<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/NCT04459286</url>
  </required_header>
  <id_info>
    <org_study_id>NACOVID</org_study_id>
    <nct_id>NCT04459286</nct_id>
  </id_info>
  <brief_title>The Nitazoxanide Plus Atazanavir for COVID-19 Study</brief_title>
  <acronym>NACOVID</acronym>
  <official_title>A Randomized, Open Label Trial to Investigate the Efficacy and Safety of Nitazoxanide Plus Atazanavir/Ritonavir for the Treatment of COVID-19: a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Obafemi Awolowo University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Liverpool</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>African Centre of Excellence for Genomics of Infectious Diseases</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Infectious Disease Hospital Olodo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Obafemi Awolowo University Teaching Hospitals Complex</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Osun State Ministry of Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Olabisi Onabanjo University Teaching Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Obafemi Awolowo University</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>
      Since the outbreak of the novel coronavirus disease in 2019 (COVID-19), an unprecedented&#xD;
      global search for potential therapeutics and vaccines is ongoing. In this study, a&#xD;
      combination of two drugs that have been shown to be effective against the germ that causes&#xD;
      COVID-19 in the laboratory will be tested in patients diagnosed with moderate to severe&#xD;
      COVID-19. One of the drugs is called nitazoxanide and the second is atazanavir/ritonavir.&#xD;
      Nitazoxanide has been used for the treatment of diarrhea since 2004 while&#xD;
      atazanavir/ritonavir was approved for HIV treatment in 2003. They are known to be safe in&#xD;
      humans.&#xD;
&#xD;
      In this pilot study, 98 COVID-19 patients will be recruited into two groups. The 49 patients&#xD;
      in group 1 will receive the standard of care determined by their primary care providers while&#xD;
      the 49 patients in group 2 will receive both the standard of care combined with the two study&#xD;
      drugs. Patients in group 2 will receive the study drugs for 14 days and all patients will be&#xD;
      monitored for a total of 28 days.&#xD;
&#xD;
      The time it takes for the germ that causes COVID-19 to be completely removed from the body&#xD;
      (in nasal secretions) and the time to clinical improvement will be monitored in all patients&#xD;
      and compared between the two groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      COVID-19 caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) is an&#xD;
      unprecedented global public health challenge which as at July 1, 2020 has spread to over 210&#xD;
      countries with over 10.6 million cases resulting in 514,808 deaths. More than 1500 clinical&#xD;
      trials are currently ongoing in an unprecedented global search for potential therapeutics and&#xD;
      vaccines. With increasing number of cases reported in low- and middle-income countries and&#xD;
      and the possibility of a second wave of infections in countries where the pandemic appears to&#xD;
      have slowed, studies to investigate promising therapies are urgently needed, especially those&#xD;
      that can significantly reduce time to viral clearance and mortality. Shortening SARS-CoV-2&#xD;
      clearance time will lower treatment cost and reduce the economic impact of the pandemic.&#xD;
&#xD;
      The purpose of this phase 2 trial is to investigate the efficacy and safety of repurposed&#xD;
      antiprotozoal and antiretroviral drugs, nitazoxanide and atazanavir/ritonavir, in achievement&#xD;
      of SARS-CoV-2 PCR negativity and shorten the time to clinical improvement in patients&#xD;
      diagnosed with moderate to severe COVID-19. The selection of candidates for this COVID-19&#xD;
      drug repurposing trial was guided by three pharmacological considerations: (1) demonstration&#xD;
      of in-vitro anti-SARS-CoV-2 activity at doses shown or predicted to be tolerated by humans,&#xD;
      (2) the feasibility of achieving effective concentration in relevant compartments, and (3)&#xD;
      established human safety record.&#xD;
&#xD;
      This is a pilot phase 2, open label randomized controlled trial. A total of 98 patients with&#xD;
      confirmed COVID-19 diagnosis (defined as SARS-CoV-2 polymerase chain reaction (PCR) positive&#xD;
      nasopharyngeal swab) will be recruited from participating treatment centres. Participants&#xD;
      will be randomised to receive either the standard of care (SOC) plus nitazoxanide for 14&#xD;
      days, starting from day 1 or the SOC alone for 14 days.&#xD;
&#xD;
      Participants will be recruited within 2 days of admission into COVID-19 treatment centre.&#xD;
      Before enrollment, they will be given adequate information about the trial, opportunity to&#xD;
      ask questions, and sufficient time to consider participation. Before any screening&#xD;
      procedures, a written consent will be obtained from each eligible subject who agrees to&#xD;
      participate in the trial. Participants will then be randomly allocated 1:1 to receive either&#xD;
      the SOC alone (control group) or SOC plus study drug (intervention group). Parallel&#xD;
      assignment will be used to prevent sample size imbalance between groups and control for&#xD;
      important covariates (e.g. age, comorbidities, gender) that may affect trial results.&#xD;
      Participants in the intervention group will receive 1000 mg nitazoxanide (two tablets of 500&#xD;
      mg each) with meal two times daily (8 am and 8 pm) and one tablet of 300/100 mg&#xD;
      atazanavir/ritonavir with meal once daily (8 pm) in addition SOC. Participants in the control&#xD;
      arm will receive the SOC alone. SOC will be as determined by the clinical team at the&#xD;
      treatment centres in line with the current National Interim Guidelines for Clinical&#xD;
      Management of COVID-19.&#xD;
&#xD;
      The treatment duration for participants in the intervention group will be 14 days. However,&#xD;
      follow up will continue until day 28 after study entry at the end of which all participants&#xD;
      will exit the study. Evaluations at follow up visits will include daily symptoms monitoring&#xD;
      using inFLUenza Patient-Reported Outcome (FLU-PRO) questionnaire, daily vitals, daily&#xD;
      clinical improvement assessment, and swab and/or sputum collection for SARS-CoV-2 on days 2,&#xD;
      4, 6, 7, 14, and 28.&#xD;
&#xD;
      Sample size estimation is based on the assumption that an improvement of at least 60-80% in&#xD;
      time to SARS-CoV-2 PCR negativity and symptoms resolution can be achieved in the intervention&#xD;
      group compared with the control group. Hence, a total sample size of 89 will provide at least&#xD;
      80% power to show or exclude 60% improvement in time to SARS-CoV-2 PCR negativity. This&#xD;
      assumes a two-sided and 5% type 1 error rate. Therefore, providing for a 10% loss to follow&#xD;
      up rate, a total of 98 patients will be recruited.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    IDSMB recommendation&#xD;
  </why_stopped>
  <start_date type="Actual">October 9, 2020</start_date>
  <completion_date type="Actual">May 2, 2021</completion_date>
  <primary_completion_date type="Actual">May 2, 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to clinical improvement</measure>
    <time_frame>28 days</time_frame>
    <description>Proportion of patients with clinical improvement, as defined by live discharge from the hospital, a decrease of at least 2 points from baseline on a 7-point ordinal scale, or both.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to SARS-CoV-2 negativity</measure>
    <time_frame>28 days</time_frame>
    <description>Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result at Days 7, 10, 14 and 28</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in SARS-CoV-2 AUC</measure>
    <time_frame>28 days</time_frame>
    <description>Temporal patterns of SARS-CoV-2 viral load quantified by RT-PCR from nasal swabs or sputum of patients receiving SOC alone versus SOC plus study drug</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to symptoms resolution</measure>
    <time_frame>28 days</time_frame>
    <description>Time to symptoms resolution as monitored by the Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) questionnaire with some modifications for COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical status as assessed with the seven-category ordinal scale on days 7 and 14</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospitalization in survivors</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Day 28 mortality</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from treatment initiation to death</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion with viral RNA detection over time</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Covid-19</condition>
  <arm_group>
    <arm_group_label>Standard of Care (SOC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in this arm will receive SOC alone, which will be as determined by the clinical team at the treatment centres in line with the current National Interim Guidelines for Clinical Management of COVID-19</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SOC plus Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm will receive SOC plus study intervention composed of orally administered nitazoxanide and atazanavir/ritonavir tablets</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nitazoxanide and atazanavir/ritonavir</intervention_name>
    <description>1000 mg nitazoxanide tablets twice daily and 300/100 mg atazanavir/ritonavir tablets once daily with meal</description>
    <arm_group_label>SOC plus Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>SOC will be as determined by the clinical team at the treatment centres in line with the current National Interim Guidelines for Clinical Management of COVID-19</description>
    <arm_group_label>SOC plus Intervention</arm_group_label>
    <arm_group_label>Standard of Care (SOC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willingness and ability to provide written informed consent&#xD;
&#xD;
          -  At least 18 and not more than 75 years of age at study entry&#xD;
&#xD;
          -  SARS-CoV-2 infection confirmed by PCR test within 4 days before randomization&#xD;
&#xD;
          -  Currently symptomatic (fever or chills, cough, myalgia, sore throat, shortness of&#xD;
             breath, or new onset of anosmia or ageusia) and at COVID-19 isolation and treatment&#xD;
             centre&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to take orally administered medication or food&#xD;
&#xD;
          -  Known hypersensitivity to study medication&#xD;
&#xD;
          -  Pregnant or lactating (unless practicing exclusive replacement feeding for the entire&#xD;
             study duration)&#xD;
&#xD;
          -  Participation in any other interventional trial for COVID-19 (observational study&#xD;
             co-enrollment allowed)&#xD;
&#xD;
          -  Concurrent treatment with other agents with actual or possible direct-acting antiviral&#xD;
             activity against SARS-CoV-2 less than 24 hours prior to study drug dosing&#xD;
&#xD;
          -  Concurrent use of agents with known or uncertain interaction with study drugs,&#xD;
             including ritonavir&#xD;
&#xD;
          -  Requiring mechanical ventilation at screening&#xD;
&#xD;
          -  Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) above 5 times upper&#xD;
             limit of normal (ULN)&#xD;
&#xD;
          -  Creatinine clearance below 50 mL/min using the Cockcroft-Gault formula for&#xD;
             participants above 18 years of age&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Olabisi Onabanjo University Teaching Hospital</name>
      <address>
        <city>Sagamu</city>
        <state>Ogun State</state>
        <country>Nigeria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Infectious Disease Hospital, Olodo</name>
      <address>
        <city>Ibadan</city>
        <state>Oyo State</state>
        <country>Nigeria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Nigeria</country>
  </location_countries>
  <link>
    <url>https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021497s001,021498s004lbl.pdf</url>
    <description>Nitaxoxanide Prescribing Information</description>
  </link>
  <link>
    <url>https://www.biorxiv.org/content/10.1101/2020.04.04.020925v2</url>
    <description>Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production</description>
  </link>
  <link>
    <url>https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf</url>
    <description>Atazanavir/ritonavir Prescribing Information</description>
  </link>
  <reference>
    <citation>Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health. 2016 May-Jun;9(3):227-30. doi: 10.1016/j.jiph.2016.04.001. Epub 2016 Apr 16.</citation>
    <PMID>27095301</PMID>
  </reference>
  <reference>
    <citation>Cao J, Forrest JC, Zhang X. A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs. Antiviral Res. 2015 Feb;114:1-10. doi: 10.1016/j.antiviral.2014.11.010. Epub 2014 Nov 28.</citation>
    <PMID>25451075</PMID>
  </reference>
  <reference>
    <citation>Haffizulla J, Hartman A, Hoppers M, Resnick H, Samudrala S, Ginocchio C, Bardin M, Rossignol JF; US Nitazoxanide Influenza Clinical Study Group. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial. Lancet Infect Dis. 2014 Jul;14(7):609-18. doi: 10.1016/S1473-3099(14)70717-0. Epub 2014 May 19.</citation>
    <PMID>24852376</PMID>
  </reference>
  <reference>
    <citation>Arshad U, Pertinez H, Box H, Tatham L, Rajoli RKR, Curley P, Neary M, Sharp J, Liptrott NJ, Valentijn A, David C, Rannard SP, O'Neill PM, Aljayyoussi G, Pennington SH, Ward SA, Hill A, Back DJ, Khoo SH, Bray PG, Biagini GA, Owen A. Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics. Clin Pharmacol Ther. 2020 Oct;108(4):775-790. doi: 10.1002/cpt.1909. Epub 2020 Jun 14. Erratum In: Clin Pharmacol Ther. 2021 May;109(5):1362.</citation>
    <PMID>32438446</PMID>
  </reference>
  <reference>
    <citation>Rajoli RK, Pertinez H, Arshad U, Box H, Tatham L, Curley P, Neary M, Sharp J, Liptrott NJ, Valentijn A, David C, Rannard SP, Aljayyoussi G, Pennington SH, Hill A, Boffito M, Ward SA, Khoo SH, Bray PG, O'Neill PM, Hong WD, Biagini G, Owen A. Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis. medRxiv. 2020 May 6:2020.05.01.20087130. doi: 10.1101/2020.05.01.20087130. Preprint.</citation>
    <PMID>32511548</PMID>
  </reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>February 14, 2022</last_update_submitted>
  <last_update_submitted_qc>February 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SARS-CoV infection</keyword>
  <keyword>COVID-19</keyword>
  <keyword>coronavirus</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>Ritonavir</mesh_term>
    <mesh_term>Atazanavir Sulfate</mesh_term>
    <mesh_term>Nitazoxanide</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/NCT04459286
org study id: NACOVID
nct id: NCT04459286
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Since the outbreak of the novel coronavirus disease in 2019 (COVID-19), an unprecedented
      global search for potential therapeutics and vaccines is ongoing. In this study, a
      combination of two drugs that have been shown to be effective against the germ that causes
      COVID-19 in the laboratory will be tested in patients diagnosed with moderate to severe
      COVID-19. One of the drugs is called nitazoxanide and the second is atazanavir/ritonavir.
      Nitazoxanide has been used for the treatment of diarrhea since 2004 while
      atazanavir/ritonavir was approved for HIV treatment in 2003. They are known to be safe in
      humans.

      In this pilot study, 98 COVID-19 patients will be recruited into two groups. The 49 patients
      in group 1 will receive the standard of care determined by their primary care providers while
      the 49 patients in group 2 will receive both the standard of care combined with the two study
      drugs. Patients in group 2 will receive the study drugs for 14 days and all patients will be
      monitored for a total of 28 days.

      The time it takes for the germ that causes COVID-19 to be completely removed from the body
      (in nasal secretions) and the time to clinical improvement will be monitored in all patients
      and compared between the two groups.
COVID-19 caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) is an
      unprecedented global public health challenge which as at July 1, 2020 has spread to over 210
      countries with over 10.6 million cases resulting in 514,808 deaths. More than 1500 clinical
      trials are currently ongoing in an unprecedented global search for potential therapeutics and
      vaccines. With increasing number of cases reported in low- and middle-income countries and
      and the possibility of a second wave of infections in countries where the pandemic appears to
      have slowed, studies to investigate promising therapies are urgently needed, especially those
      that can significantly reduce time to viral clearance and mortality. Shortening SARS-CoV-2
      clearance time will lower treatment cost and reduce the economic impact of the pandemic.

      The purpose of this phase 2 trial is to investigate the efficacy and safety of repurposed
      antiprotozoal and antiretroviral drugs, nitazoxanide and atazanavir/ritonavir, in achievement
      of SARS-CoV-2 PCR negativity and shorten the time to clinical improvement in patients
      diagnosed with moderate to severe COVID-19. The selection of candidates for this COVID-19
      drug repurposing trial was guided by three pharmacological considerations: (1) demonstration
      of in-vitro anti-SARS-CoV-2 activity at doses shown or predicted to be tolerated by humans,
      (2) the feasibility of achieving effective concentration in relevant compartments, and (3)
      established human safety record.

      This is a pilot phase 2, open label randomized controlled trial. A total of 98 patients with
      confirmed COVID-19 diagnosis (defined as SARS-CoV-2 polymerase chain reaction (PCR) positive
      nasopharyngeal swab) will be recruited from participating treatment centres. Participants
      will be randomised to receive either the standard of care (SOC) plus nitazoxanide for 14
      days, starting from day 1 or the SOC alone for 14 days.

      Participants will be recruited within 2 days of admission into COVID-19 treatment centre.
      Before enrollment, they will be given adequate information about the trial, opportunity to
      ask questions, and sufficient time to consider participation. Before any screening
      procedures, a written consent will be obtained from each eligible subject who agrees to
      participate in the trial. Participants will then be randomly allocated 1:1 to receive either
      the SOC alone (control group) or SOC plus study drug (intervention group). Parallel
      assignment will be used to prevent sample size imbalance between groups and control for
      important covariates (e.g. age, comorbidities, gender) that may affect trial results.
      Participants in the intervention group will receive 1000 mg nitazoxanide (two tablets of 500
      mg each) with meal two times daily (8 am and 8 pm) and one tablet of 300/100 mg
      atazanavir/ritonavir with meal once daily (8 pm) in addition SOC. Participants in the control
      arm will receive the SOC alone. SOC will be as determined by the clinical team at the
      treatment centres in line with the current National Interim Guidelines for Clinical
      Management of COVID-19.

      The treatment duration for participants in the intervention group will be 14 days. However,
      follow up will continue until day 28 after study entry at the end of which all participants
      will exit the study. Evaluations at follow up visits will include daily symptoms monitoring
      using inFLUenza Patient-Reported Outcome (FLU-PRO) questionnaire, daily vitals, daily
      clinical improvement assessment, and swab and/or sputum collection for SARS-CoV-2 on days 2,
      4, 6, 7, 14, and 28.

      Sample size estimation is based on the assumption that an improvement of at least 60-80% in
      time to SARS-CoV-2 PCR negativity and symptoms resolution can be achieved in the intervention
      group compared with the control group. Hence, a total sample size of 89 will provide at least
      80% power to show or exclude 60% improvement in time to SARS-CoV-2 PCR negativity. This
      assumes a two-sided and 5% type 1 error rate. Therefore, providing for a 10% loss to follow
      up rate, a total of 98 patients will be recruited.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Time to clinical improvement
time frame: 28 days
description: Proportion of patients with clinical improvement, as defined by live discharge from the hospital, a decrease of at least 2 points from baseline on a 7-point ordinal scale, or both.
measure: Time to SARS-CoV-2 negativity
time frame: 28 days
description: Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result at Days 7, 10, 14 and 28
measure: Difference in SARS-CoV-2 AUC
time frame: 28 days
description: Temporal patterns of SARS-CoV-2 viral load quantified by RT-PCR from nasal swabs or sputum of patients receiving SOC alone versus SOC plus study drug
measure: Time to symptoms resolution
time frame: 28 days
description: Time to symptoms resolution as monitored by the Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) questionnaire with some modifications for COVID-19
measure: Clinical status as assessed with the seven-category ordinal scale on days 7 and 14
time frame: 14 days
measure: Duration of hospitalization in survivors
time frame: 28 days
measure: Day 28 mortality
time frame: 28 days
measure: Time from treatment initiation to death
time frame: 28 days
measure: Proportion with viral RNA detection over time
time frame: 28 days
arm group label: Standard of Care (SOC)
arm group type: Active Comparator
description: Participants in this arm will receive SOC alone, which will be as determined by the clinical team at the treatment centres in line with the current National Interim Guidelines for Clinical Management of COVID-19
arm group label: SOC plus Intervention
arm group type: Experimental
description: Participants in this arm will receive SOC plus study intervention composed of orally administered nitazoxanide and atazanavir/ritonavir tablets
intervention type: Drug
intervention name: Nitazoxanide and atazanavir/ritonavir
description: 1000 mg nitazoxanide tablets twice daily and 300/100 mg atazanavir/ritonavir tablets once daily with meal
arm group label: SOC plus Intervention
intervention type: Other
intervention name: Standard of Care
description: SOC will be as determined by the clinical team at the treatment centres in line with the current National Interim Guidelines for Clinical Management of COVID-19
arm group label: SOC plus Intervention
arm group label: Standard of Care (SOC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
facility: 
country: Nigeria
url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021497s001,021498s004lbl.pdf
description: Nitaxoxanide Prescribing Information
url: https://www.biorxiv.org/content/10.1101/2020.04.04.020925v2
description: Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production
url: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf
description: Atazanavir/ritonavir Prescribing Information
citation: Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health. 2016 May-Jun;9(3):227-30. doi: 10.1016/j.jiph.2016.04.001. Epub 2016 Apr 16.
PMID: 27095301
citation: Cao J, Forrest JC, Zhang X. A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs. Antiviral Res. 2015 Feb;114:1-10. doi: 10.1016/j.antiviral.2014.11.010. Epub 2014 Nov 28.
PMID: 25451075
citation: Haffizulla J, Hartman A, Hoppers M, Resnick H, Samudrala S, Ginocchio C, Bardin M, Rossignol JF; US Nitazoxanide Influenza Clinical Study Group. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial. Lancet Infect Dis. 2014 Jul;14(7):609-18. doi: 10.1016/S1473-3099(14)70717-0. Epub 2014 May 19.
PMID: 24852376
citation: Arshad U, Pertinez H, Box H, Tatham L, Rajoli RKR, Curley P, Neary M, Sharp J, Liptrott NJ, Valentijn A, David C, Rannard SP, O'Neill PM, Aljayyoussi G, Pennington SH, Ward SA, Hill A, Back DJ, Khoo SH, Bray PG, Biagini GA, Owen A. Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics. Clin Pharmacol Ther. 2020 Oct;108(4):775-790. doi: 10.1002/cpt.1909. Epub 2020 Jun 14. Erratum In: Clin Pharmacol Ther. 2021 May;109(5):1362.
PMID: 32438446
citation: Rajoli RK, Pertinez H, Arshad U, Box H, Tatham L, Curley P, Neary M, Sharp J, Liptrott NJ, Valentijn A, David C, Rannard SP, Aljayyoussi G, Pennington SH, Hill A, Boffito M, Ward SA, Khoo SH, Bray PG, O'Neill PM, Hong WD, Biagini G, Owen A. Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis. medRxiv. 2020 May 6:2020.05.01.20087130. doi: 10.1101/2020.05.01.20087130. Preprint.
PMID: 32511548
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Ritonavir
mesh term: Atazanavir Sulfate
mesh term: Nitazoxanide
sharing ipd: No