A Randomised Trial Investigating the Efficacy and Safety of a Vaginal Insert in Pregnant Women at Term

Cervical Ripening Clinical Trial

Official title:

A Multicentre, Randomised, Double-blind, Placebo-controlled Phase III Trial Investigating the Efficacy and Safety of FE 999901 Vaginal Insert in Pregnant Women at Term (41 Weeks of Gestation) Requiring Cervical Ripening

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03067727
• Other study ID #: 000262
• Status: Completed
• Phase: Phase 3
• Start date: April 3, 2017
• Est. completion date: August 30, 2018

Study information

• Verified date: September 2018
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To demonstrate the efficacy of dinoprostone vaginal insert (DVI) for cervical ripening success (either bishop score (BS) ≥7 or vaginal delivery) within 12 hours of vaginal insert administration

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: August 30, 2018
• Est. primary completion date: August 30, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Pregnant women at term (= 41 weeks 0 day and = 41 weeks 6 days 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 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 (= 1.5 SD of mean 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 baseline visit

• Ruptured membranes

• 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 (eg., 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 investigator would impair participation in the trial

Related Conditions & MeSH terms

• Cervical Ripening

Intervention

Drug:
• Dinoprostone
The DVI contains 10 mg Dinoprostone
• Placebo
The placebo product is identical with the active product except that it does not contain Dinoprostone.

Locations

Country	Name	City	State
Japan	Asahi General Hospital	Chiba
Japan	Hamamatsu University Hospital	Hamamatsu	Shizuoka
Japan	Seirei Hamamatsu General Hospital	Hamamatsu	Shizuoka
Japan	University of Tsukuba Hospital	Ibaraki
Japan	Itabashi Chuo Medical Center	Itabashi	Tokyo
Japan	Osaka Medical Center and Research Institute for Maternal and Child Health	Izumi	Osaka
Japan	Hori Hospital	Kanagawa
Japan	Aizenbashi Hospital	Osaka
Japan	Osaka University Hospital	Osaka
Japan	Rinku General Medical Center	Osaka
Japan	Jichi Medical University Hospital	Shimotsuke	Tochigi
Japan	Juntendo University Hospital	Tokyo
Japan	Keio University Hospital	Tokyo
Japan	Seibo Hospital	Tokyo
Japan	Showa University Hospital	Tokyo
Japan	St.Luke's International Hospital	Tokyo
Japan	The University of Tokyo Hospital	Tokyo
Japan	Tokyo Metropolitan Bokutoh Hospital	Tokyo
Japan	Tokyo Metropolitan Tama Medical Center	Tokyo
Japan	Keiyu Hospital	Yokohama

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Country where clinical trial is conducted

Japan, 

References & Publications (1)

Itoh H, Ishii K, Shigeta N, Itakura A, Hamada H, Nagamatsu T, Ishida T, Bungyoku Y, Falahati A, Tomisaka M, Kitamura M. Efficacy and safety of controlled-release dinoprostone vaginal delivery system (PROPESS) in Japanese pregnant women requiring cervical — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of women with cervical ripening success	Defined as either Bishop Score (BS) =7 or a vaginal delivery	Within 12 hours of vaginal insert administration
Secondary	Proportion of nulliparous and multiparous subjects with cervical ripening success	Collected labour data and delivery data	Within 12 hours of Investigational Medicinal Product (IMP) administration
Secondary	Proportion of subjects delivering vaginally	Collected labour and delivery data	Within 12 hours of IMP administration
Secondary	Proportion of subjects delivering vaginally	Collected labour data and delivery data	Within the first admission to hospital
Secondary	Proportion of subjects with a BS increase =3 points from baseline	Measured by BS assessments	Within 12 hours of IMP administration
Secondary	Proportion of subjects who have a caesarean delivery within the first admission to hospital	Data collected during the first admission to hospital	At time of delivery
Secondary	Proportion of subjects who receive pre-delivery oxytocic drugs and dose of pre-delivery oxytocic drugs	Collected pre-delivery data	From the IMP removal to delivery
Secondary	Proportion of subjects who undergo mechanical cervical ripening	Collected labour data	At least 60 minutes after the removal of the IMP
Secondary	Duration of mechanical cervical ripening for subjects who undergo mechanical Cervical ripening	Measured as start date and time of first mechanical ripening and the end date and time of last mechanical ripening	Time from at least 60 minutes after the removal of the IMP until end of any mechanical ripening
Secondary	Proportion of subjects with BS =7	Among those having onset of labour while IMP is in-situ	At onset of labour
Secondary	Time from IMP administration to onset of active labour	Within the first admission to hospital	Interval from IMP administration to onset of active labour
Secondary	Time from IMP administration to vaginal delivery, caesarean delivery and any delivery	Within the first admission to hospital	Interval from IMP administration to delivery
Secondary	Type, frequency and intensity of intrapartum adverse events (AEs), postpartum AEs and neonatal AEs	Assessed up to time when the subjects are discharged from the hospital	From obtaining the informed consent through end of trial (expected average of up to 1 week)
Secondary	Type, frequency and intensity of intrapartum AEs	Assessed up to time when the deliveries occur	From onset of labour to the removal of the IMP
Secondary	Change in maternal parameters of vital signs (blood pressure, heart rate and body temperature)	Assessed up to time when the subjects are discharged from the hospital	From baseline through end of trial (expected average of up to 1 week)
Secondary	Change in maternal parameters of haematology, clinical chemistry and urinalysis	Assessed up to time when the subjects are discharged from the hospital	From baseline to end of trial (expected average of up to 1 week)
Secondary	Proportion of neonates with Apgar Score <7	Measured as Apgar Score assessments	5 minutes post-birth
Secondary	pH in umbilical artery blood samples	pH evaluation	At birth
Secondary	Rate of admission to neonatal intensive care unit (NICU) for at least 24 hours	Admission/discharge data from NICU	After delivery