<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/NCT04405921</url>
  </required_header>
  <id_info>
    <org_study_id>PACTT</org_study_id>
    <nct_id>NCT04405921</nct_id>
  </id_info>
  <brief_title>Hydroxychloroquine, Azithromycin in the Treatment of Covid-19</brief_title>
  <acronym>PACTT</acronym>
  <official_title>Hydroxychloroquine, Azithromycin in the Treatment of Covid-19 Pneumonia: A Randomized,Open-label,Controlled Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hôpital Universitaire Farhat Hached</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hôpital Universitaire Farhat Hached</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>
      This study investigates the efficay and tolerance of 5-days course of hydroxychloroquine or&#xD;
      hydroxychloroquine and azithromycin of patients with COVID-19 infection. The investigators&#xD;
      will undertake a randomized, double-blind, controlled Trial in the region of Sousse Tunisia&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is a critical need to identify effective treatments and a number of molecules have been&#xD;
      suggested, but The investigators still do not have enough evidence about their efficacy, to&#xD;
      treat COVID-19 pneumonia.&#xD;
&#xD;
      One of the most tested treatments was the use of Chloroquine or Hydroxychloroquine associated&#xD;
      or not to azithromycin.&#xD;
&#xD;
      Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. It's&#xD;
      known to block virus infection by increasing endosomal pH required for virus/cell fusion, as&#xD;
      well as interfering with the glycosylation of cellular receptors of SARS-CoV. It's also&#xD;
      demonstrated that CQ functioned at both entry, and at postentry stages of the 2019-nCoV&#xD;
      infection in Vero E6 cells. Besides its antiviral activity, CQ has an immune-modulating&#xD;
      activity, which may synergistically enhance its antiviral effect in vivo.&#xD;
&#xD;
      However, evidence regarding its effects in patients is limited. Among patients with COVID-19,&#xD;
      the use of Hydroxychloroquine (HCQ) could significantly shorten time to clinical recovery&#xD;
      (TTCR) and promote the absorption of pneumonia. This result has been presented in a&#xD;
      randomized controlled trial using two arms HCQ versus conventional treatment. The beneficial&#xD;
      effect of HCQ has been proven among mild severity COVID-19 pneumonia but the sample size of&#xD;
      this study was limited to 31 patients in each group.&#xD;
&#xD;
      Gautret et al also reported that HCQ treatment is significantly associated with viral load&#xD;
      reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. A&#xD;
      study showed that azithromycin concentration in phagocytic cells is 40× to 150× higher than&#xD;
      plasma concentrations. However, Gautret study has many limitations including selection biases&#xD;
      because of non-randomization, a small sample size, and dropout of six patients from the&#xD;
      study.&#xD;
&#xD;
      In terms of treatment duration, there is no study supporting a long course treatment of 10&#xD;
      days versus a short course treatment of 5 days for HCQ. This treatment is known to have a&#xD;
      large distribution volume of 73 l/kg and a plasma half life going from 22 days to 123 days.&#xD;
      This suggests that a short course treatment of Hydroxychloroquine and/or azithromycin could&#xD;
      be as effective as a long course treatment.&#xD;
&#xD;
      On the other hand, there are currently no effective specific antivirals or drug combinations&#xD;
      supported by high-level evidence, and The investigators don't know if HCQ could be effective&#xD;
      or if it's effectiveness may be improved if it's associated with Azithromycin. In fact, this&#xD;
      association can lead to improve pneumonia but can also increase the risk of treatment side&#xD;
      effects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 2020</start_date>
  <completion_date type="Anticipated">March 2021</completion_date>
  <primary_completion_date type="Anticipated">December 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical recovery at day-14, from the start of treatment.</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical recovery is defined as a complete resolution clinical signs appeared during the medical history and related to COVID-19.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Viral Clearance via RT-PCR at day 5- 7-10 and day 14</measure>
    <time_frame>5- 7-10 and day 14</time_frame>
    <description>RT-PCR will be realized in same laboratory</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>SARS-CoV-2 Pneumonia</condition>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Hydroxychloroquine associated to azithromycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hydroxychloroquine: 200 mg twice a day orally or via gastric tube (total 400 mg/day) for 5 days. Azithromycin: 500 mg at day 1 then 250 mg/day for 4 days. with standard of care in association to treatments.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hydroxychloroquine with placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Hydroxychloroquine: 200 mg twice a day orally or via gastric tube (total 400 mg/day) for 5 days. with standard of care in association to treatments.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine 200 Mg Oral Tablet</intervention_name>
    <description>orally or via gastric tube</description>
    <arm_group_label>Hydroxychloroquine associated to azithromycin</arm_group_label>
    <arm_group_label>Hydroxychloroquine with placebo</arm_group_label>
    <other_name>Plaquenil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azithromycin 250 MG</intervention_name>
    <description>orally or via gastric tube</description>
    <arm_group_label>Hydroxychloroquine associated to azithromycin</arm_group_label>
    <other_name>Azro 250</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  PositiveSARS-COV-2 RT-PCR in hospitalized patients in University Hospital Farhat&#xD;
             Hached in Sousse Tunisia.&#xD;
&#xD;
          -  Had either not received hydroxychloroquine before or had received hydroxychloroquine&#xD;
             for at least 1 day and could tolerate a dose of 200 mg of hydroxychloroquine/day.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unableto take oral medication, pregnancy or breast feeding, immune-compromised&#xD;
             patients,&#xD;
&#xD;
          -  Contraindicationto the studied medications&#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_contact>
    <last_name>Amel Letaief, Professor</last_name>
    <phone>21673102501</phone>
    <email>ameletaief@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Hospital Farhat Hached</name>
      <address>
        <city>Sousse</city>
        <zip>4000</zip>
        <country>Tunisia</country>
      </address>
    </facility>
    <contact>
      <last_name>Amel Letaief, Professor</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Tunisia</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>June 18, 2020</last_update_submitted>
  <last_update_submitted_qc>June 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre Hôpital Universitaire Farhat Hached</investigator_affiliation>
    <investigator_full_name>Amel Letaief</investigator_full_name>
    <investigator_title>Professor of infectious diseases</investigator_title>
  </responsible_party>
  <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>Azithromycin</mesh_term>
    <mesh_term>Hydroxychloroquine</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/NCT04405921
org study id: PACTT
nct id: NCT04405921
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study investigates the efficay and tolerance of 5-days course of hydroxychloroquine or
      hydroxychloroquine and azithromycin of patients with COVID-19 infection. The investigators
      will undertake a randomized, double-blind, controlled Trial in the region of Sousse Tunisia
There is a critical need to identify effective treatments and a number of molecules have been
      suggested, but The investigators still do not have enough evidence about their efficacy, to
      treat COVID-19 pneumonia.

      One of the most tested treatments was the use of Chloroquine or Hydroxychloroquine associated
      or not to azithromycin.

      Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. It's
      known to block virus infection by increasing endosomal pH required for virus/cell fusion, as
      well as interfering with the glycosylation of cellular receptors of SARS-CoV. It's also
      demonstrated that CQ functioned at both entry, and at postentry stages of the 2019-nCoV
      infection in Vero E6 cells. Besides its antiviral activity, CQ has an immune-modulating
      activity, which may synergistically enhance its antiviral effect in vivo.

      However, evidence regarding its effects in patients is limited. Among patients with COVID-19,
      the use of Hydroxychloroquine (HCQ) could significantly shorten time to clinical recovery
      (TTCR) and promote the absorption of pneumonia. This result has been presented in a
      randomized controlled trial using two arms HCQ versus conventional treatment. The beneficial
      effect of HCQ has been proven among mild severity COVID-19 pneumonia but the sample size of
      this study was limited to 31 patients in each group.

      Gautret et al also reported that HCQ treatment is significantly associated with viral load
      reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. A
      study showed that azithromycin concentration in phagocytic cells is 40× to 150× higher than
      plasma concentrations. However, Gautret study has many limitations including selection biases
      because of non-randomization, a small sample size, and dropout of six patients from the
      study.

      In terms of treatment duration, there is no study supporting a long course treatment of 10
      days versus a short course treatment of 5 days for HCQ. This treatment is known to have a
      large distribution volume of 73 l/kg and a plasma half life going from 22 days to 123 days.
      This suggests that a short course treatment of Hydroxychloroquine and/or azithromycin could
      be as effective as a long course treatment.

      On the other hand, there are currently no effective specific antivirals or drug combinations
      supported by high-level evidence, and The investigators don't know if HCQ could be effective
      or if it's effectiveness may be improved if it's associated with Azithromycin. In fact, this
      association can lead to improve pneumonia but can also increase the risk of treatment side
      effects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Clinical recovery at day-14, from the start of treatment.
time frame: 14 days
description: Clinical recovery is defined as a complete resolution clinical signs appeared during the medical history and related to COVID-19.
measure: Viral Clearance via RT-PCR at day 5- 7-10 and day 14
time frame: 5- 7-10 and day 14
description: RT-PCR will be realized in same laboratory
arm group label: Hydroxychloroquine associated to azithromycin
arm group type: Experimental
description: Hydroxychloroquine: 200 mg twice a day orally or via gastric tube (total 400 mg/day) for 5 days. Azithromycin: 500 mg at day 1 then 250 mg/day for 4 days. with standard of care in association to treatments.
arm group label: Hydroxychloroquine with placebo
arm group type: Active Comparator
description: Hydroxychloroquine: 200 mg twice a day orally or via gastric tube (total 400 mg/day) for 5 days. with standard of care in association to treatments.
intervention type: Drug
intervention name: Hydroxychloroquine 200 Mg Oral Tablet
description: orally or via gastric tube
arm group label: Hydroxychloroquine associated to azithromycin
arm group label: Hydroxychloroquine with placebo
other name: Plaquenil
intervention type: Drug
intervention name: Azithromycin 250 MG
description: orally or via gastric tube
arm group label: Hydroxychloroquine associated to azithromycin
other name: Azro 250
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Amel Letaief, Professor
phone: 21673102501
email: ameletaief@gmail.com
facility: 
contact: 
country: Tunisia
responsible party type: Principal Investigator
investigator affiliation: Centre Hôpital Universitaire Farhat Hached
investigator full name: Amel Letaief
investigator title: Professor of infectious diseases
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Azithromycin
mesh term: Hydroxychloroquine
sharing ipd: No