Clinical trial NCT03001193: Effect of Tafoxiparin to Treat Primary Slow Progress of Labor Including Prolonged Latent Phase and Labor Arrest
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Labor, Obstetric
Keywords: Primary slow progress
Prolonged latent phase
Labor arrest
Lead sponsor: Dilafor AB
Sponsor class: INDUSTRY
First posted: 2016-12-22
Enrollment: 361
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Time from start of infusion of tafoxiparin/placebo until vaginal partus
timeFrame: Interval from start of study drug administration to vaginal delivery (hours, up to 36 hours )
Secondary outcomes:
measure: Safety will be evaluated through rate and frequency of adverse events and serious adverse events
timeFrame: Through study completion ( 6 months, +/-4 weeks after delivery)
measure: Time from cervical dilatation of 4 cm and progress of labor until vaginal partus
timeFrame: Interval from 4 cm of cervical dilatation to vaginal delivery (hours, up to 36 hours )
measure: 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 )
timeFrame: Interval from 4 cm of cervical dilatation to vaginal delivery (hours, up to 36 hours )
measure: Proportion of women with dystocia/protracted labor defined as ≥8, 10, 12 and 14 hours from start of study drug infusion to vaginal partus
timeFrame: Interval from start of study drug administration to vaginal delivery (hours, up to 36 hours )
measure: Proportion of women with caesarean sections
timeFrame: From start of study drug administration to caesarean section (hours, up to 36 hours)
measure: Proportion of women undergoing instrumental deliveries
timeFrame: From start of study drug administration to instrumental delivery (hours, up to 36 hours)
measure: Use of analgesia (N2O, epidural, pudendal nerve block)
timeFrame: From start of study drug administration to any delivery (hours, up to 36 hours)
measure: Proportion of women with postpartum hemorrhage > 1000 ml
timeFrame: From start of study drug administration and up to 7 days or discharge whichever comes first (days)
measure: Fetal outcome measured as Apgar score (5 min) ≤ 7 points, Base Excess > -12 and referral to NICU (neonatal intensive care unit) (for > 48 hours
timeFrame: From start of study drug administration and up to 7 days or discharge whichever comes first (days)
measure: Uterine hyperstimulation with fetal heart rate changes
timeFrame: From start of study drug administration to any delivery (hours, up to 36 hours)
measure: Indication for referral to NICU
timeFrame: From start of study drug administration through study completion (6 months +- 4 weeks after delivery)
measure: Use of Oxytocin (no. of mls. according to instructions)
timeFrame: From start of study drug administration to any delivery (hours, up to 36 hours)
measure: Pharmacokinetic response
timeFrame: From start of study drug administration to any delivery (hours, up to 36 hours)
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital, Fødeafdelingen
city: Helsinki
country: Finland
facility: Naistenklinikka (HUS) Naistentaudit ja synnytykset
city: Helsinki
country: Finland
facility: Kätilöopiston Sairaala (HUS)
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Helsingborg
country: Sweden
facility: Helsingborg Förlossningen, Helsingborgs Lasarett
city: Jonkoping
country: Sweden
facility: Länssjukhuset Ryhov
city: Karlstad
country: Sweden
facility: Karlstad Kvinnokliniken Centralsjukhuset
city: Linkoping
country: Sweden
facility: Kvinnokliniken Universitesjukhuset
city: Norrkoping
country: Sweden
facility: Kvinnokliniken Vrinnevisjukhuset
city: Skovde
country: Sweden
facility: Skaraborgs sjukhus
city: Trollhattan
country: Sweden
facility: Norra Älvsborgs Länssjukhus
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
Study officials:
affiliation: Dilafor AB
name: Gunvor Ekman-Ordeberg, MD, PhD
role: STUDY_CHAIR
References: