Back to resultsEffect of Tafoxiparin on Cervical Ripening and Induction of Labor in Term Pregnant Women With an Unripe Cervix
Primary Purpose
Labor Onset and Length Abnormalities
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
DF01
PL1
Sponsored by
About this trial
This is an interventional treatment trial for Labor Onset and Length Abnormalities focused on measuring labor induction, cervical ripening
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
Sites / Locations
- Naistenklinikka (HUS)
- Tampere University Hospital
- Kvinnokliniken Universitetssjukhuset Linköping
- Lund University Hospital
- Kvinnokliniken Skaraborgs Sjukhus
- Kvinnokliniken Södersjukhuset
- Förlossningsavdelningen Akademiska Universitetssjukhuset
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Experimental DF01 high dose
Experimental: DF01 medium dose
Experimental: DF01 low dose
Placebo comparator: PL1
Arm Description
The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
Outcomes
Primary Outcome Measures
Rate of cervical ripening
Cervical ripening rate during up to the first seven days of treatment, measured by Bishop Score
Secondary Outcome Measures
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
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
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
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
Time of labor ≤ 6 hours
Proportion of women with established labor ≤ 6 hours
Time of labor ≥ 12 hours
Proportion of women with established labor ≥ 12 hours
Dosages of study drug
Total dosages of study drug (IMP)
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.
Secondary Safety and tolerability endpoint- caesarean sections
Proportion of patients undergoing caesarean sections (CS)
Secondary Safety and tolerability endpoint- indications for caesarean sections
Indications for CS
Secondary Safety and tolerability endpoint -instrumental deliveries
Proportion of patients undergoing instrumental deliveries (vacuum extraction (VE)/forceps delivery)
Secondary Safety and tolerability endpoint- VE and forceps deliveries
Indications for VE and forceps deliveries
Secondary Safety and tolerability endpoint- fetal outcome- Birth weight
Fetal outcome measured as Birth weight (kg)
Secondary Safety and tolerability endpoint- fetal outcome -Apgar score
Fetal outcome measured as Apgar score (1-10 points). A score > 7 is good health.
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
Secondary Safety and tolerability endpoint - NICU
Indication for referral to neonatal intensive care unit (NICU)
Secondary Safety and tolerability endpoint - NICU
Proportion of infants staying in the NICU for > 48 hours
Secondary Safety and tolerability endpoint - tocolytica
Uterine hyper stimulation in demand of tocolytic treatment
Secondary Safety and tolerability endpoint - PPH
Proportion of patients with Postpartum Hemorrhage (PPH) > 2000 ml
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04000438
Brief Title
Effect of Tafoxiparin on Cervical Ripening and Induction of Labor in Term Pregnant Women With an Unripe Cervix
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
June 21, 2019 (Actual)
Primary Completion Date
February 14, 2023 (Actual)
Study Completion Date
March 30, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dilafor AB
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Labor Onset and Length Abnormalities
Keywords
labor induction, cervical ripening
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
347 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental DF01 high dose
Arm Type
Experimental
Arm Description
The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
Arm Title
Experimental: DF01 medium dose
Arm Type
Experimental
Arm Description
The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
Arm Title
Experimental: DF01 low dose
Arm Type
Experimental
Arm Description
The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
Arm Title
Placebo comparator: PL1
Arm Type
Placebo Comparator
Arm Description
The subject receives sc injections once daily for up to 7 days until labor induction or spontaneous onset of labor.
Intervention Type
Drug
Intervention Name(s)
DF01
Other Intervention Name(s)
tafoxiparin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
PL1
Other Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Rate of cervical ripening
Description
Cervical ripening rate during up to the first seven days of treatment, measured by Bishop Score
Time Frame
From start of study drug administration to cervical ripening (up to 7 days)
Secondary Outcome Measure Information:
Title
Time to start of treatment in relation to cervical ripening ≥ 2 points
Description
Time from start of treatment to increase in Bishop score of ≥ 2 points or spontaneous onset of labor, whichever comes first
Time Frame
From start of study drug administration to cervical ripening (up to 7 days)
Title
Time to start of treatment in relation to cervical ripening ≥ 3 points
Description
Time from start of treatment to increase in Bishop score of ≥ 3 points or spontaneous onset of labor, whichever comes first
Time Frame
From start of study drug administration to cervical ripening (up to 7 days)
Title
Time to start of treatment in relation to cervical ripening ≥ 4 points
Description
Time from start of treatment to increase in Bishop score of ≥ 4 points or spontaneous onset of labor, whichever comes first
Time Frame
From start of study drug administration to cervical ripening (up to 7 days)
Title
Time to partus from labor onset
Description
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
Time Frame
Interval from 4 cm of cervical dilatation until delivery (hours up to 36 hours)
Title
Time of labor ≤ 6 hours
Description
Proportion of women with established labor ≤ 6 hours
Time Frame
Interval from 4 cm of cervical dilatation until delivery (hours up to 36 hours)
Title
Time of labor ≥ 12 hours
Description
Proportion of women with established labor ≥ 12 hours
Time Frame
Interval from 4 cm of cervical dilatation until delivery (hours up to 36 hours)
Title
Dosages of study drug
Description
Total dosages of study drug (IMP)
Time Frame
From start of study drug administration to cervical ripening (up to 7 days)
Title
Secondary Safety and tolerability endpoint - adverse event and serious adverse event
Description
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.
Time Frame
Through study completion (up to 3 days after delivery)
Title
Secondary Safety and tolerability endpoint- caesarean sections
Description
Proportion of patients undergoing caesarean sections (CS)
Time Frame
From start of study drug administration until delivery (up to 7 days)
Title
Secondary Safety and tolerability endpoint- indications for caesarean sections
Description
Indications for CS
Time Frame
From start of study drug administration until delivery (up to 7 days)
Title
Secondary Safety and tolerability endpoint -instrumental deliveries
Description
Proportion of patients undergoing instrumental deliveries (vacuum extraction (VE)/forceps delivery)
Time Frame
From start of study drug administration until delivery (up to 7 days)
Title
Secondary Safety and tolerability endpoint- VE and forceps deliveries
Description
Indications for VE and forceps deliveries
Time Frame
From start of study drug administration until delivery (up to 7 days)
Title
Secondary Safety and tolerability endpoint- fetal outcome- Birth weight
Description
Fetal outcome measured as Birth weight (kg)
Time Frame
From start of study drug administration until delivery ( up to 7 days)
Title
Secondary Safety and tolerability endpoint- fetal outcome -Apgar score
Description
Fetal outcome measured as Apgar score (1-10 points). A score > 7 is good health.
Time Frame
From start of study drug administration until delivery ( up to 7 days)
Title
Secondary Safety and tolerability endpoint- fetal outcome - Acidosis and/or Base excess
Description
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
Time Frame
From start of study drug administration until delivery ( up to 7 days)
Title
Secondary Safety and tolerability endpoint - NICU
Description
Indication for referral to neonatal intensive care unit (NICU)
Time Frame
From start of study drug administration until delivery (days)
Title
Secondary Safety and tolerability endpoint - NICU
Description
Proportion of infants staying in the NICU for > 48 hours
Time Frame
From start of study drug administration until delivery (up to 7 days)
Title
Secondary Safety and tolerability endpoint - tocolytica
Description
Uterine hyper stimulation in demand of tocolytic treatment
Time Frame
From start of study drug administration until delivery (up to 7 days)
Title
Secondary Safety and tolerability endpoint - PPH
Description
Proportion of patients with Postpartum Hemorrhage (PPH) > 2000 ml
Time Frame
From start of study drug administration until delivery (up to 7 days)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gunvor Ekman-Ordeberg, M,mPhD
Organizational Affiliation
CMO
Official's Role
Study Chair
Facility Information:
Facility Name
Naistenklinikka (HUS)
City
Helsinki
ZIP/Postal Code
00029
Country
Finland
Facility Name
Tampere University Hospital
City
Tampere
ZIP/Postal Code
33521
Country
Finland
Facility Name
Kvinnokliniken Universitetssjukhuset Linköping
City
Linköping
ZIP/Postal Code
581 85
Country
Sweden
Facility Name
Lund University Hospital
City
Lund
Country
Sweden
Facility Name
Kvinnokliniken Skaraborgs Sjukhus
City
Skövde
ZIP/Postal Code
54185
Country
Sweden
Facility Name
Kvinnokliniken Södersjukhuset
City
Stockholm
ZIP/Postal Code
11883
Country
Sweden
Facility Name
Förlossningsavdelningen Akademiska Universitetssjukhuset
City
Uppsala
ZIP/Postal Code
751 85
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Effect of Tafoxiparin on Cervical Ripening and Induction of Labor in Term Pregnant Women With an Unripe Cervix
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