<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03001193</url>
  </required_header>
  <id_info>
    <org_study_id>PPL07</org_study_id>
    <nct_id>NCT03001193</nct_id>
  </id_info>
  <brief_title>Effect of Tafoxiparin to Treat Primary Slow Progress of Labor Including Prolonged Latent Phase and Labor Arrest</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dilafor AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dilafor AB</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study will be designed as a double-blind, placebo-controlled, parallel-group,&#xD;
      dose-finding study with one group treated with placebo and three groups treated with&#xD;
      tafoxiparin in three different infusion concentration levels, respectively. The intravenous&#xD;
      infusion will be initiated by a pre-defined bolus dose infusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary objective&#xD;
&#xD;
      To assess the dose-response relationship of tafoxiparin on the labor time defined as the time&#xD;
      from the start of continuous infusion of tafoxiparin/placebo as an Adjunct Treatment to&#xD;
      Oxytocin, until partus in term-pregnant, nulliparous women requiring labor augmentation due&#xD;
      to Primary Slow Progress of Labor including prolonged latent phase and Labor Arrest.&#xD;
&#xD;
      Secondary objectives&#xD;
&#xD;
      To assess the safety and efficacy of tafoxiparin based on the safety and secondary efficacy&#xD;
      parameters evaluated in the protocol. PK (pharmacokinetic) response in pregnant women during&#xD;
      labor.&#xD;
&#xD;
      Methodology&#xD;
&#xD;
      All term-pregnant, nulliparous women presenting to the delivery ward are potential study&#xD;
      patients unless they have already been enrolled in another clinical study. Subjects may be&#xD;
      pre-informed about the study through the use of advertisements or information at the&#xD;
      physician/midwife visits during pregnancy and at hospital admission.&#xD;
&#xD;
      The whole study includes the following steps:&#xD;
&#xD;
        -  Screening and Baseline including informed consent and randomization&#xD;
&#xD;
        -  Labor&#xD;
&#xD;
        -  Discharge&#xD;
&#xD;
        -  Follow-up at 8 (+/-1)weeks - End of study&#xD;
&#xD;
        -  Safety follow up of infant at 6 months, +/-4 weeks, by telephone interview&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Actual">May 2019</completion_date>
  <primary_completion_date type="Actual">November 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time from start of infusion of tafoxiparin/placebo until vaginal partus</measure>
    <time_frame>Interval from start of study drug administration to vaginal delivery (hours, up to 36 hours )</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety will be evaluated through rate and frequency of adverse events and serious adverse events</measure>
    <time_frame>Through study completion ( 6 months, +/-4 weeks after delivery)</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from cervical dilatation of 4 cm and progress of labor until vaginal partus</measure>
    <time_frame>Interval from 4 cm of cervical dilatation to vaginal delivery (hours, up to 36 hours )</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <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 )</measure>
    <time_frame>Interval from 4 cm of cervical dilatation to vaginal delivery (hours, up to 36 hours )</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <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</measure>
    <time_frame>Interval from start of study drug administration to vaginal delivery (hours, up to 36 hours )</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of women with caesarean sections</measure>
    <time_frame>From start of study drug administration to caesarean section (hours, up to 36 hours)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of women undergoing instrumental deliveries</measure>
    <time_frame>From start of study drug administration to instrumental delivery (hours, up to 36 hours)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of analgesia (N2O, epidural, pudendal nerve block)</measure>
    <time_frame>From start of study drug administration to any delivery (hours, up to 36 hours)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of women with postpartum hemorrhage &gt; 1000 ml</measure>
    <time_frame>From start of study drug administration and up to 7 days or discharge whichever comes first (days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fetal outcome measured as Apgar score (5 min) ≤ 7 points, Base Excess &gt; -12 and referral to NICU (neonatal intensive care unit) (for &gt; 48 hours</measure>
    <time_frame>From start of study drug administration and up to 7 days or discharge whichever comes first (days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Uterine hyperstimulation with fetal heart rate changes</measure>
    <time_frame>From start of study drug administration to any delivery (hours, up to 36 hours)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Indication for referral to NICU</measure>
    <time_frame>From start of study drug administration through study completion (6 months +- 4 weeks after delivery)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of Oxytocin (no. of mls. according to instructions)</measure>
    <time_frame>From start of study drug administration to any delivery (hours, up to 36 hours)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic response</measure>
    <time_frame>From start of study drug administration to any delivery (hours, up to 36 hours)</time_frame>
    <description>Measurement of study drug in plasma at one time point</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">361</enrollment>
  <condition>Labor, Obstetric</condition>
  <arm_group>
    <arm_group_label>DF01 low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DF01 medium dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DF01 high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PL1</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DF 01</intervention_name>
    <arm_group_label>DF01 high dose</arm_group_label>
    <arm_group_label>DF01 low dose</arm_group_label>
    <arm_group_label>DF01 medium dose</arm_group_label>
    <other_name>Tafoxiparin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxytocin</intervention_name>
    <arm_group_label>DF01 high dose</arm_group_label>
    <arm_group_label>DF01 low dose</arm_group_label>
    <arm_group_label>DF01 medium dose</arm_group_label>
    <arm_group_label>PL1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>PL1</arm_group_label>
    <other_name>PL1</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pregnant women of ≥18 to ≤45 years of age&#xD;
&#xD;
          2. Nulliparous&#xD;
&#xD;
          3. Gestational age &gt; 36 weeks + 6 days confirmed by ultrasound&#xD;
&#xD;
          4. Experience slow progress of labor including prolonged latent phase and labor arrest&#xD;
             (according to the respective definitions) etc&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with secondary slow progress or secondary labor arrest&#xD;
&#xD;
          2. BMI≥35 during first trimester of pregnancy&#xD;
&#xD;
          3. Breech presentation or other abnormal presentations etc&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gunvor Ekman-Ordeberg, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Dilafor AB</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hvidovre Hospital, Fødeafdelingen</name>
      <address>
        <city>Hvidovre</city>
        <zip>2650</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Naistenklinikka (HUS) Naistentaudit ja synnytykset</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kätilöopiston Sairaala (HUS)</name>
      <address>
        <city>Helsinki</city>
        <zip>00610</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tampere University Hospital</name>
      <address>
        <city>Tampere</city>
        <zip>33521</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helsingborg Förlossningen, Helsingborgs Lasarett</name>
      <address>
        <city>Helsingborg</city>
        <zip>25187</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Länssjukhuset Ryhov</name>
      <address>
        <city>Jonkoping</city>
        <zip>55305</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karlstad Kvinnokliniken Centralsjukhuset</name>
      <address>
        <city>Karlstad</city>
        <zip>65230</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kvinnokliniken Universitesjukhuset</name>
      <address>
        <city>Linkoping</city>
        <zip>58185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kvinnokliniken Vrinnevisjukhuset</name>
      <address>
        <city>Norrkoping</city>
        <zip>60182</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skaraborgs sjukhus</name>
      <address>
        <city>Skovde</city>
        <zip>54185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norra Älvsborgs Länssjukhus</name>
      <address>
        <city>Trollhattan</city>
        <zip>46173</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akademiska sjukhuset</name>
      <address>
        <city>Uppsala</city>
        <zip>75185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Finland</country>
    <country>Sweden</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 22, 2016</study_first_posted>
  <last_update_submitted>April 28, 2020</last_update_submitted>
  <last_update_submitted_qc>April 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Primary slow progress</keyword>
  <keyword>Prolonged latent phase</keyword>
  <keyword>Labor arrest</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxytocin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03001193
org study id: PPL07
nct id: NCT03001193
lead sponsor: 
has dmc: No
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.
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time from start of infusion of tafoxiparin/placebo until vaginal partus
time frame: Interval from start of study drug administration to vaginal delivery (hours, up to 36 hours )
description: 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.
measure: Safety will be evaluated through rate and frequency of adverse events and serious adverse events
time frame: Through study completion ( 6 months, +/-4 weeks after delivery)
description: 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
measure: Time from cervical dilatation of 4 cm and progress of labor until vaginal partus
time frame: 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 )
time frame: 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
time frame: Interval from start of study drug administration to vaginal delivery (hours, up to 36 hours )
measure: Proportion of women with caesarean sections
time frame: From start of study drug administration to caesarean section (hours, up to 36 hours)
measure: Proportion of women undergoing instrumental deliveries
time frame: From start of study drug administration to instrumental delivery (hours, up to 36 hours)
measure: Use of analgesia (N2O, epidural, pudendal nerve block)
time frame: From start of study drug administration to any delivery (hours, up to 36 hours)
measure: Proportion of women with postpartum hemorrhage > 1000 ml
time frame: 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
time frame: 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
time frame: From start of study drug administration to any delivery (hours, up to 36 hours)
measure: Indication for referral to NICU
time frame: 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)
time frame: From start of study drug administration to any delivery (hours, up to 36 hours)
measure: Pharmacokinetic response
time frame: From start of study drug administration to any delivery (hours, up to 36 hours)
description: Measurement of study drug in plasma at one time point
arm group label: DF01 low dose
arm group type: Experimental
description: 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
arm group label: DF01 medium dose
arm group type: Experimental
description: 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
arm group label: DF01 high dose
arm group type: Experimental
description: 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
arm group label: PL1
arm group type: Placebo Comparator
description: 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
intervention type: Drug
intervention name: DF 01
arm group label: DF01 high dose
arm group label: DF01 low dose
arm group label: DF01 medium dose
other name: Tafoxiparin
intervention type: Drug
intervention name: Oxytocin
arm group label: DF01 high dose
arm group label: DF01 low dose
arm group label: DF01 medium dose
arm group label: PL1
intervention type: Drug
intervention name: Placebo
arm group label: PL1
other name: PL1
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Gunvor Ekman-Ordeberg, MD, PhD
role: Study Chair
affiliation: Dilafor AB
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
country: Finland
country: Sweden
responsible party type: Sponsor
mesh term: Oxytocin
sharing ipd: No