<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/NCT04491994</url>
  </required_header>
  <id_info>
    <org_study_id>Sultan Mehmood Kamran 2</org_study_id>
    <nct_id>NCT04491994</nct_id>
  </id_info>
  <brief_title>Clearing the Fog: Is Hydroxychloroquine Effective in Reducing COVID-19 Progression</brief_title>
  <acronym>COVID-19</acronym>
  <official_title>Clearing the Fog: Is HCQ Effective in Reducing COVID-19 progression-a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UNICEF</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pak Emirates Military Hospital Rawalpindi, Pakistan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>UNICEF</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>
      Brief Summary: Purpose of this study is to evaluate efficacy of hydroxychloroquine (HCQ) in&#xD;
      reducing progression of Corona Virus Disease 2019 (COVID - 19) and achieving viral clearance.&#xD;
&#xD;
      Condition or disease :I COVID-19 ntervention/treatment :Drug: Hydroxychloroquine Sulfate&#xD;
      Phase: Phase III&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study explores efficacy of HCQ (400mg BD on D0 and 200mg BD D1-D5) in reducing&#xD;
      progression of Mild Covid-19 patients and decreasing viral load.&#xD;
&#xD;
      Participants of study will be randomized 2:1 to receive either Active drug or standard of&#xD;
      care (SOC) treatment respectively. We aim to demonstrate reduced COVID-19 progression and&#xD;
      early viral clearance in individuals on HCQ therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 10, 2020</start_date>
  <completion_date type="Actual">May 31, 2020</completion_date>
  <primary_completion_date type="Actual">May 31, 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>Randomization rules were designed by Dr. Wasim Alamgir together with principal investigators and implemented by an independent statistician who was not involved in data analysis. Stratified random sampling was applied to stratify all eligible patients according to age, gender and comorbidities. Computerized random number generator was used and allocation was done in 2:1 sequence. Cards with each group assignment number randomly generated by computer were placed in sequentially numbered envelopes that were opened as the patients were enrolled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Neither patients, nor investigators, nor statisticians were masked to treatment assignment. Lab staff who performed sampling for PCR, basic blood tests and other routine measurement were unaware of treatment information.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Progression</measure>
    <time_frame>5 days</time_frame>
    <description>After start of treatment, development of fever &gt; 101 F for &gt; 72 hours, shortness of breath by minimal exertion (10-Step walk test), derangement of basic lab parameters (ALC &lt; 1000 or raised CRP) or appearance of infiltrates on CXR during course of treatment was labeled as progression irrespective of PCR status</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Viral Clearance</measure>
    <time_frame>14 days</time_frame>
    <description>PCR negativity on day 7 and 14 after admission</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">540</enrollment>
  <condition>Covid19</condition>
  <condition>Progression</condition>
  <arm_group>
    <arm_group_label>Standard of Care (SOC)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients selected in supportive arm will be given daily standard doses of oral Vit C (2g), Vit D (alfacalcidiol 1µg), Zinc (50mg) and paracetamol (as required).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCQ arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients selected in experimental arm will be given Tab HCQ (400mg BD on D0 followed by 200mg BD D1-D5) in addition to supportive treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HCQ</intervention_name>
    <description>Tab HCQ 400mg 12 hourly day 0 followed by tab HCQ 200mg 12 hrly for next 5 days</description>
    <arm_group_label>HCQ arm</arm_group_label>
    <other_name>HCQ + Standard of Care (SOC)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Mild Corona virus disease (COVID-19)&#xD;
&#xD;
          -  PCR confirmed infection&#xD;
&#xD;
          -  Hospital admitted patients&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Moderate, severe and critical COVID-19&#xD;
&#xD;
          -  day 0 CRP greater than 6mg/dl, ALC &lt; 1000 or evidence of infiltrates on X-ray chest&#xD;
&#xD;
          -  comorbidity with life expectancy less than 6 months&#xD;
&#xD;
          -  Contraindications to HCQ therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Imran m Fazal, FCPS</last_name>
    <role>Study Director</role>
    <affiliation>Pak Emirates Military Hospital (PEMH) Rawalpindi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pak Emirates Military Hospital</name>
      <address>
        <city>Rawalpindi</city>
        <state>Punjab</state>
        <zip>46000</zip>
        <country>Pakistan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <reference>
    <citation>Biot C, Daher W, Chavain N, Fandeur T, Khalife J, Dive D, De Clercq E. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem. 2006 May 4;49(9):2845-9. doi: 10.1021/jm0601856.</citation>
    <PMID>16640347</PMID>
  </reference>
  <reference>
    <citation>Murray JJ, Lee MS. Re: Marmor et al.: American Academy of Ophthalmology Statement: Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 Revision). (Ophthalmology 2016;123:1386-1394). Ophthalmology. 2017 Mar;124(3):e28-e29. doi: 10.1016/j.ophtha.2016.06.062. No abstract available.</citation>
    <PMID>28219513</PMID>
  </reference>
  <reference>
    <citation>Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.</citation>
    <PMID>32205204</PMID>
  </reference>
  <reference>
    <citation>Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020 Jul 1;75(7):1667-1670. doi: 10.1093/jac/dkaa114.</citation>
    <PMID>32196083</PMID>
  </reference>
  <reference>
    <citation>Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Jul 28;71(15):732-739. doi: 10.1093/cid/ciaa237.</citation>
    <PMID>32150618</PMID>
  </reference>
  <reference>
    <citation>Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73. doi: 10.5582/bst.2020.01047. Epub 2020 Feb 19.</citation>
    <PMID>32074550</PMID>
  </reference>
  <reference>
    <citation>Chen J, Liu D, Liu L, Liu P, Xu Q, Xia L, Ling Y, Huang D, Song S, Zhang D, Qian Z, Li T, Shen Y, Lu H. [A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020 May 25;49(2):215-219. doi: 10.3785/j.issn.1008-9292.2020.03.03. Chinese.</citation>
    <PMID>32391667</PMID>
  </reference>
  <reference>
    <citation>Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, Edwards KM, Gandhi R, Muller WJ, O'Horo JC, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin Infect Dis. 2020 Apr 27:ciaa478. doi: 10.1093/cid/ciaa478. Online ahead of print.</citation>
    <PMID>32338708</PMID>
  </reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <results_first_submitted>July 31, 2020</results_first_submitted>
  <results_first_submitted_qc>August 18, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 21, 2020</results_first_posted>
  <last_update_submitted>August 18, 2020</last_update_submitted>
  <last_update_submitted_qc>August 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>UNICEF</investigator_affiliation>
    <investigator_full_name>sultan mehmood kamran</investigator_full_name>
    <investigator_title>Classified Medical specialist</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>viral clearance</keyword>
  <keyword>, mild infection</keyword>
  <keyword>disease progression</keyword>
  <keyword>trial</keyword>
  <keyword>HCQ</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Disease Progression</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>data can be shared on demand in SPSS sheet</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>any time when asked</ipd_time_frame>
    <ipd_access_criteria>by email</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 15, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/94/NCT04491994/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Enrollment during 10th April to 31st May 2020 at department of Pulmonology, Pakistan Emirates Military Hospital (PEMH) Pakistan.</recruitment_details>
      <pre_assignment_details>672 confirmed PCR positive cases were assessed for eligibility. 132 did not meet selection criteria and excluded.Later,15 withdrew consent and 5 became symptomatic. During follow up 13 patients were found to be deviated from advised therapy and 7 were lost to follow up yielding a final study population of 500.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Control Group</title>
          <description>Standard of care (SOC) treatment comprised of oral Vit C, oral Zinc, oral Vit-D and tablet Paracetamol (for body aches/fever), intravenous fluids, hemodynamic monitoring, and laboratory testing for SARS-CoV-2 and baseline blood parameters.</description>
        </group>
        <group group_id="P2">
          <title>Intervention Group</title>
          <description>Patients selected in experimental arm will be given standard doses of tab HCQ in addition to standard of care (SOC) treatment. side effects will be monitored&#xD;
HCQ: Tab HCQ 400mg 12 hourly day 0 followed by tab HCQ 200mg 12 hrly for next 5 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="180"/>
                <participants group_id="P2" count="360"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="151"/>
                <participants group_id="P2" count="349"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>developed fever &gt; 3 days</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>sample size calculation was done and 540 patients enrolled</population>
      <group_list>
        <group group_id="B1">
          <title>Supportive Arm</title>
          <description>Patients selected in supportive arm will be given standard doses of oral Vit C, Vit D, Zinc and panadol</description>
        </group>
        <group group_id="B2">
          <title>HCQ Arm</title>
          <description>Patients selected in experimental arm will be given standard doses of tab HCQ in addition to supportive treatment. side effects will be monitored&#xD;
HCQ: Tab HCQ 400mg 12 hourly day 0 followed by tab HCQ 200mg 12 hrly for next 5 days</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="180"/>
            <count group_id="B2" value="360"/>
            <count group_id="B3" value="540"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="180"/>
                    <count group_id="B2" value="360"/>
                    <count group_id="B3" value="540"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="180"/>
                    <measurement group_id="B2" value="360"/>
                    <measurement group_id="B3" value="540"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="180"/>
                    <count group_id="B2" value="360"/>
                    <count group_id="B3" value="540"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="170"/>
                    <measurement group_id="B2" value="336"/>
                    <measurement group_id="B3" value="506"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Pakistan</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="180"/>
                    <count group_id="B2" value="360"/>
                    <count group_id="B3" value="540"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="180"/>
                    <measurement group_id="B2" value="360"/>
                    <measurement group_id="B3" value="540"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Progression</title>
        <description>After start of treatment, development of fever &gt; 101 F for &gt; 72 hours, shortness of breath by minimal exertion (10-Step walk test), derangement of basic lab parameters (ALC &lt; 1000 or raised CRP) or appearance of infiltrates on CXR during course of treatment was labeled as progression irrespective of PCR status</description>
        <time_frame>5 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC)</title>
            <description>Standard of care (SOC) treatment comprised of daily oral Vit C (2gms), oral Zinc (50mg), oral Vit-D (alfacalcidol 1ug) and tablet Paracetamol (for body aches/fever), intravenous fluids, hemodynamic monitoring, and laboratory testing for SARS-CoV-2 and baseline blood parameters</description>
          </group>
          <group group_id="O2">
            <title>Intervention Group</title>
            <description>Patients selected in intervention arm were given HCQ in addition to standard of care treatment. After 12 hours of randomization HCQ was given. Standard dose of HCQ was 400 mg by mouth twice a day for day one followed by 200 mg 12 hourly for next 5 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Progression</title>
          <description>After start of treatment, development of fever &gt; 101 F for &gt; 72 hours, shortness of breath by minimal exertion (10-Step walk test), derangement of basic lab parameters (ALC &lt; 1000 or raised CRP) or appearance of infiltrates on CXR during course of treatment was labeled as progression irrespective of PCR status</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="151"/>
                <count group_id="O2" value="349"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Viral Clearance</title>
        <description>PCR negativity on day 7 and 14 after admission</description>
        <time_frame>14 days</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>14 days after first dose of HCQ or SOC</time_frame>
      <desc>Daily ECG, visual assessment, and Blood complete picture</desc>
      <group_list>
        <group group_id="E1">
          <title>Control Group</title>
          <description>Standard of care (SOC) treatment comprised of oral Vit C, oral Zinc, oral Vit-D and tablet Paracetamol (for body aches/fever), intravenous fluids, hemodynamic monitoring, and laboratory testing for SARS-CoV-2 and baseline blood parameters.</description>
        </group>
        <group group_id="E2">
          <title>Intervention Group</title>
          <description>Patients selected in experimental arm will be given standard doses of tab HCQ in addition to standard of care (SOC) treatment. side effects will be monitored&#xD;
HCQ: Tab HCQ 400mg 12 hourly day 0 followed by tab HCQ 200mg 12 hrly for next 5 days</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="151"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="349"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="151"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="349"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="151"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="349"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Sultan Mehmood Kamran</name_or_title>
      <organization>Pak Emirates Military Hospital (PEMH) Rawalpindi</organization>
      <phone>+923008501100</phone>
      <email>sultanmajoka79@hotmail.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04491994
org study id: Sultan Mehmood Kamran 2
nct id: NCT04491994
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Brief Summary: Purpose of this study is to evaluate efficacy of hydroxychloroquine (HCQ) in
      reducing progression of Corona Virus Disease 2019 (COVID - 19) and achieving viral clearance.

      Condition or disease :I COVID-19 ntervention/treatment :Drug: Hydroxychloroquine Sulfate
      Phase: Phase III
This study explores efficacy of HCQ (400mg BD on D0 and 200mg BD D1-D5) in reducing
      progression of Mild Covid-19 patients and decreasing viral load.

      Participants of study will be randomized 2:1 to receive either Active drug or standard of
      care (SOC) treatment respectively. We aim to demonstrate reduced COVID-19 progression and
      early viral clearance in individuals on HCQ therapy.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomization rules were designed by Dr. Wasim Alamgir together with principal investigators and implemented by an independent statistician who was not involved in data analysis. Stratified random sampling was applied to stratify all eligible patients according to age, gender and comorbidities. Computerized random number generator was used and allocation was done in 2:1 sequence. Cards with each group assignment number randomly generated by computer were placed in sequentially numbered envelopes that were opened as the patients were enrolled
primary purpose: Treatment
masking: None (Open Label)
masking description: Neither patients, nor investigators, nor statisticians were masked to treatment assignment. Lab staff who performed sampling for PCR, basic blood tests and other routine measurement were unaware of treatment information.
measure: Number of Participants With Progression
time frame: 5 days
description: After start of treatment, development of fever > 101 F for > 72 hours, shortness of breath by minimal exertion (10-Step walk test), derangement of basic lab parameters (ALC < 1000 or raised CRP) or appearance of infiltrates on CXR during course of treatment was labeled as progression irrespective of PCR status
measure: Viral Clearance
time frame: 14 days
description: PCR negativity on day 7 and 14 after admission
arm group label: Standard of Care (SOC)
arm group type: No Intervention
description: Patients selected in supportive arm will be given daily standard doses of oral Vit C (2g), Vit D (alfacalcidiol 1µg), Zinc (50mg) and paracetamol (as required).
arm group label: HCQ arm
arm group type: Experimental
description: Patients selected in experimental arm will be given Tab HCQ (400mg BD on D0 followed by 200mg BD D1-D5) in addition to supportive treatment
intervention type: Drug
intervention name: HCQ
description: Tab HCQ 400mg 12 hourly day 0 followed by tab HCQ 200mg 12 hrly for next 5 days
arm group label: HCQ arm
other name: HCQ + Standard of Care (SOC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Imran m Fazal, FCPS
role: Study Director
affiliation: Pak Emirates Military Hospital (PEMH) Rawalpindi
facility: 
country: Pakistan
citation: Biot C, Daher W, Chavain N, Fandeur T, Khalife J, Dive D, De Clercq E. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem. 2006 May 4;49(9):2845-9. doi: 10.1021/jm0601856.
PMID: 16640347
citation: Murray JJ, Lee MS. Re: Marmor et al.: American Academy of Ophthalmology Statement: Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 Revision). (Ophthalmology 2016;123:1386-1394). Ophthalmology. 2017 Mar;124(3):e28-e29. doi: 10.1016/j.ophtha.2016.06.062. No abstract available.
PMID: 28219513
citation: Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.
PMID: 32205204
citation: Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020 Jul 1;75(7):1667-1670. doi: 10.1093/jac/dkaa114.
PMID: 32196083
citation: Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Jul 28;71(15):732-739. doi: 10.1093/cid/ciaa237.
PMID: 32150618
citation: Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73. doi: 10.5582/bst.2020.01047. Epub 2020 Feb 19.
PMID: 32074550
citation: Chen J, Liu D, Liu L, Liu P, Xu Q, Xia L, Ling Y, Huang D, Song S, Zhang D, Qian Z, Li T, Shen Y, Lu H. [A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020 May 25;49(2):215-219. doi: 10.3785/j.issn.1008-9292.2020.03.03. Chinese.
PMID: 32391667
citation: Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, Edwards KM, Gandhi R, Muller WJ, O'Horo JC, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin Infect Dis. 2020 Apr 27:ciaa478. doi: 10.1093/cid/ciaa478. Online ahead of print.
PMID: 32338708
responsible party type: Principal Investigator
investigator affiliation: UNICEF
investigator full name: sultan mehmood kamran
investigator title: Classified Medical specialist
mesh term: COVID-19
mesh term: Disease Progression
sharing ipd: Yes
ipd description: data can be shared on demand in SPSS sheet
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: any time when asked
ipd access criteria: by email
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 