<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/NCT04477083</url>
  </required_header>
  <id_info>
    <org_study_id>inhalable HCQ</org_study_id>
    <nct_id>NCT04477083</nct_id>
  </id_info>
  <brief_title>Development and Validation of &quot;Ready-to-Use&quot; Inhalable Forms of Hydroxychloroquine for Treatment of COVID-19</brief_title>
  <official_title>Development and Validation of &quot;Ready-to-Use&quot; Inhalable Forms of Hydroxychloroquine for Treatment of COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mansoura University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mansoura University</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this project, we aimed at developing new &quot;Ready-to-Use&quot; inhalable forms of HCQ that can be&#xD;
      used directly through nebulization or using dry powder inhalers (DPIs). These inhaled forms&#xD;
      would allow a simple and direct delivery of the drug (HCQ) specifically towards the throat&#xD;
      and the lung which are the main sites for the COVID-19 viral infection. Hence, the drug can&#xD;
      be available at higher concentrations in the throat and lungs as compared with the currently&#xD;
      used treatment protocols, while minimizing the drug systemic concentrations and its presence&#xD;
      in other body organs, and thus enhancing the drug efficacy with significantly limiting its&#xD;
      side effects. Besides, using inhalable forms can be more convenient to patients suffering&#xD;
      from gastrointestinal complications from the disease that can limit the absorption of oral&#xD;
      forms. Moreover, the proposed inhalable forms are designed in such a way to hide the drug&#xD;
      from the immune system (confer stealth characteristics) using FDA-approved excipients to&#xD;
      minimize/avoid any immune response towards the drug as was noted towards it in its oral form&#xD;
      that's used in the treatment protocol of COVID-19. In addition, the inhaled formulations will&#xD;
      be designed to maintain the overall simplicity and scalability of the preparation which is&#xD;
      critical during this urgent pandemic situation. The cost of the final formulation is also&#xD;
      taken into consideration since the drug is intended for treatment of thousands or probably&#xD;
      millions of patients around the world including countries with limited economic capabilities.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">July 15, 2020</start_date>
  <completion_date type="Anticipated">August 15, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 15, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>The first 20 consecutive patients (group A) will be treated by oral antibiotics, supportive treatment and inhalable hydroxychloroquine (HCQ). (In day 1, an inhaled hydroxychloroquine sulfate dose of 12 mg will be taken via nebulization three times/day (TID) as a loading dose. Then, starting from day 2, same dose of 12 mg of inhaled hydroxychloroquine will be taken twice/day (BID) as maintenance dose for 5 days. The subsequent 20 consecutive patients (group B) will receive the same treatment of group A but without inhalable hydroxychloroquine (HCQ). At day 7, all patients of both groups will be evaluated by clinical, laboratory and chest CT parameters. Patients of group B who still show no clinical, laboratory or radiological improvement will continue treatment by adding inhalable hydroxychloroquine (HCQ). for another 7 days and re-evaluated at day 14. Patients of group A who still show no significant improvement at day 7 only will be re-checked at day 14.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to clinical recovery defined as 3 days afebrile with improved cough and other clinical signs</measure>
    <time_frame>15 days</time_frame>
    <description>Time is measured in hours</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to achieve viral clearance state determined by two successive negative PCR results for two oropharyngeal swabs separated by 48 hours.</measure>
    <time_frame>15 days</time_frame>
    <description>Time is measured in hours</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>15 days</time_frame>
    <description>measuring and monitoring the complication between groups</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Covid19</condition>
  <condition>Hydroxychloroquine Adverse Reaction</condition>
  <arm_group>
    <arm_group_label>inhalable hydroxychloroquine (HCQ).</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>supportive and symptomatic treatment and inhalable hydroxychloroquine (HCQ).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>supportive and symptomatic treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>inhalable hydroxychloroquine (HCQ)</intervention_name>
    <description>inhalable hydroxychloroquine (HCQ) plus supportive and symptomatic treatment</description>
    <arm_group_label>inhalable hydroxychloroquine (HCQ).</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>supportive and symptomatic treatment</intervention_name>
    <description>supportive and symptomatic treatment</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 year&#xD;
&#xD;
          -  Laboratory (RT-PCR) positive of SARS-COV-2 (Moderate cases)&#xD;
&#xD;
          -  Chest CT with pneumonia.&#xD;
&#xD;
          -  SaO2/SPO2 ratio &gt; 93% or PaO2/FIO2 ratio &gt; 300 mmHg under the condition in the&#xD;
             hospital room.&#xD;
&#xD;
          -  Welling to participate and able to give fully informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe and critical illness.&#xD;
&#xD;
          -  Retinopathy and other retinal diseases.&#xD;
&#xD;
          -  Arrhythmias.&#xD;
&#xD;
          -  QT ≥ 400 msec&#xD;
&#xD;
          -  Receiving cardiac drugs&#xD;
&#xD;
          -  Severe liver disease.&#xD;
&#xD;
          -  Pregnancy or lactation.&#xD;
&#xD;
          -  Previous treatment of COVID-19.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Mansoura University Hospital</name>
      <address>
        <city>Mansoura</city>
        <state>Outside U.S./Canada</state>
        <zip>35516</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>July 17, 2020</last_update_submitted>
  <last_update_submitted_qc>July 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mansoura University</investigator_affiliation>
    <investigator_full_name>Ibrahim M. El-Sherbiny</investigator_full_name>
    <investigator_title>PHD</investigator_title>
  </responsible_party>
  <keyword>Covid19</keyword>
  <keyword>Hydroxychloroquine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04477083
org study id: inhalable HCQ
nct id: NCT04477083
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this project, we aimed at developing new "Ready-to-Use" inhalable forms of HCQ that can be
      used directly through nebulization or using dry powder inhalers (DPIs). These inhaled forms
      would allow a simple and direct delivery of the drug (HCQ) specifically towards the throat
      and the lung which are the main sites for the COVID-19 viral infection. Hence, the drug can
      be available at higher concentrations in the throat and lungs as compared with the currently
      used treatment protocols, while minimizing the drug systemic concentrations and its presence
      in other body organs, and thus enhancing the drug efficacy with significantly limiting its
      side effects. Besides, using inhalable forms can be more convenient to patients suffering
      from gastrointestinal complications from the disease that can limit the absorption of oral
      forms. Moreover, the proposed inhalable forms are designed in such a way to hide the drug
      from the immune system (confer stealth characteristics) using FDA-approved excipients to
      minimize/avoid any immune response towards the drug as was noted towards it in its oral form
      that's used in the treatment protocol of COVID-19. In addition, the inhaled formulations will
      be designed to maintain the overall simplicity and scalability of the preparation which is
      critical during this urgent pandemic situation. The cost of the final formulation is also
      taken into consideration since the drug is intended for treatment of thousands or probably
      millions of patients around the world including countries with limited economic capabilities.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The first 20 consecutive patients (group A) will be treated by oral antibiotics, supportive treatment and inhalable hydroxychloroquine (HCQ). (In day 1, an inhaled hydroxychloroquine sulfate dose of 12 mg will be taken via nebulization three times/day (TID) as a loading dose. Then, starting from day 2, same dose of 12 mg of inhaled hydroxychloroquine will be taken twice/day (BID) as maintenance dose for 5 days. The subsequent 20 consecutive patients (group B) will receive the same treatment of group A but without inhalable hydroxychloroquine (HCQ). At day 7, all patients of both groups will be evaluated by clinical, laboratory and chest CT parameters. Patients of group B who still show no clinical, laboratory or radiological improvement will continue treatment by adding inhalable hydroxychloroquine (HCQ). for another 7 days and re-evaluated at day 14. Patients of group A who still show no significant improvement at day 7 only will be re-checked at day 14.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Time to clinical recovery defined as 3 days afebrile with improved cough and other clinical signs
time frame: 15 days
description: Time is measured in hours
measure: Time to achieve viral clearance state determined by two successive negative PCR results for two oropharyngeal swabs separated by 48 hours.
time frame: 15 days
description: Time is measured in hours
measure: Incidence of Treatment-Emergent Adverse Events
time frame: 15 days
description: measuring and monitoring the complication between groups
arm group label: inhalable hydroxychloroquine (HCQ).
arm group type: Active Comparator
description: supportive and symptomatic treatment and inhalable hydroxychloroquine (HCQ).
arm group label: Placebo
arm group type: Placebo Comparator
description: supportive and symptomatic treatment
intervention type: Drug
intervention name: inhalable hydroxychloroquine (HCQ)
description: inhalable hydroxychloroquine (HCQ) plus supportive and symptomatic treatment
arm group label: inhalable hydroxychloroquine (HCQ).
intervention type: Drug
intervention name: supportive and symptomatic treatment
description: supportive and symptomatic treatment
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Mansoura University
investigator full name: Ibrahim M. El-Sherbiny
investigator title: PHD
mesh term: COVID-19
mesh term: Hydroxychloroquine