<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/NCT04432987</url>
  </required_header>
  <id_info>
    <org_study_id>8820</org_study_id>
    <nct_id>NCT04432987</nct_id>
  </id_info>
  <brief_title>Dornase Alpha for the Treatment of COVID-19</brief_title>
  <official_title>Determination of Dornase Alpha Effectiveness in COVID-19 Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Acibadem University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Scientific and Technological Research Council of Turkey</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Acibadem 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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, the effectiveness of the Dornase Alpha treatment, which is known to reduce the&#xD;
      viscosity of respiratory secretions, will be investigated in new diagnosed and severe&#xD;
      COVID-19 patients separately.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recent studies confirmed the role of immune hyperactivation in the pathogenesis of COVID-19.&#xD;
      Immune cells, especially neutrophils, infiltrate pulmonary capillaries that cause acute&#xD;
      fibrin deposition and extravasation into the alveolar space. This excessive accumulation of&#xD;
      neutrophils constitutes NETs which makes the mucus thick and viscous. The highly viscous&#xD;
      mucus lowers the patient's respiratory function and impairs ventilation supporting NETs may&#xD;
      play a major role in the disease. As a mechanism, double-stranded DNA constitutes the&#xD;
      backbone of NETs and Dornase alfa promotes the clearance of NETs from plasma neutralization.&#xD;
      Endogenous Deoxyribonucleases (DNases), which physiologically break up this extracellular&#xD;
      DNA, may become overwhelmed by a massive influx of NETs. Clinically, recombinant human DNase&#xD;
      I (rhDNase, Dornase Alfa) has the identical primary amino acid sequence with the native human&#xD;
      enzyme and has been approved for the management of cystic fibrosis. Daily administration of&#xD;
      dornase alfa is effective in the treatment of cystic fibrosis patients improving pulmonary&#xD;
      functions. The similarity of mucus secretions in COVID-19 and cystic fibrosis patients by the&#xD;
      means of NETs makes Dornase alfa as a therapeutic option in COVID-19.&#xD;
&#xD;
      Progressive COVID-19 pneumonia may be mortal if it is not treated early, causing respiratory&#xD;
      failure. The most important factor leading to respiratory failure is hyaline membrane formed&#xD;
      by a neutrophil trap that develops in the cavities of the alveoli. Dornase Alpha is thought&#xD;
      to have an important contribution by the lysis of this hyalen membrane. In this study, it is&#xD;
      aimed to evaluate the effectiveness of Dornase Alpha treatment in case of early and late use&#xD;
      in COVID-19 disease.&#xD;
&#xD;
      Patients diagnosed with COVID-19 PCR and / or radiological-clinical findings is included in&#xD;
      the study, and this treatment is carried out in 2 patient groups in comparison with the&#xD;
      control groups. The groups are:&#xD;
&#xD;
        1. Newly Diagnosed Patient Group I. Dornase Alpha treated group ii. Control group&#xD;
&#xD;
        2. Patient Group Monitored by Mechanical Ventilation I. Dornase Alpha treated group ii.&#xD;
           Control group&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 25, 2020</start_date>
  <completion_date type="Anticipated">September 25, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 25, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response</measure>
    <time_frame>3 months</time_frame>
    <description>i. The patient has no complaints (cough and dyspnea completely disappear, the number of breaths are in the age-appropriate range, oxygen saturation is in the normal range), inflammatory markers in blood improve (CRP, LDH, Ferritin and D-Dimer regression to the reference range).&#xD;
ii. Extubation (for mechanically ventilated group)&#xD;
iii. Intubated (for newly diagnosed group)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>3 months</time_frame>
    <description>Death</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Newly Diagnosed Patient Group (n=30)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>I. Dornase Alpha treated group (n=15)&#xD;
ii. Control group (n=15)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patient Group Monitored by Mechanical Ventilation (n=30)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>I. Dornase Alpha treated group (n=15)&#xD;
ii. Control group (n=15)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pulmozyme</intervention_name>
    <description>PULMOZYME contains an active substance called dornase alpha as an active substance. Dornase alpha is a human-made version of a protein called DNase in your body and is also known as recombinant human deoxyribonuclease 1 or rhDNase.&#xD;
Drug will be administered at a dose of 2,5 mg/2 times per day for 7 days</description>
    <arm_group_label>Newly Diagnosed Patient Group (n=30)</arm_group_label>
    <arm_group_label>Patient Group Monitored by Mechanical Ventilation (n=30)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Being 18 or older&#xD;
&#xD;
          -  Approving the Informed Consent Form&#xD;
&#xD;
          -  Being diagnosed with COVID-19 with PCR and / or radiological clinical findings&#xD;
&#xD;
          -  Hospitalization indication according to Ministry of Health criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant and / or breastfeeding women.&#xD;
&#xD;
          -  Any known allergy to Dornase Alpha&#xD;
&#xD;
          -  Being involved in another drug study&#xD;
&#xD;
          -  Previously diagnosed with chronic lung disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ercument Ovalı, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Acıbadem Labcell Cellular Therapy Laboratories</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ercument Ovalı, MD</last_name>
    <phone>+905325729174</phone>
    <email>ercument.ovali@acibadem.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Acıbadem Altunizade Hospital</name>
      <address>
        <city>Istanbul</city>
        <zip>34662</zip>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ercument Ovalı, Prof.</last_name>
      <phone>+905325729174</phone>
      <email>ercument.ovali@acibademlabcell.com.tr</email>
    </contact>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>June 15, 2020</last_update_submitted>
  <last_update_submitted_qc>June 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19, Dornase Alpha</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_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/NCT04432987
org study id: 8820
nct id: NCT04432987
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
In this study, the effectiveness of the Dornase Alpha treatment, which is known to reduce the
      viscosity of respiratory secretions, will be investigated in new diagnosed and severe
      COVID-19 patients separately.
Recent studies confirmed the role of immune hyperactivation in the pathogenesis of COVID-19.
      Immune cells, especially neutrophils, infiltrate pulmonary capillaries that cause acute
      fibrin deposition and extravasation into the alveolar space. This excessive accumulation of
      neutrophils constitutes NETs which makes the mucus thick and viscous. The highly viscous
      mucus lowers the patient's respiratory function and impairs ventilation supporting NETs may
      play a major role in the disease. As a mechanism, double-stranded DNA constitutes the
      backbone of NETs and Dornase alfa promotes the clearance of NETs from plasma neutralization.
      Endogenous Deoxyribonucleases (DNases), which physiologically break up this extracellular
      DNA, may become overwhelmed by a massive influx of NETs. Clinically, recombinant human DNase
      I (rhDNase, Dornase Alfa) has the identical primary amino acid sequence with the native human
      enzyme and has been approved for the management of cystic fibrosis. Daily administration of
      dornase alfa is effective in the treatment of cystic fibrosis patients improving pulmonary
      functions. The similarity of mucus secretions in COVID-19 and cystic fibrosis patients by the
      means of NETs makes Dornase alfa as a therapeutic option in COVID-19.

      Progressive COVID-19 pneumonia may be mortal if it is not treated early, causing respiratory
      failure. The most important factor leading to respiratory failure is hyaline membrane formed
      by a neutrophil trap that develops in the cavities of the alveoli. Dornase Alpha is thought
      to have an important contribution by the lysis of this hyalen membrane. In this study, it is
      aimed to evaluate the effectiveness of Dornase Alpha treatment in case of early and late use
      in COVID-19 disease.

      Patients diagnosed with COVID-19 PCR and / or radiological-clinical findings is included in
      the study, and this treatment is carried out in 2 patient groups in comparison with the
      control groups. The groups are:

        1. Newly Diagnosed Patient Group I. Dornase Alpha treated group ii. Control group

        2. Patient Group Monitored by Mechanical Ventilation I. Dornase Alpha treated group ii.
           Control group
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response
time frame: 3 months
description: i. The patient has no complaints (cough and dyspnea completely disappear, the number of breaths are in the age-appropriate range, oxygen saturation is in the normal range), inflammatory markers in blood improve (CRP, LDH, Ferritin and D-Dimer regression to the reference range).
ii. Extubation (for mechanically ventilated group)
iii. Intubated (for newly diagnosed group)
measure: Survival
time frame: 3 months
description: Death
arm group label: Newly Diagnosed Patient Group (n=30)
arm group type: Experimental
description: I. Dornase Alpha treated group (n=15)
ii. Control group (n=15)
arm group label: Patient Group Monitored by Mechanical Ventilation (n=30)
arm group type: Experimental
description: I. Dornase Alpha treated group (n=15)
ii. Control group (n=15)
intervention type: Drug
intervention name: Pulmozyme
description: PULMOZYME contains an active substance called dornase alpha as an active substance. Dornase alpha is a human-made version of a protein called DNase in your body and is also known as recombinant human deoxyribonuclease 1 or rhDNase.
Drug will be administered at a dose of 2,5 mg/2 times per day for 7 days
arm group label: Newly Diagnosed Patient Group (n=30)
arm group label: Patient Group Monitored by Mechanical Ventilation (n=30)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ercument Ovalı, MD
role: Principal Investigator
affiliation: Acıbadem Labcell Cellular Therapy Laboratories
last name: Ercument Ovalı, MD
phone: +905325729174
email: ercument.ovali@acibadem.com
facility: 
status: Recruiting
contact: 
country: Turkey
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No