Effect of Tafoxiparin on Cervical Ripening and Induction of Labor in Term Pregnant Women With an Unripe Cervix

Labor Onset and Length Abnormalities Clinical Trial

Official title:

Randomized, Placebo-Controlled, Proof of Concept Study to Evaluate the Efficacy on Cervical Ripening, Safety, Tolerability and Dose Response of SC Administered Tafoxiparin in Term Pregnant, Nulliparous Women With an Unripe Cervix Undergoing Labor Induction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04000438
• Other study ID #: PPL17
• Secondary ID: 2019-000620-17
• Status: Completed
• Phase: Phase 2
• Start date: June 21, 2019
• Est. completion date: March 30, 2023

Study information

• Verified date: March 2023
• Source: Dilafor AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is designed as a randomized, Double-Blind, Placebo-Controlled, Parallel-Group Proof of Concept Study (section A) with a conditional dose finding follow up (Section B) to Evaluate the Efficacy on Cervical ripening, Safety, Tolerability and dose response of Subcutaneously Administered Tafoxiparin in Term Pregnant, Nulliparous Women with an unripe cervix undergoing Labor Induction. If the efficacy and safety profiles of Section A are conclusive in favor of tafoxiparin, the study will continue by adding two additional tafoxiparin dose groups in Section B.

Description:

Primary objective:

To assess the efficacy of tafoxiparin on cervical ripening.

Secondary objective:

To assess the maternal and neonatal safety, tolerability and dose response of tafoxiparin as a supplement therapy in term pregnant, nulliparous women with an unripe cervix undergoing labor induction

Methodology:

Term pregnant, nulliparous women with unripe cervix and planned for labor induction are potential study patients unless enrolled in another study. Subjects may be preinformed about the stuyd through the use of advertisement or information at the physician/midwife visits during pregnancy and at the hospital admission.

The whole study includes the following steps:

Screening and Baseline including informed consent and randomization Study treatment and Induction of Labor Labor Discharge

Recruitment information / eligibility

• Status: Completed
• Enrollment: 347
• Est. completion date: March 30, 2023
• Est. primary completion date: February 14, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Pregnant women of =18 and = 64 years of age

• Nulliparous

• Unripe cervix with = 4points according to Bishop/Westin score (0-10 points scale)

• Planned for labor induction after 4-7 days of IMP treatment

• Examples of diagnosis as a basis for induction:

• Post term pregnancy (40-41 weeks of gestation)

• Gestational diabetes

• Diabetes type 1 - well controlled

• Pre-eclampsia (BP diastolic <100, systolic <140)

• Hypertension - well controlled

• Hepatosis (without clinically significantly elevated serum bile acids)

• Maternal age = 40 years

• Humanitarian-psycho social reasons

• Oligohydramnios

• Gestational age > 37 weeks confirmed by ultrasound before 21 weeks of gestation

• Singleton pregnancy

• Subject is, as per the discretion of the Investigator, able to comply with the requirements of the protocol including an ability to be present at all required controls

• Subject can understand and sign an informed form

• Provision of written informed consent

Exclusion Criteria:

• Subjects who are unable to understand the written and verbal instructions in local language

• Breech presentation and other abnormal fetal presentations

• Previous uterine scar

• Spontaneous rupture of membranes at inclusion

• Pathologic CTG at inclusion

• Fetal estimated weight > 2SD of normal fetal estimated weight earlier diagnosed by ultrasound and documented in patient record

• Mother's BMI > 35 at early pregnancy

• Known IUGR defined as = 2SD of normal

• Presence of eclampsia

• Severe Pre-eclampsia

• HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)

• Clinically significant vaginal bleeding in need of hospitalization in the third trimester

• Placenta previa

• Previously known coagulation disorders (Leiden, heterozygote - OK)

• Current use of any drugs that interfere with hemostasis (including heparin /LMWH, direct oral anti-coagulant medication, non-steroidal anti-inflammatory drugs (NSAID) compounds and vitamin K antagonists.)

• Current use of acetylsalicylic acid (ASA) compounds or use within the week preceding inclusion

• Diagnosed with HIV or Acute hepatitis

• Known history of allergy to standard heparin and/or LMWH heparin

• History of heparin-induced thrombocytopenia

• Current drug or alcohol abuse which in the opinion of the Investigator should preclude participation in the study.

• Current participation in other interventional medicinal treatment studies

• Subject has a fear of needles which is believed by the Investigator to affect study medication compliance

Related Conditions & MeSH terms

• Congenital Abnormalities
• Labor Onset and Length Abnormalities

Intervention

Drug:
• DF01
The subject receives sc injections of tafoxiparin solution once daily for up to 7 days until labor induction or spontaneous onset of labor. Induction is done according to clinical practice; 1st balloon, 2nd PGE1
• PL1
The subject receives sc injections once daily of placebo solution for up to 7 days until labor induction or spontaneous onset of labor. Induction is done according to clinical practice; 1st balloon, 2nd PGE1

Locations

Country	Name	City	State
Finland	Naistenklinikka (HUS)	Helsinki
Finland	Tampere University Hospital	Tampere
Sweden	Kvinnokliniken Universitetssjukhuset Linköping	Linköping
Sweden	Lund University Hospital	Lund
Sweden	Kvinnokliniken Skaraborgs Sjukhus	Skövde
Sweden	Kvinnokliniken Södersjukhuset	Stockholm
Sweden	Förlossningsavdelningen Akademiska Universitetssjukhuset	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Dilafor AB

Countries where clinical trial is conducted

Finland,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of cervical ripening	Cervical ripening rate during up to the first seven days of treatment, measured by Bishop Score	From start of study drug administration to cervical ripening (up to 7 days)
Secondary	Time to start of treatment in relation to cervical ripening = 2 points	Time from start of treatment to increase in Bishop score of = 2 points or spontaneous onset of labor, whichever comes first	From start of study drug administration to cervical ripening (up to 7 days)
Secondary	Time to start of treatment in relation to cervical ripening = 3 points	Time from start of treatment to increase in Bishop score of = 3 points or spontaneous onset of labor, whichever comes first	From start of study drug administration to cervical ripening (up to 7 days)
Secondary	Time to start of treatment in relation to cervical ripening = 4 points	Time from start of treatment to increase in Bishop score of = 4 points or spontaneous onset of labor, whichever comes first	From start of study drug administration to cervical ripening (up to 7 days)
Secondary	Time to partus from labor onset	Time from onset of labor to partus. Onset of labor is defined as last record of 4 cm cervical dilatation visualized in the partogram and progress of labor or last record of 4 cm of cervical dilatation in combination with amniotomy and intravenous administration oxytocin	Interval from 4 cm of cervical dilatation until delivery (hours up to 36 hours)
Secondary	Time of labor = 6 hours	Proportion of women with established labor = 6 hours	Interval from 4 cm of cervical dilatation until delivery (hours up to 36 hours)
Secondary	Time of labor = 12 hours	Proportion of women with established labor = 12 hours	Interval from 4 cm of cervical dilatation until delivery (hours up to 36 hours)
Secondary	Dosages of study drug	Total dosages of study drug (IMP)	From start of study drug administration to cervical ripening (up to 7 days)
Secondary	Secondary Safety and tolerability endpoint - adverse event and serious adverse event	Safety and tolerability will be evaluated through rate and frequency of adverse events and serious adverse events. The AE and SAE will be coded using MedDRA version 19.1.	Through study completion (up to 3 days after delivery)
Secondary	Secondary Safety and tolerability endpoint- caesarean sections	Proportion of patients undergoing caesarean sections (CS)	From start of study drug administration until delivery (up to 7 days)
Secondary	Secondary Safety and tolerability endpoint- indications for caesarean sections	Indications for CS	From start of study drug administration until delivery (up to 7 days)
Secondary	Secondary Safety and tolerability endpoint -instrumental deliveries	Proportion of patients undergoing instrumental deliveries (vacuum extraction (VE)/forceps delivery)	From start of study drug administration until delivery (up to 7 days)
Secondary	Secondary Safety and tolerability endpoint- VE and forceps deliveries	Indications for VE and forceps deliveries	From start of study drug administration until delivery (up to 7 days)
Secondary	Secondary Safety and tolerability endpoint- fetal outcome- Birth weight	Fetal outcome measured as Birth weight (kg)	From start of study drug administration until delivery ( up to 7 days)
Secondary	Secondary Safety and tolerability endpoint- fetal outcome -Apgar score	Fetal outcome measured as Apgar score (1-10 points). A score > 7 is good health.	From start of study drug administration until delivery ( up to 7 days)
Secondary	Secondary Safety and tolerability endpoint- fetal outcome - Acidosis and/or Base excess	Fetal outcome measured as number of neonatal with Acidosis (pH<7.10) and/or Base Excess < -12 mmol/L arterial or venous in umbilical cord blood	From start of study drug administration until delivery ( up to 7 days)
Secondary	Secondary Safety and tolerability endpoint - NICU	Indication for referral to neonatal intensive care unit (NICU)	From start of study drug administration until delivery (days)
Secondary	Secondary Safety and tolerability endpoint - NICU	Proportion of infants staying in the NICU for > 48 hours	From start of study drug administration until delivery (up to 7 days)
Secondary	Secondary Safety and tolerability endpoint - tocolytica	Uterine hyper stimulation in demand of tocolytic treatment	From start of study drug administration until delivery (up to 7 days)
Secondary	Secondary Safety and tolerability endpoint - PPH	Proportion of patients with Postpartum Hemorrhage (PPH) > 2000 ml	From start of study drug administration until delivery (up to 7 days)