<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/NCT04420247</url>
  </required_header>
  <id_info>
    <org_study_id>CLOROTRIAL</org_study_id>
    <nct_id>NCT04420247</nct_id>
  </id_info>
  <brief_title>Efficacy of Chloroquine or Hydroxychloroquine in Treating Pneumonia Caused by SARS-Cov-2 - COVID-19</brief_title>
  <official_title>Multicentric Pragmatic Randomized Controled Trial to Evaluate the Efficacy Chloroquine or Hydroxychloroquine for Five Days in Treating Pneumonia Caused by SARS-Cov-2 - COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva</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>
      Facing the challenge of finding an efficient treatment for COVID-19, the viral pneumonia&#xD;
      caused by the Coronavirus SARS-Cov-2, this study intended to test if Chloroquine or&#xD;
      Hydroxychloroquine, two drugs with strong in-vitro antiviral role proven by numerous studies&#xD;
      and with a well defined safety profile established, for efficacy in treating COVID-19 and&#xD;
      improving an ordinal primary outcome composed by a 9-levels scale, which was recomended by&#xD;
      the World Health Organization.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 3, Pragmatic, Multicentric Randomized Controled Trial of efficacy to test the&#xD;
      effect of either Chloroquine or Hydroxychloroquine for 5 days in the recomended dose&#xD;
      standardized by brazilian Ministry of Health.&#xD;
&#xD;
      Patients were randomized (1:1) using stratified randomization by hospital and severity at the&#xD;
      moment of randomization (stipulated by use of mechanical ventilation or not) into two arms:&#xD;
      Intervention and Control. Intervention group recieved a loading dose of 900mg of Chloroquine&#xD;
      or 800mg of Hydroxycloroquine in the first day, followed by 450mg of chloroquine of 400mg of&#xD;
      hydroxychloroquine. Primary and secondary outcomes were evaluated on the 5th, 7th, 10th,&#xD;
      14th, 28th day after randomization.&#xD;
&#xD;
      Although the outcomes presented in the latest version were updated late on&#xD;
      ClinicalTrials.org, on October 23, 2020, these outcomes were already present in the trial&#xD;
      protocol approved by the Brazilian National Commission for Ethics in Research on April 8,&#xD;
      2020 (approval number: 3960331) and amending the protocol, approved by the same National&#xD;
      Commission on May 25, 2020 (approval number: 4044848)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 16, 2020</start_date>
  <completion_date type="Actual">September 3, 2020</completion_date>
  <primary_completion_date type="Actual">August 20, 2020</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>Two arms - Intervention and Control Intervention received unblinded treatment with Chloroquine or Hyroxycloroquine for 5 days, as well as standard treatment available and recomended by the Brazilian Guidelines for COVID-19.&#xD;
Control group received just the standard treatment available and recomended by the Brazilian Guidelines for COVID-19.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>World Health Organization (WHO) 9-levels ordinal scale (from 0-8)</measure>
    <time_frame>14 days after randomization</time_frame>
    <description>Evaluation of the clinical status of patients on the 14th day after randomization defined by the 9-levels ordinal scale, with lower scores meaning better outcomes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>World Health Organization (WHO) 9-levels ordinal scale (from 0-8)</measure>
    <time_frame>5, 7, 10 and 28 days after randomization</time_frame>
    <description>Evaluation of the clinical status of patients on the 5th, 7th, 10th and 28th day after randomization defined by the 9-levels ordinal scale, with lower scores meaning better outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>28 days after randomization</time_frame>
    <description>All-cause mortality at 28 days after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilation free days</measure>
    <time_frame>28 days after randomization</time_frame>
    <description>Number of days without need of Mechanical Ventilation at 28 days after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU Lenght of Stay</measure>
    <time_frame>28 days after randomization</time_frame>
    <description>ICU Lenght of Stay on survivors at 28 days after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Lenght of Stay</measure>
    <time_frame>28 days after randomization</time_frame>
    <description>Hospital Lenght of Stay on survivors at 28 days after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Kidney Disease incidence</measure>
    <time_frame>28 days after randomization</time_frame>
    <description>Acute Kidney Disease incidence measured by Kidney Disease Improving Global Outcomes (KDIGO) stage 3 sometime until the 28th day after randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients needing dialysis</measure>
    <time_frame>28 days after randomization</time_frame>
    <description>Percentage of patients needing dialysis sometime until the 28th day.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulopathy incidence</measure>
    <time_frame>28 days after randomization</time_frame>
    <description>Presence of coagulopathy sometime until the 28th day (platelets &lt; 150000 and/or INR &gt;1.5 and/or KPTT &gt; 35 seconds).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean of C Reactive Protein Levels</measure>
    <time_frame>5, 7, 10, 14 and 28 days after randomization</time_frame>
    <description>Mean of C Reactive Protein Levels on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sequential Organ Failure Assessment (SOFA) scores</measure>
    <time_frame>5, 7, 10, 14 and 28 days after randomization</time_frame>
    <description>Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neutrophils/lymphocytes ratio</measure>
    <time_frame>5, 7, 10, 14 and 28 days after randomization</time_frame>
    <description>Neutrophils/lymphocytes ratio on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Arrhythmia</measure>
    <time_frame>28 days after randomization</time_frame>
    <description>Safety outcome: Any kind of arrhythmia identified by the attending physician at the time of the intercurrence, confirmed by an electrocardiogram (ECG), sometime until the 28th day</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">142</enrollment>
  <condition>COVID</condition>
  <condition>COVID-19</condition>
  <condition>SARS-CoV 2</condition>
  <condition>Coronavirus</condition>
  <condition>Corona Virus Infection</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment with either Chloroquine or Hydroxychloroquine according to what was available in the hospital:&#xD;
Chloroquine - 900mg on the first day, followed by 450mg in the next 4 days. Hydroxychloroquine - 800mg on the first day, followed by 450mg in the next 4 days.&#xD;
+&#xD;
Standard treatment available and recomended by the Brazilian Guidelines for COVID-19.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard treatment available and recomended by the Brazilian Guidelines for COVID-19.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chloroquine</intervention_name>
    <description>5 days of treatment with Chloroquine + Standard Care</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine</intervention_name>
    <description>5 days of treatment with Hydroxychloroquine + Standard Care</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>standard care</intervention_name>
    <description>Standard Care according to Brazilian Guidelines for treating COVID-19</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult Males and non-pregnant females that accept and sign the informed consent.&#xD;
&#xD;
          -  Hospitalized with COVID-19 suspection that has collected the confirmatory test&#xD;
&#xD;
          -  To have at least one of thes symptoms: Fever, coughing, throat ache or runny nose.&#xD;
&#xD;
          -  To have at least one of these findings: radiological findings that indicates COVID-10&#xD;
             (bilatareal ground grass images); O2 saturation lower than 94% without supplementation&#xD;
             and crackles in lung auscultation; Need of O2 supplementation; Need of Mechanical&#xD;
             Ventilation.&#xD;
&#xD;
          -  Female patients must also agree to use efficient counterceptive methods during the&#xD;
             evaluation period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with psoriasis or other exfoliative disease, porphyria, epilepsy, myasthenia&#xD;
             gravis, advanced liver failure or glucose-6-phosphate dehydrogenase deficiency.&#xD;
&#xD;
          -  ALT / AST&gt; 5 times the upper limit of normal.&#xD;
&#xD;
          -  Severe chronic kidney disease in stage 4 or requiring dialysis (ie, eGFR &lt;30).&#xD;
&#xD;
          -  Pregnancy or breastfeeding.&#xD;
&#xD;
          -  Early transfer to another hospital that is not a study site within 72 hours.&#xD;
&#xD;
          -  Severe heart disease and / or a history of cardiac arrhythmia.&#xD;
&#xD;
          -  Allergy to Chloroquine and / or Hydroxychloroquine.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Centro de Estudos e Pesquisa em Emergencias Clinicas e Terapia Intensiva</name>
      <address>
        <city>Curitiba</city>
        <state>Parana</state>
        <zip>82530200</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>May 10, 2021</last_update_submitted>
  <last_update_submitted_qc>May 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva</investigator_affiliation>
    <investigator_full_name>ALVARO REA-NETO, MD</investigator_full_name>
    <investigator_title>Director of the Reseach Center</investigator_title>
  </responsible_party>
  <keyword>VIRAL PNEUMONIA</keyword>
  <keyword>CORONAVIRUS</keyword>
  <keyword>COVID-19</keyword>
  <keyword>COVID</keyword>
  <keyword>SARS-COV-2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</mesh_term>
    <mesh_term>Chloroquine</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/NCT04420247
org study id: CLOROTRIAL
nct id: NCT04420247
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Facing the challenge of finding an efficient treatment for COVID-19, the viral pneumonia
      caused by the Coronavirus SARS-Cov-2, this study intended to test if Chloroquine or
      Hydroxychloroquine, two drugs with strong in-vitro antiviral role proven by numerous studies
      and with a well defined safety profile established, for efficacy in treating COVID-19 and
      improving an ordinal primary outcome composed by a 9-levels scale, which was recomended by
      the World Health Organization.
This is a Phase 3, Pragmatic, Multicentric Randomized Controled Trial of efficacy to test the
      effect of either Chloroquine or Hydroxychloroquine for 5 days in the recomended dose
      standardized by brazilian Ministry of Health.

      Patients were randomized (1:1) using stratified randomization by hospital and severity at the
      moment of randomization (stipulated by use of mechanical ventilation or not) into two arms:
      Intervention and Control. Intervention group recieved a loading dose of 900mg of Chloroquine
      or 800mg of Hydroxycloroquine in the first day, followed by 450mg of chloroquine of 400mg of
      hydroxychloroquine. Primary and secondary outcomes were evaluated on the 5th, 7th, 10th,
      14th, 28th day after randomization.

      Although the outcomes presented in the latest version were updated late on
      ClinicalTrials.org, on October 23, 2020, these outcomes were already present in the trial
      protocol approved by the Brazilian National Commission for Ethics in Research on April 8,
      2020 (approval number: 3960331) and amending the protocol, approved by the same National
      Commission on May 25, 2020 (approval number: 4044848)
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Two arms - Intervention and Control Intervention received unblinded treatment with Chloroquine or Hyroxycloroquine for 5 days, as well as standard treatment available and recomended by the Brazilian Guidelines for COVID-19.
Control group received just the standard treatment available and recomended by the Brazilian Guidelines for COVID-19.
primary purpose: Treatment
masking: None (Open Label)
measure: World Health Organization (WHO) 9-levels ordinal scale (from 0-8)
time frame: 14 days after randomization
description: Evaluation of the clinical status of patients on the 14th day after randomization defined by the 9-levels ordinal scale, with lower scores meaning better outcomes.
measure: World Health Organization (WHO) 9-levels ordinal scale (from 0-8)
time frame: 5, 7, 10 and 28 days after randomization
description: Evaluation of the clinical status of patients on the 5th, 7th, 10th and 28th day after randomization defined by the 9-levels ordinal scale, with lower scores meaning better outcomes.
measure: Mortality
time frame: 28 days after randomization
description: All-cause mortality at 28 days after randomization
measure: Ventilation free days
time frame: 28 days after randomization
description: Number of days without need of Mechanical Ventilation at 28 days after randomization
measure: ICU Lenght of Stay
time frame: 28 days after randomization
description: ICU Lenght of Stay on survivors at 28 days after randomization
measure: Hospital Lenght of Stay
time frame: 28 days after randomization
description: Hospital Lenght of Stay on survivors at 28 days after randomization
measure: Acute Kidney Disease incidence
time frame: 28 days after randomization
description: Acute Kidney Disease incidence measured by Kidney Disease Improving Global Outcomes (KDIGO) stage 3 sometime until the 28th day after randomization.
measure: Percentage of patients needing dialysis
time frame: 28 days after randomization
description: Percentage of patients needing dialysis sometime until the 28th day.
measure: Coagulopathy incidence
time frame: 28 days after randomization
description: Presence of coagulopathy sometime until the 28th day (platelets < 150000 and/or INR >1.5 and/or KPTT > 35 seconds).
measure: Mean of C Reactive Protein Levels
time frame: 5, 7, 10, 14 and 28 days after randomization
description: Mean of C Reactive Protein Levels on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization
measure: Sequential Organ Failure Assessment (SOFA) scores
time frame: 5, 7, 10, 14 and 28 days after randomization
description: Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.
measure: Neutrophils/lymphocytes ratio
time frame: 5, 7, 10, 14 and 28 days after randomization
description: Neutrophils/lymphocytes ratio on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.
measure: Arrhythmia
time frame: 28 days after randomization
description: Safety outcome: Any kind of arrhythmia identified by the attending physician at the time of the intercurrence, confirmed by an electrocardiogram (ECG), sometime until the 28th day
arm group label: Intervention
arm group type: Experimental
description: Treatment with either Chloroquine or Hydroxychloroquine according to what was available in the hospital:
Chloroquine - 900mg on the first day, followed by 450mg in the next 4 days. Hydroxychloroquine - 800mg on the first day, followed by 450mg in the next 4 days.
+
Standard treatment available and recomended by the Brazilian Guidelines for COVID-19.
arm group label: Control
arm group type: Active Comparator
description: Standard treatment available and recomended by the Brazilian Guidelines for COVID-19.
intervention type: Drug
intervention name: Chloroquine
description: 5 days of treatment with Chloroquine + Standard Care
arm group label: Intervention
intervention type: Drug
intervention name: Hydroxychloroquine
description: 5 days of treatment with Hydroxychloroquine + Standard Care
arm group label: Intervention
intervention type: Other
intervention name: standard care
description: Standard Care according to Brazilian Guidelines for treating COVID-19
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva
investigator full name: ALVARO REA-NETO, MD
investigator title: Director of the Reseach Center
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Coronavirus Infections
mesh term: Hydroxychloroquine
mesh term: Chloroquine
sharing ipd: No