<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/NCT03305263</url>
  </required_header>
  <id_info>
    <org_study_id>HCQDenmark</org_study_id>
    <secondary_id>2016-004981-24</secondary_id>
    <nct_id>NCT03305263</nct_id>
  </id_info>
  <brief_title>Hydroxychloroquine (HCQ) for Recurrent Pregnancy Loss</brief_title>
  <official_title>Hydroxycloroquin (Plaquenil) Behandling af Gentagne Graviditetstab (Abortus Habitualis) - et Randomiseret, Dobbeltblindet, Placebo Kontrolleret Studium</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rigshospitalet, Denmark</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recurrent pregnancy loss (RPL) defined as 3 or more pregnancy losses affects approximately 3%&#xD;
      of couples trying to achieve parenthood. Most cases of RPL are unexplained and have no&#xD;
      effective treatment to improve the chance of a live birth. Exciting indications for using&#xD;
      Hydroxychloroquine (HCQ) include: Malaria profylaxis and treatment, systemic and discoid&#xD;
      lupus erythematosus (SLE) and rheumatoid athritis (RA). HCQ has been reported to have the&#xD;
      following properties (anti-thrombotic, vascular-protective, immunomodulatory, improving&#xD;
      glucose tolerance, lipid-lowering, and anti-infectious).&#xD;
&#xD;
      There is no data concerning the benefit of HCQ in RPL. Administration for other indications&#xD;
      provides extensive safety data during pregnancy.&#xD;
&#xD;
      This study has the potential to establish support for a new treatment option for unexplained&#xD;
      RPL.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 25, 2018</start_date>
  <completion_date type="Anticipated">January 2023</completion_date>
  <primary_completion_date type="Anticipated">January 2022</primary_completion_date>
  <phase>Phase 3</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>Live birth</measure>
    <time_frame>At delivery</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Live birth after exclusion of patients with a chromosomal abnormal pregnancy loss, extrauterine pregnancy loss, intended abortion or patients with insufficient intake of study medicine</measure>
    <time_frame>At delivery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Birth weight</measure>
    <time_frame>At delivery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gestational age</measure>
    <time_frame>up to at delivery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Admittance to neonatal unit</measure>
    <time_frame>Within 28 days of delivery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological status</measure>
    <time_frame>Up to two years after end of study</time_frame>
    <description>Measuements of celllur and humoral immunity</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">186</enrollment>
  <condition>Recurrent Pregnancy Loss</condition>
  <arm_group>
    <arm_group_label>Hydroxychlorochine HCQ</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Women in the experimental arm will take 200 mg HCQ tablets every day, starting minimum 2 months (recommended 3-6) prior to conception and continuing until 28 weeks of pregnancy or until the pregnancy is over.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hydroxychlorochine HCQ Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Women in the experimental arm will take 200 mg HCQ placebo tablets every day, starting minimum 2 months (recommended 3-6) prior to conception and continuing until 28 weeks of pregnancy or until the pregnancy is over.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine</intervention_name>
    <description>One tablet a day from inclusion until end of pregnancy or gestational age 28</description>
    <arm_group_label>Hydroxychlorochine HCQ</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine placebo</intervention_name>
    <description>One tablet a day from inclusion until end of pregnancy or gestational age 28</description>
    <arm_group_label>Hydroxychlorochine HCQ Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ≥ 4 confirmed consecutive pregnancy losses prior to gestational age 22+0 in women with&#xD;
             unexplained RPL&#xD;
&#xD;
          2. ≥ 3 confirmed consecutive pregnancy losses prior to gestational age 22+0 in women with&#xD;
             unexplained RPL with minimum one second trimester loss.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age below 18 years or above 39 at inclusion&#xD;
&#xD;
          2. Abnomal uterine anatomi at hysterosalpingography/hysteroscopy or hydrosonography&#xD;
&#xD;
          3. Chromosomal abnormalities within the couple&#xD;
&#xD;
          4. Menstrual cycle below 23 days or above 35 days&#xD;
&#xD;
          5. Lupusantikoagulans positivity or immunoglobulin (Ig)G/IgM anticardiolipinantibodies&#xD;
             (≥10 GPL kU/l at Rigshospitalets Laboratorium) or plasma homocystein ≥25 mikrogr./l at&#xD;
             repeated measurement with 12 weeks interval.&#xD;
&#xD;
          6. HIV or Hepatitis B or C positive&#xD;
&#xD;
          7. Psoriasis, retinopathy og serious imparied hearing (Contraindications for HCQ)&#xD;
&#xD;
          8. Chronic disease that lead to intake of immunemodulatory drugs or potentially pregnancy&#xD;
             toxic agents&#xD;
&#xD;
          9. Hemoglobin ≤ 6.5 mmol/L, leukocytes &lt;3.5 E9/L, platelets &lt;145 E9/L at inclusion&#xD;
&#xD;
         10. Previous treatment with HCQ in pregnancy&#xD;
&#xD;
         11. &gt;1previous live birth&#xD;
&#xD;
         12. previous participation in this trial&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>39 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Henriette Svarre Nielsen, MD, DMSc</last_name>
    <phone>+4535457515</phone>
    <email>henriette.svarre.nielsen@regionh.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Louise Lunøe, Nurse</last_name>
    <phone>+4535458486</phone>
    <email>anne.louise.lunoee@regionh.dk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>København</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Louise Lunøe, Nurse</last_name>
      <phone>+4535458486</phone>
      <email>anne.louise.lunoee@regionh.dk</email>
    </contact>
    <contact_backup>
      <last_name>Henriette S Nielsen, MD</last_name>
      <phone>+4535457515</phone>
      <email>henriette.svarre.nielsen@regionh.dk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>October 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 9, 2017</study_first_posted>
  <last_update_submitted>March 11, 2020</last_update_submitted>
  <last_update_submitted_qc>March 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Henriette Svarre Nielsen, MD, DMSc</investigator_full_name>
    <investigator_title>Consultant, Head of Recurrent Pregnancy Loss Unit, Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Abortion, Habitual</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03305263
org study id: HCQDenmark
secondary id: 2016-004981-24
nct id: NCT03305263
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Recurrent pregnancy loss (RPL) defined as 3 or more pregnancy losses affects approximately 3%
      of couples trying to achieve parenthood. Most cases of RPL are unexplained and have no
      effective treatment to improve the chance of a live birth. Exciting indications for using
      Hydroxychloroquine (HCQ) include: Malaria profylaxis and treatment, systemic and discoid
      lupus erythematosus (SLE) and rheumatoid athritis (RA). HCQ has been reported to have the
      following properties (anti-thrombotic, vascular-protective, immunomodulatory, improving
      glucose tolerance, lipid-lowering, and anti-infectious).

      There is no data concerning the benefit of HCQ in RPL. Administration for other indications
      provides extensive safety data during pregnancy.

      This study has the potential to establish support for a new treatment option for unexplained
      RPL.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Live birth
time frame: At delivery
measure: Live birth after exclusion of patients with a chromosomal abnormal pregnancy loss, extrauterine pregnancy loss, intended abortion or patients with insufficient intake of study medicine
time frame: At delivery
measure: Birth weight
time frame: At delivery
measure: Gestational age
time frame: up to at delivery
measure: Admittance to neonatal unit
time frame: Within 28 days of delivery
measure: Immunological status
time frame: Up to two years after end of study
description: Measuements of celllur and humoral immunity
arm group label: Hydroxychlorochine HCQ
arm group type: Experimental
description: Women in the experimental arm will take 200 mg HCQ tablets every day, starting minimum 2 months (recommended 3-6) prior to conception and continuing until 28 weeks of pregnancy or until the pregnancy is over.
arm group label: Hydroxychlorochine HCQ Placebo
arm group type: Placebo Comparator
description: Women in the experimental arm will take 200 mg HCQ placebo tablets every day, starting minimum 2 months (recommended 3-6) prior to conception and continuing until 28 weeks of pregnancy or until the pregnancy is over.
intervention type: Drug
intervention name: Hydroxychloroquine
description: One tablet a day from inclusion until end of pregnancy or gestational age 28
arm group label: Hydroxychlorochine HCQ
other name: Placebo
intervention type: Drug
intervention name: Hydroxychloroquine placebo
description: One tablet a day from inclusion until end of pregnancy or gestational age 28
arm group label: Hydroxychlorochine HCQ Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 39 Years
healthy volunteers: No
last name: Henriette Svarre Nielsen, MD, DMSc
phone: +4535457515
email: henriette.svarre.nielsen@regionh.dk
last name: Louise Lunøe, Nurse
phone: +4535458486
email: anne.louise.lunoee@regionh.dk
facility: 
status: Recruiting
contact: 
contact backup: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Henriette Svarre Nielsen, MD, DMSc
investigator title: Consultant, Head of Recurrent Pregnancy Loss Unit, Associate Professor
mesh term: Abortion, Habitual
mesh term: Hydroxychloroquine
sharing ipd: Undecided