Effect of Tafoxiparin to Treat Primary Slow Progress of Labor Including Prolonged Latent Phase and Labor Arrest

Study Overview
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Brief Summary
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The study will be designed as a double-blind, placebo-controlled, parallel-group, dose-finding study with one group treated with placebo and three groups treated with tafoxiparin in three different infusion concentration levels, respectively. The intravenous infusion will be initiated by a pre-defined bolus dose infusion.

Detailed Description
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Primary objective To assess the dose-response relationship of tafoxiparin on the labor time defined as the time from the start of continuous infusion of tafoxiparin/placebo as an Adjunct Treatment to Oxytocin, until partus in term-pregnant, nulliparous women requiring labor augmentation due to Primary Slow Progress of Labor including prolonged latent phase and Labor Arrest. Secondary objectives To assess the safety and efficacy of tafoxiparin based on the safety and secondary efficacy parameters evaluated in the protocol. PK (pharmacokinetic) response in pregnant women during labor. Methodology All term-pregnant, nulliparous women presenting to the delivery ward are potential study patients unless they have already been enrolled in another clinical study. Subjects may be pre-informed about the study through the use of advertisements or information at the physician/midwife visits during pregnancy and at hospital admission. The whole study includes the following steps: Screening and Baseline including informed consent and randomization Labor Discharge Follow-up at 8 (+/-1)weeks - End of study Safety follow up of infant at 6 months, +/-4 weeks, by telephone interview

Official Title
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Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Finding Study to Evaluate the Effect of Continuous Infusion of Tafoxiparin as an Adjunct Treatment to Oxytocin for up to 36 Hours in Term Pregnant, Nulliparous Women to Treat Primary Slow Progress of Labor Including Prolonged Latent Phase and Labor Arrest

Conditions
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Labor, Obstetric

Intervention / Treatment
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* Drug: DF 01
* Drug: Oxytocin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women of ≥18 to ≤45 years of age Nulliparous Gestational age > 36 weeks + 6 days confirmed by ultrasound Experience slow progress of labor including prolonged latent phase and labor arrest (according to the respective definitions) etc Exclusion Criteria: Subjects with secondary slow progress or secondary labor arrest BMI≥35 during first trimester of pregnancy Breech presentation or other abnormal presentations etc

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DF01 low dose<br>The subjects will receive intravenous infusion of DF01 (tafoxiparin) in low dose as an Adjunct Treatment to Oxytocin for up to 36 hours initiated by a pre-defined bolus dose as a therapeutic intervention until delivery | Drug: DF 01<br> <br> * Other names: Tafoxiparin;Drug: Oxytocin<br> <br> |
| Experimental: DF01 medium dose<br>The subjects will receive intravenous infusion of DF01 (tafoxiparin) in medium dose as an Adjunct Treatment to Oxytocin for up to 36 hours initiated by a pre-defined bolus dose as a therapeutic intervention until delivery | Drug: DF 01<br> <br> * Other names: Tafoxiparin;Drug: Oxytocin<br> <br> |
| Experimental: DF01 high dose<br>The subjects will receive intravenous infusion of DF01 (tafoxiparin) in high dose as an Adjunct Treatment to Oxytocin for up to 36 hours initiated by a pre-defined bolus dose as a therapeutic intervention until delivery | Drug: DF 01<br> <br> * Other names: Tafoxiparin;Drug: Oxytocin<br> <br> |
| Placebo Comparator: PL1<br>The subjects will receive intravenous infusion of placebo as an Adjunct Treatment to Oxytocin for up to 36 hours initiated by a pre-defined bolus dose as a therapeutic intervention until delivery | Drug: Oxytocin<br> <br> Drug: Placebo<br> <br> * Other names: PL1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from start of infusion of tafoxiparin/placebo until vaginal partus | The primary endpoint (time from first infusion to vaginal partus) will be summarized graphically for each treatment group using Kaplan-Meier estimates. In addition to this statistical comparison between the treatments will be performed using the analysis of variance technique. | Interval from start of study drug administration to vaginal delivery (hours, up to 36 hours ) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety will be evaluated through rate and frequency of adverse events and serious adverse events | Safety will be evaluated through rate and frequency of adverse events and serious adverse events, complete and symptom-directed physical evaluations, vital signs, safety blood samples (hematology and clinical chemistry), and rate of withdrawals from the study and/or the study medication | Through study completion ( 6 months, +/-4 weeks after delivery) | 
| Time from cervical dilatation of 4 cm and progress of labor until vaginal partus |  | Interval from 4 cm of cervical dilatation to vaginal delivery (hours, up to 36 hours ) | 
| Proportion of women with dystocia/protracted labor defined as ≥8, 10, 12 and 14 hours of established labor (4 cm of cervical dilation to vaginal partus ) |  | Interval from 4 cm of cervical dilatation to vaginal delivery (hours, up to 36 hours ) | 
| Proportion of women with dystocia/protracted labor defined as ≥8, 10, 12 and 14 hours from start of study drug infusion to vaginal partus |  | Interval from start of study drug administration to vaginal delivery (hours, up to 36 hours ) | 
| Proportion of women with caesarean sections |  | From start of study drug administration to caesarean section (hours, up to 36 hours) | 
| Proportion of women undergoing instrumental deliveries |  | From start of study drug administration to instrumental delivery (hours, up to 36 hours) | 
| Use of analgesia (N2O, epidural, pudendal nerve block) |  | From start of study drug administration to any delivery (hours, up to 36 hours) | 
| Proportion of women with postpartum hemorrhage > 1000 ml |  | From start of study drug administration and up to 7 days or discharge whichever comes first (days) | 
| Fetal outcome measured as Apgar score (5 min) ≤ 7 points, Base Excess > -12 and referral to NICU (neonatal intensive care unit) (for > 48 hours |  | From start of study drug administration and up to 7 days or discharge whichever comes first (days) | 
| Uterine hyperstimulation with fetal heart rate changes |  | From start of study drug administration to any delivery (hours, up to 36 hours) | 
| Indication for referral to NICU |  | From start of study drug administration through study completion (6 months +- 4 weeks after delivery) | 
| Use of Oxytocin (no. of mls. according to instructions) |  | From start of study drug administration to any delivery (hours, up to 36 hours) | 
| Pharmacokinetic response | Measurement of study drug in plasma at one time point | From start of study drug administration to any delivery (hours, up to 36 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary slow progress, Prolonged latent phase, Labor arrest