<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/NCT04410562</url>
  </required_header>
  <id_info>
    <org_study_id>2020-001587-29</org_study_id>
    <nct_id>NCT04410562</nct_id>
  </id_info>
  <brief_title>Hydroxychloroquine Efficacy and Safety in Preventing SARS-CoV-2 Infection and COVID-19 Disease Severity During Pregnancy and Postpartum</brief_title>
  <acronym>COVID-Preg</acronym>
  <official_title>Hydroxychloroquine Efficacy and Safety in Preventing SARS-CoV-2 Infection and COVID-19 Disease Severity During Pregnancy and Postpartum</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Barcelona Institute for Global Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital Clinic of Barcelona</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital of Torrejon</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fundación de investigación HM</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Sant Joan de Deu</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital del Mar</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Universitario Infanta Leonor</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Universitario Fundación Alcorcón</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital General de Segovia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut Català de la Salut</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Barcelona Institute for Global Health</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>
      It still unclear how SARS-CoV-2 affects pregnant women and their offspring, as well as which&#xD;
      factors may influence obstetrical disease and outcomes, including the timing of maternal&#xD;
      viral exposure by gestational age, the effects of parity, age, host immune responses,&#xD;
      coexisting medical and obstetrical conditions and the effects of treatment regimens. While&#xD;
      further information is gathered, based on the existing evidence from other infections causing&#xD;
      pneumonia, pregnant women should be considered to be at high risk for developing severe&#xD;
      infection during the current COVID-19 epidemic. Results from clinical trials with HCQ in&#xD;
      nonpregnant adults may not be directly extrapolated to pregnant women given the special&#xD;
      features of the pregnancy status. Thus, clinical research is urgently needed to improve the&#xD;
      care and reduce the risk of poor pregnancy outcomes of women in this and in future epidemics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double blinded, placebo-controlled multicenter clinical trial including&#xD;
      714 pregnant women (200 SARS-CoV-2 infected -100 symptomatic with mild disease and 100&#xD;
      asymptomatic- pregnant women and 514 SARS-CoV-2 uninfected pregnant women who are contacts&#xD;
      with a SARS-CoV-2 case) with the main objectives of assessing the safety and efficacy of oral&#xD;
      hydroxychloroquine (HCQ) in reducing maternal viral shedding by PCR, and preventing incident&#xD;
      SARS-CoV-2 infection and disease severity. Pregnant women undergoing antenatal follow up at&#xD;
      five maternity hospitals, presenting at least one sign and/or one mild suggestive symptoms&#xD;
      and a positive SARS-CoV-2 PCR test, or who are contacts of a suspected or confirmed case,&#xD;
      will be recruited and randomized 1:1 to receive HCQ orally (400 mg/day for 3 days, followed&#xD;
      by 200 mg/day for 11 days) or placebo. Women will be followed up for the duration of the&#xD;
      intervention. One week after intervention completion, a SARS-CoV-2 PCR test will be repeated.&#xD;
      At delivery, the pregnancy outcome will be registered, and a cord blood sample will be&#xD;
      collected to measure for IgG and IgM of SARS-CoV-2. A neonatal nasopharyngeal aspirate will&#xD;
      be collected to perform PCR SARS-CoV-2 testing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 13, 2020</start_date>
  <completion_date type="Actual">October 31, 2021</completion_date>
  <primary_completion_date type="Actual">June 30, 2021</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>
    <intervention_model_description>Randomized, double-blinded, placebo-controlled multicentre clinical trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of PCR confirmed cases among pregnant women</measure>
    <time_frame>21 days after intervention</time_frame>
    <description>Number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of COVID-19 disease during pregnancy</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of COVID-19-related admissions</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of all-cause admissions</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of all-cause outpatient attendances</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean duration of symptoms-signs of COVID-19</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency and severity of adverse events</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of preeclampsia</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of gestational diabetes</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of SARS-CoV-2 infections during pregnancy</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of intrauterine growth restriction</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal mortality rate</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of neonates with SARS-CoV-2- intrauterine infection by PCR-confirmed SARS-CoV-2-infection in nasopharyngeal aspirate.</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of neonates with clinical signs/symptoms of COVID-19</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of low birth weight (&lt;10th centile according to local standards)</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of preterm birth (&lt;37 weeks of gestational age)</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of embryo and foetal losses (miscarriages and stillbirths)</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of congenital malformations</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of adverse perinatal outcome</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal morbidity</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal mortality rate</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">129</enrollment>
  <condition>Pregnancy Related</condition>
  <condition>COVID</condition>
  <condition>Covid-19</condition>
  <arm_group>
    <arm_group_label>Hydroxychloroquine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be then randomized in a 1:1 ratio to HCQ (400 mg/day for three days, followed by 200 mg/day for 11 days)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be then randomized in a 1:1 ratio to placebo (2 tablets for three days, followed by one tablet for 11 days).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine</intervention_name>
    <description>Participants will receive a bottle containing 19 tablets of study medication. They will be instructed to take two tablets for the first three days and one tablet for the following 11 days. (400 mg/day for three days, followed by 200 mg/day for 11 days).</description>
    <arm_group_label>Hydroxychloroquine</arm_group_label>
    <other_name>Dolquine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive a bottle containing 19 tablets of placebo. They will be instructed to take two tablets for the first three days and one tablet for the following 11 days.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Presenting with fever (≥37.5ºC) and/or one mild symptom suggestive of COVID-19 disease&#xD;
             (cough, dyspnoea, chills, odynophagia, diarrhoea, muscle pain, anosmia, taste&#xD;
             disorder, headache) OR contact of a SARS-CoV-2 confirmed or suspected case in the past&#xD;
             14 days&#xD;
&#xD;
          -  More than 12 weeks of gestation (dated by ultrasonography)&#xD;
&#xD;
          -  Agreement to deliver in the study hospitals&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hypersensitivity to HCQ or other 4-aminoquinoline compounds&#xD;
&#xD;
          -  History of retinopathy of any aetiology&#xD;
&#xD;
          -  Concomitant use of digoxin, cyclosporine, cimetidine&#xD;
&#xD;
          -  Known liver disease&#xD;
&#xD;
          -  Clinical history of cardiac pathology including known long QT syndrome&#xD;
&#xD;
          -  Unable to cooperate with the requirements of the study&#xD;
&#xD;
          -  Participating in other intervention studies&#xD;
&#xD;
          -  Delivery onset (characterized by painful uterine contractions and variable changes of&#xD;
             the cervix, including some degree of effacement and slower progression of dilatation&#xD;
             up to 5 cm for first and subsequent labours)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospital General de Segovia</name>
      <address>
        <city>Segovia</city>
        <state>Cartilla Y León</state>
        <zip>40002</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Sant Creu i Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sant Joan de Déu</name>
      <address>
        <city>Esplugues De Llobregat</city>
        <state>Catalunya</state>
        <zip>08950</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Fundación Alcorcón</name>
      <address>
        <city>Alcorcón</city>
        <state>Madrid</state>
        <zip>28922</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HM Puerta del Sur</name>
      <address>
        <city>Móstoles</city>
        <state>Madrid</state>
        <zip>28938</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Torrejón</name>
      <address>
        <city>Torrejón De Ardoz</city>
        <state>Madrid</state>
        <zip>28850</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Infanta Leonor</name>
      <address>
        <city>Madrid</city>
        <zip>28031</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>January 11, 2022</last_update_submitted>
  <last_update_submitted_qc>January 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pregnancy</keyword>
  <keyword>covid-19</keyword>
  <keyword>coronavirus</keyword>
  <keyword>hydroxychloroquine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</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>Yes</sharing_ipd>
    <ipd_description>It would be shared at time of publication.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>By the end of study</ipd_time_frame>
  </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/NCT04410562
org study id: 2020-001587-29
nct id: NCT04410562
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
It still unclear how SARS-CoV-2 affects pregnant women and their offspring, as well as which
      factors may influence obstetrical disease and outcomes, including the timing of maternal
      viral exposure by gestational age, the effects of parity, age, host immune responses,
      coexisting medical and obstetrical conditions and the effects of treatment regimens. While
      further information is gathered, based on the existing evidence from other infections causing
      pneumonia, pregnant women should be considered to be at high risk for developing severe
      infection during the current COVID-19 epidemic. Results from clinical trials with HCQ in
      nonpregnant adults may not be directly extrapolated to pregnant women given the special
      features of the pregnancy status. Thus, clinical research is urgently needed to improve the
      care and reduce the risk of poor pregnancy outcomes of women in this and in future epidemics.
This is a randomized, double blinded, placebo-controlled multicenter clinical trial including
      714 pregnant women (200 SARS-CoV-2 infected -100 symptomatic with mild disease and 100
      asymptomatic- pregnant women and 514 SARS-CoV-2 uninfected pregnant women who are contacts
      with a SARS-CoV-2 case) with the main objectives of assessing the safety and efficacy of oral
      hydroxychloroquine (HCQ) in reducing maternal viral shedding by PCR, and preventing incident
      SARS-CoV-2 infection and disease severity. Pregnant women undergoing antenatal follow up at
      five maternity hospitals, presenting at least one sign and/or one mild suggestive symptoms
      and a positive SARS-CoV-2 PCR test, or who are contacts of a suspected or confirmed case,
      will be recruited and randomized 1:1 to receive HCQ orally (400 mg/day for 3 days, followed
      by 200 mg/day for 11 days) or placebo. Women will be followed up for the duration of the
      intervention. One week after intervention completion, a SARS-CoV-2 PCR test will be repeated.
      At delivery, the pregnancy outcome will be registered, and a cord blood sample will be
      collected to measure for IgG and IgM of SARS-CoV-2. A neonatal nasopharyngeal aspirate will
      be collected to perform PCR SARS-CoV-2 testing.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, double-blinded, placebo-controlled multicentre clinical trial.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of PCR confirmed cases among pregnant women
time frame: 21 days after intervention
description: Number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start
measure: Incidence of COVID-19 disease during pregnancy
time frame: through study completion, an average of 1 year
measure: Incidence of COVID-19-related admissions
time frame: through study completion, an average of 1 year
measure: Incidence of all-cause admissions
time frame: through study completion, an average of 1 year
measure: Incidence of all-cause outpatient attendances
time frame: through study completion, an average of 1 year
measure: Mean duration of symptoms-signs of COVID-19
time frame: through study completion, an average of 1 year
measure: Frequency and severity of adverse events
time frame: through study completion, an average of 1 year
measure: Incidence of preeclampsia
time frame: through study completion, an average of 1 year
measure: Incidence of gestational diabetes
time frame: through study completion, an average of 1 year
measure: Incidence of SARS-CoV-2 infections during pregnancy
time frame: through study completion, an average of 1 year
measure: Prevalence of intrauterine growth restriction
time frame: through study completion, an average of 1 year
measure: Maternal mortality rate
time frame: through study completion, an average of 1 year
measure: Proportion of neonates with SARS-CoV-2- intrauterine infection by PCR-confirmed SARS-CoV-2-infection in nasopharyngeal aspirate.
time frame: through study completion, an average of 1 year
measure: Proportion of neonates with clinical signs/symptoms of COVID-19
time frame: through study completion, an average of 1 year
measure: Prevalence of low birth weight (<10th centile according to local standards)
time frame: through study completion, an average of 1 year
measure: Prevalence of preterm birth (<37 weeks of gestational age)
time frame: through study completion, an average of 1 year
measure: Prevalence of embryo and foetal losses (miscarriages and stillbirths)
time frame: through study completion, an average of 1 year
measure: Frequency of congenital malformations
time frame: through study completion, an average of 1 year
measure: Proportion of adverse perinatal outcome
time frame: through study completion, an average of 1 year
measure: Neonatal morbidity
time frame: through study completion, an average of 1 year
measure: Neonatal mortality rate
time frame: through study completion, an average of 1 year
arm group label: Hydroxychloroquine
arm group type: Experimental
description: Participants will be then randomized in a 1:1 ratio to HCQ (400 mg/day for three days, followed by 200 mg/day for 11 days)
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will be then randomized in a 1:1 ratio to placebo (2 tablets for three days, followed by one tablet for 11 days).
intervention type: Drug
intervention name: Hydroxychloroquine
description: Participants will receive a bottle containing 19 tablets of study medication. They will be instructed to take two tablets for the first three days and one tablet for the following 11 days. (400 mg/day for three days, followed by 200 mg/day for 11 days).
arm group label: Hydroxychloroquine
other name: Dolquine
intervention type: Drug
intervention name: Placebo
description: Participants will receive a bottle containing 19 tablets of placebo. They will be instructed to take two tablets for the first three days and one tablet for the following 11 days.
arm group label: Placebo
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Hydroxychloroquine
sharing ipd: Yes
ipd description: It would be shared at time of publication.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: By the end of study