E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Induction of labor in pregnant women with unripe cervix |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055563 |
E.1.2 | Term | Labor induction |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the Efficacy of tafoxiparin on cervical ripening |
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E.2.2 | Secondary objectives of the trial |
To assess the maternal and neonatal safety, tolerability and dose response of tafoxiparin as an adjuvant therapy in term pregnant, nulliparous women with an unripe cervix |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
i) Pregnant women of ≥18 and ≤ 64 years of age ii) Nulliparous iii) Unripe cervix with ≤ 4points according to Bishop/Westin score (0-10 points scale) iv) 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) Hepatosis (without clinically significantly elevated serum bile acids) Maternal age 40 years Humanitarian-psycho social reasons Oligohydramnios v) Gestational age > 37 weeks confirmed by ultrasound before 21 weeks of gestation vi) Singleton pregnancy vii) 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 viii) Subject can understand and sign an informed form ix) Provision of written informed consent
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E.4 | Principal exclusion criteria |
i) Subjects who are unable to understand the written and verbal instructions in local language ii) Breech presentation and other abnormal fetal presentations iii) Previous uterine scar iv) Spontaneous rupture of membranes at inclusion v) Pathologic CTG at inclusion vi) Fetal estimated weight > 2SD of normal fetal estimated weight earlier diagnosed by ultrasound and documented in patient record vii) Mother’s BMI > 35 at early pregnancy viii) Known IUGR defined as ≤ 2SD of normal ix) Presence of eclampsia x) Severe Pre-eclampsia xi) HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) xii) Clinically significant vaginal bleeding in need of hospitalization in the third trimester xiii) Placenta previa xiv) Previously known coagulation disorders (Leiden, heterozygote - OK) xv) Treatment with a heparin/LMWH product during the previous six months xvi) Current use of any drugs that interfere with hemostasis such as oral anti-coagulant medication, non-steroidal anti-inflammatory drugs (NSAID) compounds and vitamin K antagonists. xvii) Current use of acetylsalicylic acid (ASA) compounds or use within the week preceding inclusion xviii) Diagnosed with HIV or Acute hepatitis xix) Known history of allergy to standard heparin and/or LMWH heparin xx) History of heparin-induced thrombocytopenia xxi) Current drug or alcohol abuse which in the opinion of the Investigator should preclude participation in the study. xxii) Current participation in other interventional medicinal treatment studies xxiii) Subject has a fear of needles which is believed by the Investigator to affect study medication compliance xxiv) Any relevant condition, laboratory value or concomitant medication which, in the opinion of the investigator, makes the subject unsuitable for entry into the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Cervical ripening rate during up to the first seven days of treatment, measured by Bishop score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During up to the first seven days of treatment |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy endpoints include: i) Time from start of treatment to increase in Bishop score of ≥ 2 points or spontaneous onset of labor, whichever comes first ii) Time from start of treatment to increase in Bishop score of ≥ 3 points or spontaneous onset of labor, whichever comes first iii) Time from start of treatment to increase in Bishop score of ≥ 4 points or spontaneous onset of labor, whichever comes first iv) Cervical ripening as measured by change from baseline to end of treatment in Bishop score v) 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 vi) Proportion of women with established labor ≤ 6 hours vii) Proportion of women with labor time ≤ 8 hours viii) Proportion of women with established labor ≥ 12 hours ix) Total dosages of study drug (IMP) x) Proportion of women with spontaneous labor (response group I) xi) Proportion of women with a ripe cervix (response group I+II) vii)xii) Proportion of women in response groups (I-IV)
Secondary Safety and tolerability endpoints include: i) Proportion of patients undergoing caesarean sections (CS) ii) Indications for CS iii) Proportion of patients undergoing instrumental deliveries (vacuum extraction (VE)/forceps delivery) iv) Indications for VE and forceps deliveries v) Fetal outcome measured as Birth weight, Apgar score, Acidosis (pH<7.10) and/or Base Excess < -12 mmol/L arterial or venous in umbilical cord blood vi) Indication for referral to neonatal intensive care unit (NICU) vii) Proportion of infants staying in the NICU for > 48 hours. viii) Uterine hyper stimulation in demand of tocolytic treatment ix) Proportion of patients with Postpartum Hemorrhage (PPH) > 2000 ml |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From start of treatment until discharge |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |