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

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

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.

Study Overview

• Status: Completed
• Conditions: Labor, Obstetric
• Intervention / Treatment: Drug: Placebo; Drug: Oxytocin; Drug: DF 01

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 361
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital, Fødeafdelingen
• Finland
  • Helsinki, Finland, 00029
    • Naistenklinikka (HUS) Naistentaudit ja synnytykset
  • Helsinki, Finland, 00610
    • Kätilöopiston Sairaala (HUS)
  • Tampere, Finland, 33521
    • Tampere University Hospital
• Sweden
  • Helsingborg, Sweden, 25187
    • Helsingborg Förlossningen, Helsingborgs Lasarett
  • Jonkoping, Sweden, 55305
    • Lanssjukhuset Ryhov
  • Karlstad, Sweden, 65230
    • Karlstad Kvinnokliniken Centralsjukhuset
  • Linkoping, Sweden, 58185
    • Kvinnokliniken Universitesjukhuset
  • Norrkoping, Sweden, 60182
    • Kvinnokliniken Vrinnevisjukhuset
  • Skovde, Sweden, 54185
    • Skaraborgs sjukhus
  • Trollhattan, Sweden, 46173
    • Norra Älvsborgs Länssjukhus
  • Uppsala, Sweden, 75185
    • Akademiska Sjukhuset

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Pregnant women of ≥18 to ≤45 years of age
2. Nulliparous
3. Gestational age > 36 weeks + 6 days confirmed by ultrasound
4. Experience slow progress of labor including prolonged latent phase and labor arrest (according to the respective definitions) etc

Exclusion Criteria:

1. Subjects with secondary slow progress or secondary labor arrest
2. BMI≥35 during first trimester of pregnancy
3. Breech presentation or other abnormal presentations etc

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DF01 low dose; 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: Oxytocin; Drug: DF 01; Other Names: Tafoxiparin
Experimental: DF01 medium dose; 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: Oxytocin; Drug: DF 01; Other Names: Tafoxiparin
Experimental: DF01 high dose; 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: Oxytocin; Drug: DF 01; Other Names: Tafoxiparin
Placebo Comparator: PL1; 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: Placebo; Other Names: PL1; Drug: Oxytocin

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Dilafor AB
• Investigators: Study Chair: Gunvor Ekman-Ordeberg, MD, PhD, Dilafor AB

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: December 6, 2016
• First Submitted That Met QC Criteria: December 20, 2016
• First Posted (Estimate): December 22, 2016

Study Record Updates

• Last Update Posted (Actual): April 29, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Primary slow progress; Prolonged latent phase; Labor arrest
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: PPL07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No