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

NCT ID: NCT04000438

Last Updated: 2025-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 365 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-21
• Study Completion Date: 2023-03-30

Brief 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.

Detailed 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 study 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

Conditions

Labor Onset and Length Abnormalities

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Experimental DF01 high dose

The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.

Group Type: EXPERIMENTAL

DF01

Intervention Type: DRUG

DF01: The subject receives sc injections of tafoxiparin solution once daily for up to 7 days until spontaneous onset of labor or ripe cervix (Amniotomy/oxytocin without restriction).If not enough ripening cervical ripening according to clinical practice with intracervical ballon/prostaglandins

Experimental: DF01 medium dose

The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.

Group Type: EXPERIMENTAL

DF01

Intervention Type: DRUG

DF01: The subject receives sc injections of tafoxiparin solution once daily for up to 7 days until spontaneous onset of labor or ripe cervix (Amniotomy/oxytocin without restriction).If not enough ripening cervical ripening according to clinical practice with intracervical ballon/prostaglandins

Experimental: DF01 low dose

The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.

Group Type: EXPERIMENTAL

DF01

Intervention Type: DRUG

DF01: The subject receives sc injections of tafoxiparin solution once daily for up to 7 days until spontaneous onset of labor or ripe cervix (Amniotomy/oxytocin without restriction).If not enough ripening cervical ripening according to clinical practice with intracervical ballon/prostaglandins

Placebo comparator: PL1

The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.

Group Type: PLACEBO_COMPARATOR

PL1

Intervention Type: DRUG

DF01: The subject receives sc injections of placebo solution once daily for up to 7 days until spontaneous onset of labor or ripe cervix (Amniotomy/oxytocin without restriction).If not enough ripening cervical ripening according to clinical practice with intracervical ballon/prostaglandins

Interventions

DF01

DF01: The subject receives sc injections of tafoxiparin solution once daily for up to 7 days until spontaneous onset of labor or ripe cervix (Amniotomy/oxytocin without restriction).If not enough ripening cervical ripening according to clinical practice with intracervical ballon/prostaglandins

Intervention Type: DRUG

PL1

DF01: The subject receives sc injections of placebo solution once daily for up to 7 days until spontaneous onset of labor or ripe cervix (Amniotomy/oxytocin without restriction).If not enough ripening cervical ripening according to clinical practice with intracervical ballon/prostaglandins

Intervention Type: DRUG

Other Intervention Names

tafoxiparin; Placebo

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Dilafor AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gunvor Ekman-Ordeberg, MD, PhD, Study Chair, CMO

Role: STUDY_CHAIR

CMO

Locations

Naistenklinikka (HUS)

Helsinki, , Finland

Tampere University Hospital

Tampere, , Finland

Kvinnokliniken Universitetssjukhuset Linköping

Linköping, , Sweden

Lund University Hospital

Lund, , Sweden

Kvinnokliniken Skaraborgs Sjukhus

Skövde, , Sweden

Kvinnokliniken Södersjukhuset

Stockholm, , Sweden

Förlossningsavdelningen Akademiska Universitetssjukhuset

Uppsala, , Sweden

Countries

Finland; Sweden

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2019-000620-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PPL17

Identifier Type: -

Identifier Source: org_study_id