<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/NCT04466540</url>
  </required_header>
  <id_info>
    <org_study_id>30415320.8.1001.0070</org_study_id>
    <nct_id>NCT04466540</nct_id>
  </id_info>
  <brief_title>Randomized Placebo-controlled Trial of Hydroxychloroquine in Outpatient Cases With Coronavirus Disease 2019 (COVID-19)</brief_title>
  <acronym>COALITION-V</acronym>
  <official_title>Pragmatic, Double-blind, Placebo-controlled Randomized Clinical Trial, Evaluating Hydroxychloroquine for Prevention of Hospitalization and Respiratory Complications in Non-hospitalized Patients With Confirmed or Probable COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Alemão Oswaldo Cruz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>EMS S/A</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital do Coracao</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Israelita Albert Einstein</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Sirio-Libanes</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Moinhos de Vento</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Brazilian Research In Intensive Care Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital Alemão Oswaldo Cruz</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>
      In December 2019, a group of patients with pneumonia of unknown cause was identified in&#xD;
      Wuhan, in the Hubei province, China. Despite the need of target specific therapeutic options&#xD;
      for COVID-19, until now there is no proof of effectiveness of any specific intervention. Some&#xD;
      limited observational trials and also evidence from randomized trials have shown no benefit&#xD;
      of hydroxychloroquine in inpatient context. Thus, studies evaluating interventions in an&#xD;
      outpatient setting in non-severe patients can provide important information related to&#xD;
      prognosis and safety. In this way, the present study will evaluate the effectiveness and&#xD;
      safety of the use of hydroxychloroquine in COVID-19 outpatients by means of a Randomized,&#xD;
      double-blind, placebo-controlled trial&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pragmatic, double-blind, placebo-controlled randomized parallel-group, two-arm clinical trial&#xD;
      (with allocation ratio 1:1), evaluating hydroxychloroquine (800 mg at 1st day, and 400 mg&#xD;
      from day 2 to 7) for prevention of hospitalization and respiratory complications in&#xD;
      non-hospitalized confirmed or suspected COVID-19 cases. Key inclusion criteria are adults&#xD;
      (equal to or greater tahn 18 years) seeking medical care with suspected or confirmed&#xD;
      COVID-19, with time between symptoms and inclusion ≤ 07 days, presenting mild symptoms,&#xD;
      without indication of hospitalization and at least one risk factor for complication (&gt; 65&#xD;
      years; hypertension; diabetes mellitus; asthma; Chronic Obstructive Pulmonary Disease (COPD)&#xD;
      or other chronic lung diseases; smoking; immunosuppression; obesity (Defined as BMI equal to&#xD;
      or greater than 30 Kg/m2). Primary endpoint is to assess if the treatment with&#xD;
      hydroxychloroquine is able to avoid hospitalization due to a COVID-19-related clinical reason&#xD;
      within 30 days of randomization in an outpatient setting. Hospitalization is considered to be&#xD;
      hospital stay for a period &gt; 24h or an additional hospitalized calendar day. The primary&#xD;
      endpoint is centrally adjudicated by an independent clinical events committee blinded to the&#xD;
      assigned treatment groups. Secondary endpoints include uncontrolled asthma after ≥ 5 days of&#xD;
      starting study medication; pneumonia; otitis media; fever resolution time; time to improve&#xD;
      respiratory symptoms; hospitalization in the Intensive Care Unit; need for orotracheal&#xD;
      intubation; mechanical ventilation time; mortality. Safety outcomes will be hypoglycemia;&#xD;
      palpitations; reduced visual acuity; diarrhea; anorexia; and emotional lability. The&#xD;
      evaluation of the primary outcome (hospitalization within 30 days) will be performed for the&#xD;
      included population following the principle of intention-to-treat (ITT), which will consist&#xD;
      of all randomized cases. A modified intention-to-treat analysis (mITT), in which cases&#xD;
      definitely confirmed as negative for COVID-19 will be excluded, will also be performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 12, 2020</start_date>
  <completion_date type="Actual">September 28, 2021</completion_date>
  <primary_completion_date type="Actual">July 28, 2021</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>
    <intervention_model_description>Pragmatic, double-blind, placebo-controlled randomized parallel-group, two-arm clinical trial (with allocation ratio 1:1)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Randomization (1:1) is generated by a validated software and performed in permuted blocks of size 8. Concealment of the randomization list is maintained through a 24-hour, centralized, automated, internet-based randomization system. Furthermore, as placebo-controlled study, the placebo will have the same structural characteristics as the active drug and will be dispensed in cartridges that do not allow the identification of what is being given</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Hospitalization</measure>
    <time_frame>30 days from randomization</time_frame>
    <description>To assess if the treatment is able to avoid hospitalization due to a COVID-19-related clinical reason within 30 days of randomization in an outpatient setting. Hospitalization is considered to be hospital stay for a period &gt; 24h or an additional hospitalized calendar day.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Uncontrolled asthma after ≥ 5 days of starting study medication</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Affirmative answer in three or four items of the Global Initiative for Asthma (GINA) questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pneumonia</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Defined by clinical-radiological criteria - a history of cough and one or more of the following symptoms: sputum, dyspnea, chest pain, sweating or fever (T&gt; 37.8o C) + Chest CT scan showing ground-glass opacity, focal consolidations or mixed opacities (including reverse halo sign), uni or bilateral</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Otitis media</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Defined by clinical criteria - Fever (T&gt; 37.8o C) and otalgia + bulging of the tympanic membrane</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fever resolution time</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Day 0 of fever resolution will be defined as the first afebrile day (T &lt;37.5o C) after inclusion in the study followed by at least two consecutive days. The temperature will be obtained through the participant report in the patient's diary</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to improve respiratory symptoms</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Time to improve respiratory symptoms (cough, runny nose)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalization in the Intensive Care Unit</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Admission to ICU due to clinical reasons related to COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for Orotracheal Intubation</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Clinical need for Orotracheal Intubation as assessed by the physician responsible for the case</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanical Ventilation Time</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Number of days on mechanical ventilation until extubation or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Death due to any cause that occurred within 30 days after inclusion in the study</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Hypoglycemia</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Change in the frequency of hypoglycemic episodes in diabetic patients using hypoglycemic medication, perceived by clinical signs or symptoms or measured in a capillary or blood glucose device</description>
  </other_outcome>
  <other_outcome>
    <measure>Palpitations</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Presence of cardiac arrhythmias in patients without known history of prolongation of the measure between Q wave and T wave in the heart's electrical cycle (QTc) or pre-existing heart disease;</description>
  </other_outcome>
  <other_outcome>
    <measure>Reduced visual acuity</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Change in visual acuity or new diagnosis of retinal disease not previously documented</description>
  </other_outcome>
  <other_outcome>
    <measure>Diarrhea</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Change in bowel habit greater than three (3) diarrheal episodes per day during the use of hydroxychloroquine medication and 3 days after its end</description>
  </other_outcome>
  <other_outcome>
    <measure>Anorexia</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Change in appetite during medication use hydroxychloroquine and 3 days after the end of treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>Emotional lability</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Perception of change in emotional lability (mood swings) during hydroxychloroquine use and 3 days after the end of treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to hospitalization after randomization</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Time from randomization to hospitalization</description>
  </other_outcome>
  <other_outcome>
    <measure>Assessment of the patient clinical status at the time of hospitalization</measure>
    <time_frame>within 30 days from randomization</time_frame>
    <description>Clinical and vital signs assessed when admitted to hospital</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1372</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Hydroxychloroquine (HCQ)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HCQ group participants will receive a dose of 400mg twice daily (BID) in the first day, and a dose of 400 mg once daily (OD) from the second day of treatment, in a total of 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo group will follow the same regimen of administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine</intervention_name>
    <description>Hydroxychloroquine pharmaceutical form will be tablets of 400 mg.</description>
    <arm_group_label>Hydroxychloroquine (HCQ)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Hydroxychloroquine placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        It will be considered eligible those adults (equal to or greater than 18 years) seeking&#xD;
        medical care with suspected or confirmed COVID-19, with time between symptoms and inclusion&#xD;
        ≤ 07 days, presenting mild symptoms, without indication of hospitalization and at least 1&#xD;
        risk factor for complication:&#xD;
&#xD;
          1. &gt; 65 years;&#xD;
&#xD;
          2. Hypertension;&#xD;
&#xD;
          3. Diabetes mellitus;&#xD;
&#xD;
          4. Asthma;&#xD;
&#xD;
          5. COPD or other chronic lung diseases;&#xD;
&#xD;
          6. Smoking;&#xD;
&#xD;
          7. Immunosuppression;&#xD;
&#xD;
          8. Obesity (Defined as BMI equal to or greater than 30 Kg/m2).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients under 18 years old;&#xD;
&#xD;
          2. Hospitalization at the first medical care;&#xD;
&#xD;
          3. Positive test for influenza at the first medical care;&#xD;
&#xD;
          4. Known hypersensitivity to hydroxychloroquine / chloroquine;&#xD;
&#xD;
          5. Previous diagnosis of retinopathy or macular degeneration;&#xD;
&#xD;
          6. Previous diagnosis of Long QT-syndrome, history of sudden death in close family&#xD;
             members (parents and siblings), decompensated heart failure, unstable coronary artery&#xD;
             disease, use of anti-arrhythmic drugs or other drugs that can increase the&#xD;
             hydroxychloroquine bioavailability or enhance its effect;&#xD;
&#xD;
          7. Evidence of known liver disease, reported by the patient;&#xD;
&#xD;
          8. Evidence of known chronic kidney disease, reported by the patient;&#xD;
&#xD;
          9. Patients with pancreatitis;&#xD;
&#xD;
         10. Baseline ECG with QTc interval ≥ 480ms;&#xD;
&#xD;
         11. Chronic use of hydroxychloroquine/chloroquine for other reasons;&#xD;
&#xD;
         12. Pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Álvaro Avezum, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>International Research Center - Hospital Alemão Oswaldo Cruz</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centro de Pesquisas Clínicas Dr. Marco Mota HCOR</name>
      <address>
        <city>Maceió</city>
        <state>Alagoas</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital e Clínica São Roque</name>
      <address>
        <city>Ipiaú</city>
        <state>Bahia</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica Otorhinus</name>
      <address>
        <city>Salvador</city>
        <state>Bahia</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital da Bahia</name>
      <address>
        <city>Salvador</city>
        <state>Bahia</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Izabel</name>
      <address>
        <city>Salvador</city>
        <state>Bahia</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Cárdio Pulmonar da Bahia</name>
      <address>
        <city>Salvador</city>
        <state>Bahia</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital SAMUR</name>
      <address>
        <city>Vitória Da Conquista</city>
        <state>Bahia</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Maternidade São Vicente de Paulo</name>
      <address>
        <city>Barbalha</city>
        <state>Ceará</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Unimed Cariri</name>
      <address>
        <city>Juazeiro Do Norte</city>
        <state>Ceará</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unimed Sul Capixaba</name>
      <address>
        <city>Cachoeiro De Itapemirim</city>
        <state>Espírito Santo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital das Clínicas Universidade Federal de Goiás</name>
      <address>
        <city>Goiânia</city>
        <state>Goiás</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santa Casa de Misericórdia de Passos</name>
      <address>
        <city>Passos</city>
        <state>Minas Agerais</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Júlia Kubitschek</name>
      <address>
        <city>Belo Horizonte</city>
        <state>Minas Gerais</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto da Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa</name>
      <address>
        <city>Belo Horizonte</city>
        <state>Minas Gerais</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Casa de Caridade de Carangola</name>
      <address>
        <city>Carangola</city>
        <state>Minas Gerais</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Maternidade e Pronto Socorro Santa Lucia</name>
      <address>
        <city>Poços De Caldas</city>
        <state>Minas Gerais</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital da Unimed</name>
      <address>
        <city>São João Del Rei</city>
        <state>Minas Gerais</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santa Casa de Misericórdia de São João Del Rei</name>
      <address>
        <city>São João Del Rei</city>
        <state>Minas Gerais</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Clínicas da Universidade Federal do Triangulo Mineiro</name>
      <address>
        <city>Uberaba</city>
        <state>Minas Gerais</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Clínicas da Universidade Federal de Uberlândia</name>
      <address>
        <city>Uberlândia</city>
        <state>Minas Gerais</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital do Rocio</name>
      <address>
        <city>Campo Largo</city>
        <state>Paraná</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica Clinilive</name>
      <address>
        <city>Maringá</city>
        <state>Paraná</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitário Regional de Maringá</name>
      <address>
        <city>Maringá</city>
        <state>Paraná</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PROCAPE</name>
      <address>
        <city>Recife</city>
        <state>Pernambuco</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Real Hospital Português de Beneficência em Pernambuco</name>
      <address>
        <city>Recife</city>
        <state>Pernambuco</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SECRETARIA MUNICIPAL DE SAÚDE DE SAIRÉ (Unidade Mista Olília Mendonça Souto Maior)</name>
      <address>
        <city>Sairé</city>
        <state>Pernambuco</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complexo Hospitalar de Niterói</name>
      <address>
        <city>Niterói</city>
        <state>Rio De Janeiro</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Unimed Volta Redonda</name>
      <address>
        <city>Volta Redonda</city>
        <state>Rio De Janeiro</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Associação Dr. Bartholomeu Tacchini</name>
      <address>
        <city>Bento Gonçalves</city>
        <state>Rio Grande Do Sul</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital São Vicente de Paulo</name>
      <address>
        <city>Passo Fundo</city>
        <state>Rio Grande Do Sul</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Moinhos de Vento</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santa Casa de Misericórdia de Porto Alegre (ISCMPA)</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universidade Federal de Santa Maria</name>
      <address>
        <city>Santa Maria</city>
        <state>Rio Grande Do Sul</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CEPEM Centro de Pesquisa de Medicina Tropical de Rondônia</name>
      <address>
        <city>Porto Velho</city>
        <state>Rondônia</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irmandade de Misericórdia Do Hospital Da Santa Casa de Monte Alto</name>
      <address>
        <city>Monte alto</city>
        <state>Salto Alto</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maestri e Kormann Consultoria Medico Cientifica</name>
      <address>
        <city>Blumenau</city>
        <state>Santa Catarina</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imigrantes Hospital e Maternidade</name>
      <address>
        <city>Brusque</city>
        <state>Santa Catarina</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital São José</name>
      <address>
        <city>Criciúma</city>
        <state>Santa Catarina</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Regional Hans Dieter Schmidt</name>
      <address>
        <city>Joinville</city>
        <state>Santa Catarina</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santa Casa de Araras</name>
      <address>
        <city>Araras</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Amor</name>
      <address>
        <city>Barretos</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santa Casa de Misericórdia de Barretos</name>
      <address>
        <city>Barretos</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alphacor Cardiologia Clinica E Diagnóstica LTDA</name>
      <address>
        <city>Barueri</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Faculdade de Medicina de Botucatu, UNESP</name>
      <address>
        <city>Botucatu</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Regional do Litoral Norte</name>
      <address>
        <city>Caraguatatuba</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Cordeirópolis</name>
      <address>
        <city>Cordeirópolis</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Combate ao Coronavírus de Itapevi</name>
      <address>
        <city>Itapevi</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dux Medicina</name>
      <address>
        <city>Jundiaí</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Carlos Fenando Malzoni</name>
      <address>
        <city>Matão</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Atendimento Para O Enfrentamento A Covid-19 Da Prefeitura Municipal de Monte Altoprefeitura de Monte Alto</name>
      <address>
        <city>Monte alto</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Faculdade de Medicina de Ribeirão Preto</name>
      <address>
        <city>Ribeirão Preto</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unimed Ribeirão Preto</name>
      <address>
        <city>Ribeirão Preto</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Casa de Saúde de Santos</name>
      <address>
        <city>Santos</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Clínica e Hospital Dia</name>
      <address>
        <city>São José Do Rio Preto</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Policlin</name>
      <address>
        <city>São José Dos Campos</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Regional de São José dos Campos</name>
      <address>
        <city>São José Dos Campos</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santa Casa de Misericórdia de Votuporanga</name>
      <address>
        <city>Votuporanga</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ESF Dr. João Paccola Primo</name>
      <address>
        <city>Lençois Paulista</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardioclinica da Ilha do Governador</name>
      <address>
        <city>Rio De Janeiro</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>International Research Center - Hospital Alemão Oswaldo Cruz</name>
      <address>
        <city>São Paulo</city>
        <zip>01323-903</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital do Coração</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Israelita Albert Einstein</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Leforte</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Moriah</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Samaritano</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Paula</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital São Camilo Pompéia</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital São Paulo - UNIFESP</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sírio-Libanês</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>March 4, 2022</last_update_submitted>
  <last_update_submitted_qc>March 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Alemão Oswaldo Cruz</investigator_affiliation>
    <investigator_full_name>Álvaro Avezum Junior</investigator_full_name>
    <investigator_title>Research Manager - International Research Center</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Severe Acute Respiratory Syndrome - Coronavirus-2</keyword>
  <keyword>Hydroxychloroquine</keyword>
  <keyword>COALITION Brazil V 2019</keyword>
  <keyword>Outpatients</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>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/NCT04466540
org study id: 30415320.8.1001.0070
nct id: NCT04466540
lead sponsor: 
collaborator: 
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collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In December 2019, a group of patients with pneumonia of unknown cause was identified in
      Wuhan, in the Hubei province, China. Despite the need of target specific therapeutic options
      for COVID-19, until now there is no proof of effectiveness of any specific intervention. Some
      limited observational trials and also evidence from randomized trials have shown no benefit
      of hydroxychloroquine in inpatient context. Thus, studies evaluating interventions in an
      outpatient setting in non-severe patients can provide important information related to
      prognosis and safety. In this way, the present study will evaluate the effectiveness and
      safety of the use of hydroxychloroquine in COVID-19 outpatients by means of a Randomized,
      double-blind, placebo-controlled trial
Pragmatic, double-blind, placebo-controlled randomized parallel-group, two-arm clinical trial
      (with allocation ratio 1:1), evaluating hydroxychloroquine (800 mg at 1st day, and 400 mg
      from day 2 to 7) for prevention of hospitalization and respiratory complications in
      non-hospitalized confirmed or suspected COVID-19 cases. Key inclusion criteria are adults
      (equal to or greater tahn 18 years) seeking medical care with suspected or confirmed
      COVID-19, with time between symptoms and inclusion ≤ 07 days, presenting mild symptoms,
      without indication of hospitalization and at least one risk factor for complication (> 65
      years; hypertension; diabetes mellitus; asthma; Chronic Obstructive Pulmonary Disease (COPD)
      or other chronic lung diseases; smoking; immunosuppression; obesity (Defined as BMI equal to
      or greater than 30 Kg/m2). Primary endpoint is to assess if the treatment with
      hydroxychloroquine is able to avoid hospitalization due to a COVID-19-related clinical reason
      within 30 days of randomization in an outpatient setting. Hospitalization is considered to be
      hospital stay for a period > 24h or an additional hospitalized calendar day. The primary
      endpoint is centrally adjudicated by an independent clinical events committee blinded to the
      assigned treatment groups. Secondary endpoints include uncontrolled asthma after ≥ 5 days of
      starting study medication; pneumonia; otitis media; fever resolution time; time to improve
      respiratory symptoms; hospitalization in the Intensive Care Unit; need for orotracheal
      intubation; mechanical ventilation time; mortality. Safety outcomes will be hypoglycemia;
      palpitations; reduced visual acuity; diarrhea; anorexia; and emotional lability. The
      evaluation of the primary outcome (hospitalization within 30 days) will be performed for the
      included population following the principle of intention-to-treat (ITT), which will consist
      of all randomized cases. A modified intention-to-treat analysis (mITT), in which cases
      definitely confirmed as negative for COVID-19 will be excluded, will also be performed.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Pragmatic, double-blind, placebo-controlled randomized parallel-group, two-arm clinical trial (with allocation ratio 1:1)
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Randomization (1:1) is generated by a validated software and performed in permuted blocks of size 8. Concealment of the randomization list is maintained through a 24-hour, centralized, automated, internet-based randomization system. Furthermore, as placebo-controlled study, the placebo will have the same structural characteristics as the active drug and will be dispensed in cartridges that do not allow the identification of what is being given
measure: Hospitalization
time frame: 30 days from randomization
description: To assess if the treatment is able to avoid hospitalization due to a COVID-19-related clinical reason within 30 days of randomization in an outpatient setting. Hospitalization is considered to be hospital stay for a period > 24h or an additional hospitalized calendar day.
measure: Uncontrolled asthma after ≥ 5 days of starting study medication
time frame: within 30 days from randomization
description: Affirmative answer in three or four items of the Global Initiative for Asthma (GINA) questionnaire
measure: Pneumonia
time frame: within 30 days from randomization
description: Defined by clinical-radiological criteria - a history of cough and one or more of the following symptoms: sputum, dyspnea, chest pain, sweating or fever (T> 37.8o C) + Chest CT scan showing ground-glass opacity, focal consolidations or mixed opacities (including reverse halo sign), uni or bilateral
measure: Otitis media
time frame: within 30 days from randomization
description: Defined by clinical criteria - Fever (T> 37.8o C) and otalgia + bulging of the tympanic membrane
measure: Fever resolution time
time frame: within 30 days from randomization
description: Day 0 of fever resolution will be defined as the first afebrile day (T <37.5o C) after inclusion in the study followed by at least two consecutive days. The temperature will be obtained through the participant report in the patient's diary
measure: Time to improve respiratory symptoms
time frame: within 30 days from randomization
description: Time to improve respiratory symptoms (cough, runny nose)
measure: Hospitalization in the Intensive Care Unit
time frame: within 30 days from randomization
description: Admission to ICU due to clinical reasons related to COVID-19
measure: Need for Orotracheal Intubation
time frame: within 30 days from randomization
description: Clinical need for Orotracheal Intubation as assessed by the physician responsible for the case
measure: Mechanical Ventilation Time
time frame: within 30 days from randomization
description: Number of days on mechanical ventilation until extubation or death
measure: Mortality
time frame: within 30 days from randomization
description: Death due to any cause that occurred within 30 days after inclusion in the study
measure: Hypoglycemia
time frame: within 30 days from randomization
description: Change in the frequency of hypoglycemic episodes in diabetic patients using hypoglycemic medication, perceived by clinical signs or symptoms or measured in a capillary or blood glucose device
measure: Palpitations
time frame: within 30 days from randomization
description: Presence of cardiac arrhythmias in patients without known history of prolongation of the measure between Q wave and T wave in the heart's electrical cycle (QTc) or pre-existing heart disease;
measure: Reduced visual acuity
time frame: within 30 days from randomization
description: Change in visual acuity or new diagnosis of retinal disease not previously documented
measure: Diarrhea
time frame: within 30 days from randomization
description: Change in bowel habit greater than three (3) diarrheal episodes per day during the use of hydroxychloroquine medication and 3 days after its end
measure: Anorexia
time frame: within 30 days from randomization
description: Change in appetite during medication use hydroxychloroquine and 3 days after the end of treatment
measure: Emotional lability
time frame: within 30 days from randomization
description: Perception of change in emotional lability (mood swings) during hydroxychloroquine use and 3 days after the end of treatment
measure: Time to hospitalization after randomization
time frame: within 30 days from randomization
description: Time from randomization to hospitalization
measure: Assessment of the patient clinical status at the time of hospitalization
time frame: within 30 days from randomization
description: Clinical and vital signs assessed when admitted to hospital
arm group label: Hydroxychloroquine (HCQ)
arm group type: Experimental
description: HCQ group participants will receive a dose of 400mg twice daily (BID) in the first day, and a dose of 400 mg once daily (OD) from the second day of treatment, in a total of 7 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: The placebo group will follow the same regimen of administration
intervention type: Drug
intervention name: Hydroxychloroquine
description: Hydroxychloroquine pharmaceutical form will be tablets of 400 mg.
arm group label: Hydroxychloroquine (HCQ)
intervention type: Drug
intervention name: Placebo
description: Hydroxychloroquine placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Álvaro Avezum, Ph.D
role: Principal Investigator
affiliation: International Research Center - Hospital Alemão Oswaldo Cruz
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country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Hospital Alemão Oswaldo Cruz
investigator full name: Álvaro Avezum Junior
investigator title: Research Manager - International Research Center
mesh term: COVID-19
mesh term: Hydroxychloroquine
sharing ipd: No