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

Phase 2
Completed
Conditions
Labor, Obstetric
Interventions
Registration Number
NCT03001193
Lead Sponsor
Dilafor AB
Brief Summary

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

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

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
361
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DF01 high doseDF 01The 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
DF01 low doseDF 01The 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
PL1PlaceboThe 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
DF01 medium doseDF 01The 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
DF01 low doseOxytocinThe 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
DF01 medium doseOxytocinThe 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
DF01 high doseOxytocinThe 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
PL1OxytocinThe 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
Primary Outcome Measures
NameTimeMethod
Time from start of infusion of tafoxiparin/placebo until vaginal partusInterval from start of study drug administration to vaginal delivery (hours, up to 36 hours )

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.

Secondary Outcome Measures
NameTimeMethod
Safety will be evaluated through rate and frequency of adverse events and serious adverse eventsThrough study completion ( 6 months, +/-4 weeks after delivery)

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

Time from cervical dilatation of 4 cm and progress of labor until vaginal partusInterval 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 partusInterval from start of study drug administration to vaginal delivery (hours, up to 36 hours )
Proportion of women with caesarean sectionsFrom start of study drug administration to caesarean section (hours, up to 36 hours)
Proportion of women undergoing instrumental deliveriesFrom 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 mlFrom 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 hoursFrom start of study drug administration and up to 7 days or discharge whichever comes first (days)
Uterine hyperstimulation with fetal heart rate changesFrom start of study drug administration to any delivery (hours, up to 36 hours)
Indication for referral to NICUFrom 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 responseFrom start of study drug administration to any delivery (hours, up to 36 hours)

Measurement of study drug in plasma at one time point

Trial Locations

Locations (12)

Kätilöopiston Sairaala (HUS)

🇫🇮

Helsinki, Finland

Tampere University Hospital

🇫🇮

Tampere, Finland

Naistenklinikka (HUS) Naistentaudit ja synnytykset

🇫🇮

Helsinki, Finland

Karlstad Kvinnokliniken Centralsjukhuset

🇸🇪

Karlstad, Sweden

Helsingborg Förlossningen, Helsingborgs Lasarett

🇸🇪

Helsingborg, Sweden

Länssjukhuset Ryhov

🇸🇪

Jonkoping, Sweden

Kvinnokliniken Universitesjukhuset

🇸🇪

Linkoping, Sweden

Kvinnokliniken Vrinnevisjukhuset

🇸🇪

Norrkoping, Sweden

Norra Älvsborgs Länssjukhus

🇸🇪

Trollhattan, Sweden

Akademiska sjukhuset

🇸🇪

Uppsala, Sweden

Hvidovre Hospital, Fødeafdelingen

🇩🇰

Hvidovre, Denmark

Skaraborgs sjukhus

🇸🇪

Skovde, Sweden

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