<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/NCT04403100</url>
  </required_header>
  <id_info>
    <org_study_id>COVID19_AMB_Brasil</org_study_id>
    <nct_id>NCT04403100</nct_id>
  </id_info>
  <brief_title>Hydroxychloroquine and Lopinavir/ Ritonavir to Improve the Health of People With COVID-19: &quot;The Hope Coalition - 1&quot;</brief_title>
  <official_title>Hydroxychloroquine and Lopinavir/ Ritonavir for Hospitalization and Mortality Reduction in Patients With COVID-19 and Mild Disease Symptoms: &quot;The Hope Coalition&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cardresearch</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cardresearch - Cardiologia Assistencial e de Pesquisa LTDA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cytel Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Cardresearch</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>
      The COVID-19 pandemic has been characterized by high morbidity and mortality, especially in&#xD;
      certain subgroups of patients. To date, no treatment has been shown to be effective in&#xD;
      controlling this disease in hospitalized patients with moderate and / or severe cases of this&#xD;
      disease. Hydroxychloroquine and lopinavir / ritonavir have been shown to inhibit SARS-CoV&#xD;
      viral replication in experimental severe acute respiratory symptoms models and have similar&#xD;
      activity against SARS-CoV2. Although widely used in studies of critically ill patients, to&#xD;
      date, no study has demonstrated its role on the treatment of high-risk, newly diagnosed&#xD;
      patients with COVID-19 and mild symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In December 2019 a series of viral pneumonia cases were reported in the city of Wuhan, China.&#xD;
      A new subtype of coronavirus has been identified as the causative agent of this condition. On&#xD;
      February 11, 43,103 cases had already been described and on this day the World Health&#xD;
      Organization (WHO) named this disease as COVID-19. With. The disease had spread out to&#xD;
      several countries on different continents and on March 11, WHO declared a state of worldwide&#xD;
      pandemic. Today (April 25, 2020) there are 2,719,897 cases and 187,705 deaths documented,&#xD;
      with a global case-fatality ratio of 6.9%.&#xD;
&#xD;
      To date, no treatment has been identified as effective in combating this disease which has&#xD;
      been identified as with high mortality, therefore there are no specific therapeutic options.&#xD;
      So far, efforts have been focused on the treatment of patients hospitalized with dyspnea and,&#xD;
      although several promising drugs are being evaluated, none has demonstrated effectiveness in&#xD;
      reducing morbidity and mortality at this stage of the disease, suggesting that perhaps the&#xD;
      best time to use medications either before the onset of severe symptoms of respiratory&#xD;
      distress.&#xD;
&#xD;
      Thus, we propose the use of two drugs which experimentally have shown activity against&#xD;
      SARS-CoV2 and being used in severely ill patients with COVID-19. Our hypothesis is that&#xD;
      perhaps using such drugs before onset of complications will allow better outcomes on this&#xD;
      patient population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 3, 2020</start_date>
  <completion_date type="Anticipated">February 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">February 1, 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>Factorial Assignment</intervention_model>
    <intervention_model_description>Patients will be randomly allocated to one of four treatment arms in a 1:1:1:1 ratio:&#xD;
Lopinavir / Ritonavir&#xD;
Hydroxychloroquine&#xD;
Lopinavir / Ritonavir + Hydroxychloroquine&#xD;
Placebo.&#xD;
We will use a centralized random allocation schedule, generated by computer and implemented using an online remote access system. Randomization will be stratified by participating basic health unit.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The investigational medical product will be packaged in similar bottles by a third party who will keep the allocation confidential until the end of the study. The bottles will be sealed and identified as &quot;Research Product A, B and C&quot; and with different colored labels. They will be randomly allocated among the participants. The research subjects, medical assistance, administrative and health staff will not have access to the contents of the bottles. The Arm Lopinavir/ ritonavir plus hydroxychloroquine will receive two of such bottles.&#xD;
At the end of the study, after the statistical analysis and DMSB meeting, it will then be requested from third party documentation on content of each bottle and then have arms identified.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of participants who were hospitalized for progression of COVID-19 disease</measure>
    <time_frame>Measuring during 28-day period since randomization (Intention to treat analysis)</time_frame>
    <description>Hospitalization is defined as at least 24 hours of acute care in a hospital or similar acute care facility (emergency settings, temporary emergency facilities created for acute care of COVID-19 pandemic)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of participants who died due to COVID-19 progression and/ or complications</measure>
    <time_frame>Measuring during 28-day period since randomization (Intention to treat analysis)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with viral load change on 03, 07, 10 and 14 after randomization</measure>
    <time_frame>Measuring during 14-day period since randomization</time_frame>
    <description>Viral load change on 03, 07, 10 and 14 after randomization (200 patients per arm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to clinical improvement</measure>
    <time_frame>Measuring during 28-day period since randomization</time_frame>
    <description>Proportion of participants with clinical improvement, defined as normalization of temperature, Respiratory rate, SaO2, and cough relief (&gt; 50% compared to baseline measured on a visual analog scale) in the last 72 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to clinical failure</measure>
    <time_frame>Measuring during 28-day period since randomization</time_frame>
    <description>Proportion of participants with clinical improvement, defined as as time to need for hospitalization due to dyspnea, death, need for mechanical ventilation, shock and need for vasoactive amines;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalization for any cause</measure>
    <time_frame>Measuring during 28-day period since randomization</time_frame>
    <description>Proportion of participants with hospitalization for any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants who died due to pulmonary complications</measure>
    <time_frame>Measuring during 28-day period since randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants who died due to cardiovascular complications</measure>
    <time_frame>Measuring during 28-day period since randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants who presented with adverse events</measure>
    <time_frame>Measuring during 28-day period since randomization</time_frame>
    <description>Evaluation of adverse events evaluated as associated to any of study arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to improvement on respiratory scale symptoms</measure>
    <time_frame>Measuring during 28-day period since randomization</time_frame>
    <description>Proportion of participants who presented sustained improvement on respiratory scale defined as at least 48 hours of improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of non-adherent participants to any of study drugs</measure>
    <time_frame>Measuring during 10-day period since randomization</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">1968</enrollment>
  <condition>COVID-19</condition>
  <condition>Coronavirus Infection</condition>
  <condition>Virus Disease</condition>
  <condition>Acute Respiratory Infection</condition>
  <condition>SARS-CoV Infection</condition>
  <arm_group>
    <arm_group_label>Hydroxychloroquine Sulfate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Hydroxychloroquine 400 mg. Loading oral dose of 800 mg followed by orally dose of 400 mg/ day for the following 10 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lopinavir/ Ritonavir</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lopinavir Ritonavir 200/ 50 mg Loading oral dose of 800/ 200 mg twice a day on day 1 followed by 400/100 mg orally twice a day for the following 9 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hydroxychloroquine plus Lopinavir/ Ritonavir</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Hydroxychloroquine 400 mg. Loading oral dose of 800 mg followed by orally dose of 400 mg/ day for the following 10 days&#xD;
Plus&#xD;
Lopinavir Ritonavir 200/ 50 mg Loading oral dose of 800/ 200 mg twice a day on day 1 followed by 400/100 mg orally twice a day for the following 9 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo&#xD;
Twice a day from day 1 through day 10.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine Sulfate Tablets</intervention_name>
    <description>Tablets of 400 mg: Loading dose of 02 tablets followed by one tablet of 400 mg orally on the following 09 days</description>
    <arm_group_label>Hydroxychloroquine Sulfate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lopinavir/ Ritonavir Oral Tablet</intervention_name>
    <description>tablets of 200/ 50 mg; Loading dose of 04 tablets twice a day on day 1 followed by two tablets twice a day on the following 09 days</description>
    <arm_group_label>Lopinavir/ Ritonavir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets</intervention_name>
    <description>Hydroxychloroquine Oral Tablet 400 mg: Loading dose of 02 tablets followed by one tablet of 400 mg orally on the following 09 days&#xD;
plus&#xD;
Lopinavir/ Ritonavir Oral Tablet of 200/ 50 mg: Loading dose of 04 tablets twice a day on day 1 followed by two tablets twice a day on the following 09 days</description>
    <arm_group_label>Hydroxychloroquine plus Lopinavir/ Ritonavir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablets - 01 tablet twice daily from day 01 through day 10.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients with RT-PCR diagnosis of COVID-19 or a clinical condition compatible with COVID-19&#xD;
        and respiratory symptoms, presenting:&#xD;
&#xD;
        A. Persistent dry cough associated with axillary temperature &gt; 37.7 Celsius;&#xD;
&#xD;
        OR&#xD;
&#xD;
        B. Recent onset of Flu-like Respiratory Symptoms associated with dry cough&#xD;
&#xD;
        OR&#xD;
&#xD;
        C. Tomographic image compatible with COVID 19 infection;&#xD;
&#xD;
        2. Men and women aged &gt; 50 years OR: Patients over 18 years of age with at least one of the&#xD;
        following criteria&#xD;
&#xD;
          -  Diabetes requiring oral medication or insulin.&#xD;
&#xD;
          -  Arterial hypertension requiring at least 01 oral medication for treatment&#xD;
&#xD;
          -  Known cardiovascular diseases (CHF of any etiology, documented Coronary Artery&#xD;
             Disease, Clinically overt heart disease)&#xD;
&#xD;
          -  Symptomatic chronic lung disease and/ or medically controlled&#xD;
&#xD;
          -  Patients with a history of transplantation&#xD;
&#xD;
          -  Patient with stage IV chronic kidney disease or on dialysis.&#xD;
&#xD;
          -  Patients on current Immunosuppression and/or using corticosteroid therapy (equivalent&#xD;
             to at least 10 mg of oral prednisone per day)&#xD;
&#xD;
          -  Willingness to comply with study related procedures&#xD;
&#xD;
             3. Ability to provide informed consent before any protocol-related procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. RT-PCR exam for COVID-19 negative during the screening visit.&#xD;
&#xD;
          2. Patients with an acute respiratory condition compatible with COVID-19 being&#xD;
             hospitalized;&#xD;
&#xD;
          3. Patients with an acute respiratory condition and with moderate to high probability of&#xD;
             not being a COVID infection 19;&#xD;
&#xD;
          4. Dyspnea secondary to other acute and chronic respiratory causes or infections (eg,&#xD;
             decompensated Chronic Obstructive Pulmonary Disease, acute bronchitis, pneumonia,&#xD;
             primary pulmonary arterial hypertension);&#xD;
&#xD;
          5. Severe respiratory clinical condition, presenting at least ONE of the criteria below:&#xD;
&#xD;
               1. Respiratory Rate&gt; 28 / min;&#xD;
&#xD;
               2. Arterial Oxygen Saturation &lt; 92% with nasal oxygen therapy at 10 l/ min;&#xD;
&#xD;
               3. PaO2 / FIO2 &lt;300 mmHg&#xD;
&#xD;
        4. History of Cardiac Arrhythmia or Long QT Syndrome; 5. Use of Medications that are known&#xD;
        to prolong QTc: Citalopram, Venlafaxine, Bupropion and with no possibility of suspension&#xD;
        during the period of investigational medical product administration. 6. Inability to take&#xD;
        oral medications; 7. Patients on continuous use of Amiodarone and / or PGE5 Inhibitors (Ex&#xD;
        .: Sildenafil and similar). 8. Use of Digoxin, Cyclosporine, Cimetidine, Tamoxifen. 9. Use&#xD;
        of anticonvulsants, antifungals, immunosuppressants other than corticotherapy. 10. Use of&#xD;
        Hydroxychloroquine for other indications 11. Use of chemoprophylaxis for malaria. 12.&#xD;
        Psoriasis in a form other than cutaneous 13. Porphyria 14. Use of protease inhibitors,&#xD;
        ritonavir or Cobicistat 15. Clinical history of Liver Cirrhosis or Child-Pugh C&#xD;
        classification; 16. Patients with a history of degenerative retinal diseases (patients with&#xD;
        retinal diseases due to diabetes and hypertension can participate in the research); 17.&#xD;
        Patient with a clinically relevant history of hearing loss; 18. Patients with known severe&#xD;
        degenerative neurological diseases and / or severe mental illness; 19. Inability of the&#xD;
        patient or representative to give consent or adhere to the procedures proposed in the&#xD;
        protocol; 20. Known hypersensitivity and / or intolerance to Hydroxychloroquine. 21.&#xD;
        Hypersensitivity and / or intolerance Lopinavir / Ritonavir&#xD;
&#xD;
        -&#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>Gilmar Reis, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cardresearch - Cardiologia Assistencial e de Pesquisa LTDA</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gilmar Reis, MD, PhD</last_name>
    <phone>+5531332416574</phone>
    <email>greisbh@uol.com.br</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rosemary Oliveira, SC</last_name>
    <phone>+5531992636703</phone>
    <email>roliveira@cardresearch.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CARDRESEARCH - Cardiologia Assistencial e de Pesquisa</name>
      <address>
        <city>Belo Horizonte</city>
        <state>Minas Gerais</state>
        <zip>30150240</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Izabel Silva, SC</last_name>
      <phone>553132416574</phone>
      <email>coordpesq@cardresearch.org</email>
    </contact>
    <investigator>
      <last_name>Gilmar Reis, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Pontificia Universidade Catolica de Minas Gerais</name>
      <address>
        <city>Belo Horizonte</city>
        <state>Minas Gerais</state>
        <zip>30535901</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Eduardo Silva, MD, PhD</last_name>
      <email>duduaugusto1@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Eduardo Silva, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fundo Municipal de Saúde de Betim</name>
      <address>
        <city>Betim</city>
        <state>Minas Gerais</state>
        <zip>32600412</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniela Silva, MD, PhD</last_name>
      <phone>5531984923130</phone>
      <email>daninhamed@yahoo.com.br</email>
    </contact>
    <investigator>
      <last_name>Daniela Silva, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universidade Federal de Ouro Preto</name>
      <address>
        <city>Ouro Preto</city>
        <state>Minas Gerais</state>
        <zip>35400000</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Leonardo Savassi, MD, PhD</last_name>
      <email>leosavassi@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Leonardo Savassi, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>May 23, 2020</study_first_submitted>
  <study_first_submitted_qc>May 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>January 25, 2021</last_update_submitted>
  <last_update_submitted_qc>January 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cardresearch</investigator_affiliation>
    <investigator_full_name>Gilmar Reis</investigator_full_name>
    <investigator_title>Director - Outpatient Research Clinic</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Respiratory Tract Infections</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Lopinavir</mesh_term>
    <mesh_term>Hydroxychloroquine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 3, 2021</submitted>
    <returned>August 9, 2021</returned>
  </pending_results>
  <!-- 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/NCT04403100
org study id: COVID19_AMB_Brasil
nct id: NCT04403100
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The COVID-19 pandemic has been characterized by high morbidity and mortality, especially in
      certain subgroups of patients. To date, no treatment has been shown to be effective in
      controlling this disease in hospitalized patients with moderate and / or severe cases of this
      disease. Hydroxychloroquine and lopinavir / ritonavir have been shown to inhibit SARS-CoV
      viral replication in experimental severe acute respiratory symptoms models and have similar
      activity against SARS-CoV2. Although widely used in studies of critically ill patients, to
      date, no study has demonstrated its role on the treatment of high-risk, newly diagnosed
      patients with COVID-19 and mild symptoms.
In December 2019 a series of viral pneumonia cases were reported in the city of Wuhan, China.
      A new subtype of coronavirus has been identified as the causative agent of this condition. On
      February 11, 43,103 cases had already been described and on this day the World Health
      Organization (WHO) named this disease as COVID-19. With. The disease had spread out to
      several countries on different continents and on March 11, WHO declared a state of worldwide
      pandemic. Today (April 25, 2020) there are 2,719,897 cases and 187,705 deaths documented,
      with a global case-fatality ratio of 6.9%.

      To date, no treatment has been identified as effective in combating this disease which has
      been identified as with high mortality, therefore there are no specific therapeutic options.
      So far, efforts have been focused on the treatment of patients hospitalized with dyspnea and,
      although several promising drugs are being evaluated, none has demonstrated effectiveness in
      reducing morbidity and mortality at this stage of the disease, suggesting that perhaps the
      best time to use medications either before the onset of severe symptoms of respiratory
      distress.

      Thus, we propose the use of two drugs which experimentally have shown activity against
      SARS-CoV2 and being used in severely ill patients with COVID-19. Our hypothesis is that
      perhaps using such drugs before onset of complications will allow better outcomes on this
      patient population.
allocation: Randomized
intervention model: Factorial Assignment
intervention model description: Patients will be randomly allocated to one of four treatment arms in a 1:1:1:1 ratio:
Lopinavir / Ritonavir
Hydroxychloroquine
Lopinavir / Ritonavir + Hydroxychloroquine
Placebo.
We will use a centralized random allocation schedule, generated by computer and implemented using an online remote access system. Randomization will be stratified by participating basic health unit.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The investigational medical product will be packaged in similar bottles by a third party who will keep the allocation confidential until the end of the study. The bottles will be sealed and identified as "Research Product A, B and C" and with different colored labels. They will be randomly allocated among the participants. The research subjects, medical assistance, administrative and health staff will not have access to the contents of the bottles. The Arm Lopinavir/ ritonavir plus hydroxychloroquine will receive two of such bottles.
At the end of the study, after the statistical analysis and DMSB meeting, it will then be requested from third party documentation on content of each bottle and then have arms identified.
measure: Proportion of participants who were hospitalized for progression of COVID-19 disease
time frame: Measuring during 28-day period since randomization (Intention to treat analysis)
description: Hospitalization is defined as at least 24 hours of acute care in a hospital or similar acute care facility (emergency settings, temporary emergency facilities created for acute care of COVID-19 pandemic)
measure: Proportion of participants who died due to COVID-19 progression and/ or complications
time frame: Measuring during 28-day period since randomization (Intention to treat analysis)
measure: Proportion of participants with viral load change on 03, 07, 10 and 14 after randomization
time frame: Measuring during 14-day period since randomization
description: Viral load change on 03, 07, 10 and 14 after randomization (200 patients per arm)
measure: Time to clinical improvement
time frame: Measuring during 28-day period since randomization
description: Proportion of participants with clinical improvement, defined as normalization of temperature, Respiratory rate, SaO2, and cough relief (> 50% compared to baseline measured on a visual analog scale) in the last 72 hours.
measure: Time to clinical failure
time frame: Measuring during 28-day period since randomization
description: Proportion of participants with clinical improvement, defined as as time to need for hospitalization due to dyspnea, death, need for mechanical ventilation, shock and need for vasoactive amines;
measure: Hospitalization for any cause
time frame: Measuring during 28-day period since randomization
description: Proportion of participants with hospitalization for any cause
measure: Proportion of participants who died due to pulmonary complications
time frame: Measuring during 28-day period since randomization
measure: Proportion of participants who died due to cardiovascular complications
time frame: Measuring during 28-day period since randomization
measure: Proportion of participants who presented with adverse events
time frame: Measuring during 28-day period since randomization
description: Evaluation of adverse events evaluated as associated to any of study arms
measure: Time to improvement on respiratory scale symptoms
time frame: Measuring during 28-day period since randomization
description: Proportion of participants who presented sustained improvement on respiratory scale defined as at least 48 hours of improvement.
measure: proportion of non-adherent participants to any of study drugs
time frame: Measuring during 10-day period since randomization
arm group label: Hydroxychloroquine Sulfate
arm group type: Active Comparator
description: Hydroxychloroquine 400 mg. Loading oral dose of 800 mg followed by orally dose of 400 mg/ day for the following 10 days
arm group label: Lopinavir/ Ritonavir
arm group type: Active Comparator
description: Lopinavir Ritonavir 200/ 50 mg Loading oral dose of 800/ 200 mg twice a day on day 1 followed by 400/100 mg orally twice a day for the following 9 days
arm group label: Hydroxychloroquine plus Lopinavir/ Ritonavir
arm group type: Active Comparator
description: Hydroxychloroquine 400 mg. Loading oral dose of 800 mg followed by orally dose of 400 mg/ day for the following 10 days
Plus
Lopinavir Ritonavir 200/ 50 mg Loading oral dose of 800/ 200 mg twice a day on day 1 followed by 400/100 mg orally twice a day for the following 9 days
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
Twice a day from day 1 through day 10.
intervention type: Drug
intervention name: Hydroxychloroquine Sulfate Tablets
description: Tablets of 400 mg: Loading dose of 02 tablets followed by one tablet of 400 mg orally on the following 09 days
arm group label: Hydroxychloroquine Sulfate
intervention type: Drug
intervention name: Lopinavir/ Ritonavir Oral Tablet
description: tablets of 200/ 50 mg; Loading dose of 04 tablets twice a day on day 1 followed by two tablets twice a day on the following 09 days
arm group label: Lopinavir/ Ritonavir
intervention type: Drug
intervention name: Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets
description: Hydroxychloroquine Oral Tablet 400 mg: Loading dose of 02 tablets followed by one tablet of 400 mg orally on the following 09 days
plus
Lopinavir/ Ritonavir Oral Tablet of 200/ 50 mg: Loading dose of 04 tablets twice a day on day 1 followed by two tablets twice a day on the following 09 days
arm group label: Hydroxychloroquine plus Lopinavir/ Ritonavir
intervention type: Drug
intervention name: Placebo
description: Placebo tablets - 01 tablet twice daily from day 01 through day 10.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gilmar Reis, MD, PhD
role: Principal Investigator
affiliation: Cardresearch - Cardiologia Assistencial e de Pesquisa LTDA
last name: Gilmar Reis, MD, PhD
phone: +5531332416574
email: greisbh@uol.com.br
last name: Rosemary Oliveira, SC
phone: +5531992636703
email: roliveira@cardresearch.org
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Cardresearch
investigator full name: Gilmar Reis
investigator title: Director - Outpatient Research Clinic
mesh term: Infections
mesh term: Communicable Diseases
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Respiratory Tract Infections
mesh term: Virus Diseases
mesh term: Severe Acute Respiratory Syndrome
mesh term: Ritonavir
mesh term: Lopinavir
mesh term: Hydroxychloroquine
sharing ipd: No
submitted: August 3, 2021
returned: August 9, 2021