<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/NCT04428268</url>
  </required_header>
  <id_info>
    <org_study_id>IF20-00003</org_study_id>
    <nct_id>NCT04428268</nct_id>
  </id_info>
  <brief_title>Chloroquine + Losartan Compared to Chloroquine Alone for the Treatment of COVID-19 Pneumonia</brief_title>
  <official_title>Phase II, Randomized, Double-blind, Controlled Clinical Trial Evaluating the Efficacy and Safety of Chloroquine + Low Dose Losartan Compared to Chloroquine Monotherapy in Subjects With SARS-CoV-2 Pneumonia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Universitario Dr. Jose E. Gonzalez</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Universitario Dr. Jose E. Gonzalez</source>
  <oversight_info>
    <has_dmc>No</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>
      Study design Phase 2, double blinded, single-center, 1:1 randomized clinical trial of&#xD;
      Chloroquine vs Chloroquine/losartan for the treatment of SARS-CoV-2 pneumonia in&#xD;
      non-critically ill subjects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design Phase 2, blinded, single-center, 1: 1 randomized clinical trial for the&#xD;
      treatment of SARS-CoV-2 pneumonia in non-critically ill subjects. Two of the co-investigators&#xD;
      and the data analyst will remain blind to group allocation until after statistical analysis.&#xD;
&#xD;
      The groups will consist of subjects receiving in one arm PO Chloroquine 450mg every 12 hours&#xD;
      and in the other arm, in addition to chloroquine, PO Losartan 25mg every 24 hours. Study&#xD;
      drugs will be administered for a total of 10 days enterally.&#xD;
&#xD;
      Baseline demographics and clinical characteristics will be registered and periodically during&#xD;
      the study.&#xD;
&#xD;
      nasopharyngeal swabs will be taken every 48hrs during hospitalization to determine the&#xD;
      presences and viral load of SARS-CoV-2, and daily EKG for QT interval monitoring.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    evidence showed chloroquine is not effective against COVID-19&#xD;
  </why_stopped>
  <start_date type="Actual">March 10, 2020</start_date>
  <completion_date type="Actual">February 16, 2021</completion_date>
  <primary_completion_date type="Actual">June 10, 2020</primary_completion_date>
  <phase>Phase 2</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>double blind randomized clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
    <masking_description>investigator will not be aware of the treatments or outcomes until the end of the study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Overall mortality</measure>
    <time_frame>28 days</time_frame>
    <description>Determine all-cause mortality up to 28 days after randomization of Chloroquine Phosphate Compared to Chloroquine Phosphate plus Losartan in Non-Critically Ill Patients with SARS-CoV-2 Pneumonia.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical outcome assessment</measure>
    <time_frame>28 days</time_frame>
    <description>Compare the clinical outcome of Chloroquine Phosphate treatment vs Chloroquine Phosphate plus Losartan in the follow-up visit at the end of treatment. Acording to NIH and FDA definitions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>28 days</time_frame>
    <description>Assess the adverse events associated to chloroquine and chloroquine plus losartan at 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to negative SARS-CoV-2 test</measure>
    <time_frame>28 days</time_frame>
    <description>Time to negative Polymerase chain reaction (PCR) test from baseline: testing every 48hrs until a negative result</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>COVID-19 Pneumonia</condition>
  <arm_group>
    <arm_group_label>Chloroquine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive chloroquine phosphate 450 mg every 12 hours orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chloroquine plus losartan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive Chloroquine phosphate 450mg orally every 12hrs plus Losartan 25mg orally every 12hrs</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chloroquine Phosphate Tablets</intervention_name>
    <description>Orally administered</description>
    <arm_group_label>Chloroquine</arm_group_label>
    <arm_group_label>Chloroquine plus losartan</arm_group_label>
    <other_name>Losartan tablets</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men or women ≥18 years.&#xD;
&#xD;
          2. Oral tolerance or access for enteral administration of medication.&#xD;
&#xD;
          3. PCR or IgM for SARS-CoV-2 positive.&#xD;
&#xD;
          4. Negative pregnancy test in case of a woman of reproductive age.&#xD;
&#xD;
          5. Signature of a document proving informed consent.&#xD;
&#xD;
          6. Hospital admission for SARS-CoV-2 pneumonia.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. New alteration of the state of alert that does not revert after interventions 60&#xD;
             minutes after hospital admission.&#xD;
&#xD;
          2. Mean Arterial Pressure (MAP) ≤ 65mmHg despite initial resuscitation on arrival at the&#xD;
             centre.&#xD;
&#xD;
          3. History of allergy to chloroquine, hydroxychloroquine, piperaquine or primaquine.&#xD;
&#xD;
          4. Known patient with hearing loss.&#xD;
&#xD;
          5. Received chloroquine or hydroxychloroquine in the last 3 months.&#xD;
&#xD;
          6. Patients with cirrhosis or elevation of aspartate transaminase (AST) or alanine&#xD;
             transaminase (ALT) greater than three times the upper normal limit.&#xD;
&#xD;
          7. Patients with calculated glomerular filtration rate by Modification of Diet in Renal&#xD;
             Disease study equation (MDRD) &lt; 30ml/min 1.73 m2.&#xD;
&#xD;
          8. Patients known to be deficient in 6-phosphate dehydrogenase&#xD;
&#xD;
          9. Patients known to have retinopathy or macular disease.&#xD;
&#xD;
         10. History of acute myocardial infarction in the last 6 months, unstable angina,&#xD;
             ventricular tachycardia, ventricular fibrillation or class III-IV heart failure&#xD;
             according to New York Heart Association.&#xD;
&#xD;
         11. Electrocardiogram QTc interval ≥ 480 ms.&#xD;
&#xD;
         12. Patients with hypomagnesemia or uncorrected hypokalemia.&#xD;
&#xD;
         13. Patients with a history of psychiatric illness.&#xD;
&#xD;
         14. Patients who are pregnant or nursing.&#xD;
&#xD;
         15. Patients taking quinolones, dextropropoxyphene, amiodarone, flecainide, cisapride,&#xD;
             domperidone, atazanavir or lopinavir.&#xD;
&#xD;
         16. Patients with acute pancreatitis.&#xD;
&#xD;
         17. Patients who the investigators deem unsuitable for participation in the clinical&#xD;
             trial.&#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>Adrian Camacho Ortiz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario &quot;Dr. Jose Eleuterio Gonzalez&quot;, UANL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitario José E. Gonzalez</name>
      <address>
        <city>Monterrey</city>
        <state>Nuevo Leon</state>
        <zip>64460</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>April 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>February 16, 2021</last_update_submitted>
  <last_update_submitted_qc>February 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Universitario Dr. Jose E. Gonzalez</investigator_affiliation>
    <investigator_full_name>Dr. Adrian Camacho-Ortiz</investigator_full_name>
    <investigator_title>Head of the Infectious Disease Department</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>SARS-CoV-2 pneumonia</keyword>
  <keyword>Chloroquine phosphate</keyword>
  <keyword>Losartan</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chloroquine</mesh_term>
    <mesh_term>Chloroquine diphosphate</mesh_term>
    <mesh_term>Losartan</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04428268
org study id: IF20-00003
nct id: NCT04428268
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Study design Phase 2, double blinded, single-center, 1:1 randomized clinical trial of
      Chloroquine vs Chloroquine/losartan for the treatment of SARS-CoV-2 pneumonia in
      non-critically ill subjects
Study design Phase 2, blinded, single-center, 1: 1 randomized clinical trial for the
      treatment of SARS-CoV-2 pneumonia in non-critically ill subjects. Two of the co-investigators
      and the data analyst will remain blind to group allocation until after statistical analysis.

      The groups will consist of subjects receiving in one arm PO Chloroquine 450mg every 12 hours
      and in the other arm, in addition to chloroquine, PO Losartan 25mg every 24 hours. Study
      drugs will be administered for a total of 10 days enterally.

      Baseline demographics and clinical characteristics will be registered and periodically during
      the study.

      nasopharyngeal swabs will be taken every 48hrs during hospitalization to determine the
      presences and viral load of SARS-CoV-2, and daily EKG for QT interval monitoring.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: double blind randomized clinical trial
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
masking description: investigator will not be aware of the treatments or outcomes until the end of the study
measure: Overall mortality
time frame: 28 days
description: Determine all-cause mortality up to 28 days after randomization of Chloroquine Phosphate Compared to Chloroquine Phosphate plus Losartan in Non-Critically Ill Patients with SARS-CoV-2 Pneumonia.
measure: Clinical outcome assessment
time frame: 28 days
description: Compare the clinical outcome of Chloroquine Phosphate treatment vs Chloroquine Phosphate plus Losartan in the follow-up visit at the end of treatment. Acording to NIH and FDA definitions
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 28 days
description: Assess the adverse events associated to chloroquine and chloroquine plus losartan at 28 days
measure: Time to negative SARS-CoV-2 test
time frame: 28 days
description: Time to negative Polymerase chain reaction (PCR) test from baseline: testing every 48hrs until a negative result
arm group label: Chloroquine
arm group type: Active Comparator
description: Patients will receive chloroquine phosphate 450 mg every 12 hours orally
arm group label: Chloroquine plus losartan
arm group type: Experimental
description: Patients will receive Chloroquine phosphate 450mg orally every 12hrs plus Losartan 25mg orally every 12hrs
intervention type: Drug
intervention name: Chloroquine Phosphate Tablets
description: Orally administered
arm group label: Chloroquine
arm group label: Chloroquine plus losartan
other name: Losartan tablets
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Adrian Camacho Ortiz, MD
role: Principal Investigator
affiliation: Hospital Universitario "Dr. Jose Eleuterio Gonzalez", UANL
facility: 
country: Mexico
responsible party type: Principal Investigator
investigator affiliation: Hospital Universitario Dr. Jose E. Gonzalez
investigator full name: Dr. Adrian Camacho-Ortiz
investigator title: Head of the Infectious Disease Department
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Chloroquine
mesh term: Chloroquine diphosphate
mesh term: Losartan