xml: <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/NCT06025916</url>
    </required_header>
    <id_info>
      <org_study_id>2022-00327</org_study_id>
      <nct_id>NCT06025916</nct_id>
    </id_info>
    <brief_title>Postpartum Hemorrhage Reduction With Oral Tranexamic Acid: a Clinical Trial</brief_title>
    <acronym>PROTECT</acronym>
    <official_title>Postpartum Hemorrhage Reduction With Oral Tranexamic Acid (PROTECT): a Multicenter Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Karolinska Institutet</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Stockholm South General Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>University of Cape Town</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Karolinska Institutet</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a multicentre randomized placebo-controlled double-blinded phase IV study among 1000&#xD;
        women in Sweden and South Africa on the effect of oral tranexamic acid on PPH after vaginal&#xD;
        delivery. The main purpose of the study is to evaluate the effect of orally administered&#xD;
        tranexamic acid (TA) compared to placebo on rate of postpartum hemorrhage (PPH) after vaginal&#xD;
        birth. Participants will be randomized to receive either 20 ml (2g) of the investigational&#xD;
        medicinal product (TA100mg/ml) or 20ml of a placebo solution during labor. Our main endpoint,&#xD;
        assessed at 24 hours after delivery is PPH defined as blood loss &gt;=500ml and assessed both by&#xD;
        weight and pre-postpartum hemoglobin (Hb) decrease &gt;10 units difference in vaginal deliveries&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background Severe PPH is the leading cause of maternal death worldwide especially in&#xD;
        developing countries. Preventing PPH before onset is of key importance because once bleeding&#xD;
        starts it is difficult to control.Tranexamic acid (TA) is a well-established medication for&#xD;
        treatment and prevention of heavy bleeding. Oral forms of TA are available over the counter&#xD;
        in many settings. The effect of oral treatment in vaginal deliveries has however been little&#xD;
        studied and is a stated research priority by the WHO. Oral TA is low-cost, stable at room&#xD;
        temperature and easy to administer which makes it especially applicable to both low resource&#xD;
        delivery settings and home- births.To prevent PPH, a therapeutic serum concentration of TA&#xD;
        should coincide with the period immediately after delivery of the child, when the risk of PPH&#xD;
        is greatest, meaning that TA should optimally be administered during the latter part of&#xD;
        active labor.&#xD;
  &#xD;
        The premises of the RCT are the following:&#xD;
  &#xD;
          1. The effect of oral prophylactic TA on rate of PPH is insufficiently known&#xD;
  &#xD;
          2. If oral TA is effective in preventing PPH, routine administration could reduce maternal&#xD;
             morbidity significantly at low expense.&#xD;
  &#xD;
        Methods Study population and inclusion criteria The study will include 1000 women planned for&#xD;
        vaginal delivery at three study sites in Sweden (n=500) and two study sites in South Africa&#xD;
        (n=500) during the period March 2023 to December 2026. Enrolled women will be ≥18 years, ≥36&#xD;
        gestational weeks, and planned for vaginal delivery. Women with known coagulation disorders,&#xD;
        known allergy to TA, ongoing treatment for venous thrombosis, or inability to make an&#xD;
        informed consent will be ineligible.&#xD;
  &#xD;
        Setting and duration: The study will take place between September 2023 and December 2026 at&#xD;
        three study sites in Sweden as well as Mowbray Maternity Hospital and Khayelitsha District&#xD;
        Hospital in South Africa.&#xD;
  &#xD;
        Recruitment and randomization We will recruit women during a routine or planned antenatal&#xD;
        visit after 35 gestational weeks, or after admission to the delivery ward during the latency&#xD;
        phase of labor or the early stages of labor.&#xD;
  &#xD;
        Randomization will occur after a woman has been admitted to the labor ward with spontaneous&#xD;
        onset of labor. Participants will be randomized to receive either 20 ml of the&#xD;
        investigational medicinal product (TA) or 20ml of a placebo solution. The randomization&#xD;
        sequence will be computer-generated by KTA (Karolinska Clinical Trial Alliance) and flasks&#xD;
        with the IMP/placebo will be marked according to this sequence. Randomization will be 1:1 in&#xD;
        permuted blocks of 10 to allow for block-sized deliveries to study sites. The placebo will be&#xD;
        developed and manufactured by Apotek Produktion och Laboratorier (APL), Sweden, who will also&#xD;
        supply the TA. Placebo and IMP flasks, in their randomization sequence will be transported in&#xD;
        a temperature-validated delivery to a central laboratory in Cape Town through World Courier&#xD;
        who specialises in research related distributions.&#xD;
  &#xD;
        Intervention Our intervention consists of the oral self-intake of either 20 ml (2g) of oral&#xD;
        solution of TA, 20 ml of placebo equivalent in appearance, odor and taste to the IMP, when&#xD;
        the cervix is fully dilated.&#xD;
  &#xD;
        Primary endpoints Weight-estimated rate of PPH (≥500ml)&#xD;
  &#xD;
        Secondary endpoints Pre-postpartum Hb difference (g/L) ≥10 units Weight-estimated rate of&#xD;
        severe PPH (≥1000ml) Mean blood loss (ml) Mean pre-postpartum Hb decrease (units Rate of&#xD;
        blood transfusion (%) Thromboembolism up to 6 weeks postpartum&#xD;
  &#xD;
        Study procedures Participants will experience three study procedures that would not&#xD;
        necessarily occur had they not taken part in the study but all of which form part of routine&#xD;
        care.&#xD;
  &#xD;
          1. A blood sample (hemoglobin, EVF, MCV, MCH, MCHC, LPC, TPC, APTT and INR) taken at&#xD;
             admission&#xD;
  &#xD;
          2. The oral intake of 20 ml IMP/placebo at full cervical dilatation&#xD;
  &#xD;
          3. Weighing of total blood loss (which is routine in many delivery settings)&#xD;
  &#xD;
          4. A blood sample including (hemoglobin, EVF, MCV, MCH, MCHC, LPC, TPC) taken after 24&#xD;
             hours (or prior to discharge should discharge occur before 24 hours)&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">March 2026</completion_date>
    <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
    <phase>Phase 4</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>Prevention</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>PPH</measure>
      <time_frame>24 hours</time_frame>
      <description>Weight-assessed blood loss after delivery &gt;/= 500ml</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Severe PPH</measure>
      <time_frame>24 hours</time_frame>
      <description>Blood loss after delivery &gt;/= 1000ml</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood transfusion</measure>
      <time_frame>72 hours</time_frame>
      <description>Need for blood transfusion after vaginal birth</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean blood loss</measure>
      <time_frame>24 hours</time_frame>
      <description>Mean blood loss after vaginal delivery (ml)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean pre-post partal hemoglobin</measure>
      <time_frame>24 hours</time_frame>
      <description>Mean pre-post partal hemoglobin difference (units)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pre-post partal hemoglobin</measure>
      <time_frame>24 hours</time_frame>
      <description>Pre-post partal hemoglobin &gt;/= 10 units</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Thromboembolism</measure>
      <time_frame>6 weeks after delivery</time_frame>
      <description>Thromboembolic event postpartum</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">1000</enrollment>
    <condition>PPH</condition>
    <arm_group>
      <arm_group_label>Tranexamic acid</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tranexamic acid</intervention_name>
      <description>20 ml of oral solution TA (100mg/ml)</description>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_label>Tranexamic acid</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Enrolled women will be ≥18 years, ≥36 gestational weeks, and planned for vaginal delivery.&#xD;
          Women with known coagulation disorders, known allergy to TA, ongoing treatment for venous&#xD;
          thrombosis, or inability to make an informed consent will be ineligible.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Opposite of above&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Margit Endler</last_name>
      <phone>0706747227</phone>
      <email>margit.endler@ki.se</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Helena Paul</last_name>
      <email>helena.paul@regionstockholm.se</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 29, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Karolinska Institutet</investigator_affiliation>
      <investigator_full_name>Margit Endler</investigator_full_name>
      <investigator_title>M.D. Associate Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Postpartum Hemorrhage</mesh_term>
      <mesh_term>Hemorrhage</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tranexamic Acid</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Anonymized research data will be made available upon reasonable request</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06025916
  org study id: 2022-00327
  nct id: NCT06025916
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This is a multicentre randomized placebo-controlled double-blinded phase IV study among 1000
        women in Sweden and South Africa on the effect of oral tranexamic acid on PPH after vaginal
        delivery. The main purpose of the study is to evaluate the effect of orally administered
        tranexamic acid (TA) compared to placebo on rate of postpartum hemorrhage (PPH) after vaginal
        birth. Participants will be randomized to receive either 20 ml (2g) of the investigational
        medicinal product (TA100mg/ml) or 20ml of a placebo solution during labor. Our main endpoint,
        assessed at 24 hours after delivery is PPH defined as blood loss >=500ml and assessed both by
        weight and pre-postpartum hemoglobin (Hb) decrease >10 units difference in vaginal deliveries
  Background Severe PPH is the leading cause of maternal death worldwide especially in
        developing countries. Preventing PPH before onset is of key importance because once bleeding
        starts it is difficult to control.Tranexamic acid (TA) is a well-established medication for
        treatment and prevention of heavy bleeding. Oral forms of TA are available over the counter
        in many settings. The effect of oral treatment in vaginal deliveries has however been little
        studied and is a stated research priority by the WHO. Oral TA is low-cost, stable at room
        temperature and easy to administer which makes it especially applicable to both low resource
        delivery settings and home- births.To prevent PPH, a therapeutic serum concentration of TA
        should coincide with the period immediately after delivery of the child, when the risk of PPH
        is greatest, meaning that TA should optimally be administered during the latter part of
        active labor.
  
        The premises of the RCT are the following:
  
          1. The effect of oral prophylactic TA on rate of PPH is insufficiently known
  
          2. If oral TA is effective in preventing PPH, routine administration could reduce maternal
             morbidity significantly at low expense.
  
        Methods Study population and inclusion criteria The study will include 1000 women planned for
        vaginal delivery at three study sites in Sweden (n=500) and two study sites in South Africa
        (n=500) during the period March 2023 to December 2026. Enrolled women will be ≥18 years, ≥36
        gestational weeks, and planned for vaginal delivery. Women with known coagulation disorders,
        known allergy to TA, ongoing treatment for venous thrombosis, or inability to make an
        informed consent will be ineligible.
  
        Setting and duration: The study will take place between September 2023 and December 2026 at
        three study sites in Sweden as well as Mowbray Maternity Hospital and Khayelitsha District
        Hospital in South Africa.
  
        Recruitment and randomization We will recruit women during a routine or planned antenatal
        visit after 35 gestational weeks, or after admission to the delivery ward during the latency
        phase of labor or the early stages of labor.
  
        Randomization will occur after a woman has been admitted to the labor ward with spontaneous
        onset of labor. Participants will be randomized to receive either 20 ml of the
        investigational medicinal product (TA) or 20ml of a placebo solution. The randomization
        sequence will be computer-generated by KTA (Karolinska Clinical Trial Alliance) and flasks
        with the IMP/placebo will be marked according to this sequence. Randomization will be 1:1 in
        permuted blocks of 10 to allow for block-sized deliveries to study sites. The placebo will be
        developed and manufactured by Apotek Produktion och Laboratorier (APL), Sweden, who will also
        supply the TA. Placebo and IMP flasks, in their randomization sequence will be transported in
        a temperature-validated delivery to a central laboratory in Cape Town through World Courier
        who specialises in research related distributions.
  
        Intervention Our intervention consists of the oral self-intake of either 20 ml (2g) of oral
        solution of TA, 20 ml of placebo equivalent in appearance, odor and taste to the IMP, when
        the cervix is fully dilated.
  
        Primary endpoints Weight-estimated rate of PPH (≥500ml)
  
        Secondary endpoints Pre-postpartum Hb difference (g/L) ≥10 units Weight-estimated rate of
        severe PPH (≥1000ml) Mean blood loss (ml) Mean pre-postpartum Hb decrease (units Rate of
        blood transfusion (%) Thromboembolism up to 6 weeks postpartum
  
        Study procedures Participants will experience three study procedures that would not
        necessarily occur had they not taken part in the study but all of which form part of routine
        care.
  
          1. A blood sample (hemoglobin, EVF, MCV, MCH, MCHC, LPC, TPC, APTT and INR) taken at
             admission
  
          2. The oral intake of 20 ml IMP/placebo at full cervical dilatation
  
          3. Weighing of total blood loss (which is routine in many delivery settings)
  
          4. A blood sample including (hemoglobin, EVF, MCV, MCH, MCHC, LPC, TPC) taken after 24
             hours (or prior to discharge should discharge occur before 24 hours)
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: Triple (Participant, Care Provider, Investigator)
  measure: PPH
  time frame: 24 hours
  description: Weight-assessed blood loss after delivery >/= 500ml
  measure: Severe PPH
  time frame: 24 hours
  description: Blood loss after delivery >/= 1000ml
  measure: Blood transfusion
  time frame: 72 hours
  description: Need for blood transfusion after vaginal birth
  measure: Mean blood loss
  time frame: 24 hours
  description: Mean blood loss after vaginal delivery (ml)
  measure: Mean pre-post partal hemoglobin
  time frame: 24 hours
  description: Mean pre-post partal hemoglobin difference (units)
  measure: Pre-post partal hemoglobin
  time frame: 24 hours
  description: Pre-post partal hemoglobin >/= 10 units
  measure: Thromboembolism
  time frame: 6 weeks after delivery
  description: Thromboembolic event postpartum
  arm group label: Tranexamic acid
  arm group type: Active Comparator
  arm group label: Placebo
  arm group type: Placebo Comparator
  intervention type: Drug
  intervention name: Tranexamic acid
  description: 20 ml of oral solution TA (100mg/ml)
  arm group label: Placebo
  arm group label: Tranexamic acid
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Margit Endler
  phone: 0706747227
  email: margit.endler@ki.se
  last name: Helena Paul
  email: helena.paul@regionstockholm.se
  responsible party type: Principal Investigator
  investigator affiliation: Karolinska Institutet
  investigator full name: Margit Endler
  investigator title: M.D. Associate Professor
  mesh term: Postpartum Hemorrhage
  mesh term: Hemorrhage
  mesh term: Tranexamic Acid
  sharing ipd: No
  ipd description: Anonymized research data will be made available upon reasonable request