Insert in Pregnant Women at Term (≥37 Weeks and <41 Weeks of Gestation) Requiring Cervical Ripening
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Ripening
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-03-01
Enrollment: 68
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To demonstrate the efficacy of controlled-release dinoprostone vaginal insert (DVI) for cervical ripening success (either Bishop Score (BS) ≥7 or vaginal delivery) within 12 hours of vaginal insert administration.


Eligibility criteria: Inclusion Criteria:

* Pregnant women at term (≥37 weeks 0 day and \< 41 weeks 0 day of gestation) at the Baseline visit
* Candidate for pharmacologic induction of labour
* Singleton pregnancy with live infant in vertex presentation
* Baseline BS ≤ 4 at the Baseline visit
* Parity ≤ 3 (parity is defined as one or more births live or stillbirths after 22 weeks 0 day gestation)
* Written informed consent

Exclusion Criteria:

* Women in active labour
* Presence of uterine or cervical scar including scar from previous caesarean section, and previous cone biopsy of the cervix and loop electrosurgical excision procedure (LEEP)
* Uterine abnormality e.g. bicornuate uterus
* Administration of oxytocin, any cervical ripening or labour inducing agents (including mechanical methods) or a tocolytic drug within 7 days prior to IMP administration. Magnesium sulfate is permitted if prescribed as treatment for preeclampsia or pregnancy induced hypertension
* Presence of the following conditions/symptoms:

Systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 110 mmHg. Platelets \< 100,000/µL. Increased liver function tests (2x upper limits of normal range). Severe, persistent right upper quadrant/epigastric pain. Progressive renal insufficiency: Creatinine \> 1.1 mg/dL, Doubling of creatinine in the absence of other renal disease. Pulmonary edema. New onset cerebral or visual disturbances.

* Suspected or confirmed cephalopelvic disproportion and/or fetal malpresentation
* Diagnosed congenital abnormalities, not including polydactyly
* Suspected or confirmed intrauterine growth retardation (≤ mean 1.5 SD of normal estimated fetal weight for dates)
* Any evidence of fetal compromise at Baseline visit (e.g., non-reassuring fetal heart rate pattern, meconium staining, history of non-reassuring fetal status or abnormal umbilical artery Doppler wave form)
* Intake of medication with aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) at V2
* Ruptured membranes ≥ 48 hours prior to IMP administration
* Suspected clinical chorioamnionitis
* Current pelvic inflammatory disease, unless adequate prior treatment has been instituted
* Fever (axillary temperature ≥ 38.0°C) at the Baseline visit
* Any condition in which vaginal delivery is contraindicated (e.g., placenta previa or any unexplained vaginal bleeding at any time after 24 weeks 0 day during this pregnancy)
* Known or suspected allergy to, dinoprostone, other prostaglandins or any constituent of IMP
* Any condition urgently requiring delivery
* History of asthma or glaucoma
* Unable to comply with the protocol
* Any other medical condition which in the judgement of the investigators would impair participation in the trial

Primary outcomes:
measure: The proportion of women with cervical ripening success
timeFrame: Within 12 hours of vaginal insert administration
Secondary outcomes:
measure: Proportion of nulliparous and multiparous subjects with cervical ripening success
timeFrame: Within 12 hours of Investigational Medicinal Product (IMP) administration
measure: Proportion of subjects delivering vaginally
timeFrame: Within 12 hours of IMP administration
measure: Proportion of subjects delivering vaginally
timeFrame: Within the first admission to hospital
measure: Proportion of subjects with a BS increase ≥3 points from baseline
timeFrame: Within 12 hours of IMP administration
measure: Proportion of subjects who have a caesarean delivery within the first admission to hospital
timeFrame: At time of delivery
measure: Proportion of subjects who receive pre-delivery oxytocic drugs and dose of pre-delivery oxytocic drugs
timeFrame: From the IMP removal to delivery
measure: Proportion of subjects who undergo mechanical cervical ripening
timeFrame: At least 60 minutes after the removal of the IMP
measure: Duration of mechanical cervical ripening for subjects who undergo mechanical cervical ripening
timeFrame: Time from at least 60 minutes after the removal of the IMP until end of any mechanical ripening
measure: Proportion of subjects with BS ≥7
timeFrame: At onset of labour
measure: Time from IMP administration to onset of active labour
timeFrame: Interval from IMP administration to onset of active labour
measure: Time from IMP administration to vaginal delivery, caesarean delivery and any delivery
timeFrame: Interval from IMP administration to delivery
measure: Type, frequency and intensity of intrapartum adverse events (AEs), postpartum AEs and neonatal AEs
timeFrame: From obtaining the informed consent through end of trial (expected average of up to 1 week)
measure: Type, frequency and intensity of intrapartum AEs
timeFrame: From obtaining the informed consent to the removal of the IMP
measure: Change in maternal parameters of vital signs (blood pressure, heart rate and body temperature)
timeFrame: From baseline through end of trial (expected average of up to 1 week)
measure: Change in maternal parameters of haematology, clinical chemistry and urinalysis
timeFrame: From baseline to end of trial (expected average of up to 1 week)
measure: Proportion of neonates with Apgar Score <7
timeFrame: 5 minutes post-birth
measure: pH in umbilical artery blood samples
timeFrame: At birth
measure: Rate of admission to neonatal intensive care unit (NICU) for at least 24 hours
timeFrame: After delivery
Other outcomes:
Locations:
city: Maebashi
country: Japan
facility: Yokota Maternity Hospital
state: Gunma
city: Sagamihara
country: Japan
facility: Kitasato University Hospital
state: Kanagawa
city: Izumi
country: Japan
facility: Osaka Medical Center and Research Institute for Maternal and Child Health
state: Osaka
city: Hamamatsu
country: Japan
facility: Hamamatsu University Hospital
state: Shizuoka
city: Hamamatsu
country: Japan
facility: Seirei Hamamatsu General Hospital
state: Shizuoka
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Itabashi
country: Japan
facility: Itabashi Chuo Medical Center
state: Tokyo
city: Ibaraki
country: Japan
facility: University of Tsukuba Hospital
state: Tsukuba
city: Kanagawa
country: Japan
facility: Hori Hospital
city: Osaka
country: Japan
facility: Rinku General Medical Center
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Keio University Hospital
city: Tokyo
country: Japan
facility: The University of Tokyo Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Bokutoh Hospital
Study officials:
affiliation: Ferring Pharmaceuticals
name: Clinical Development Support
role: STUDY_DIRECTOR
References: