<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/NCT04445285</url>
  </required_header>
  <id_info>
    <org_study_id>USAH 1002 000</org_study_id>
    <nct_id>NCT04445285</nct_id>
  </id_info>
  <brief_title>Phase 2 Trial Using rhDNase to Reduce Mortality in COVID-19 Patients With Respiratory Failure</brief_title>
  <acronym>DAMPENCOVID</acronym>
  <official_title>Double Blind Randomized Phase 2 Placebo Controlled Trial Using rhDNase to Reduce Mortality in COVID-19 Patients With Respiratory Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jon Simmons</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of South Alabama</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of South Alabama</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase 2 Randomized Placebo Controlled Trial will determine if administering nebulized&#xD;
      Dornase Alpha (rhDNase) to COVID-19 patients with respiratory failure is safe and will reduce&#xD;
      28-day mortality.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 28, 2020</start_date>
  <completion_date type="Anticipated">February 28, 2022</completion_date>
  <primary_completion_date type="Anticipated">November 30, 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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mortality at 28 days</measure>
    <time_frame>28 days after enrollment</time_frame>
    <description>All Cause Mortality at 28 days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Systemic Therapeutic Response</measure>
    <time_frame>5 days after enrollment</time_frame>
    <description>To assess the effect of Pulmozyme® on the severity of respiratory failure, systemic inflammatory response, and multi-organ failure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Respiratory Response</measure>
    <time_frame>28 days</time_frame>
    <description>Proportion of patients alive and free of invasive mechanical ventilation at 28 days invasive mechanical ventilation at 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Legnth of ICU Stay</measure>
    <time_frame>28 days</time_frame>
    <description>Proportion of patients alive and discharged from the ICU at 28 days discharged from the ICU at 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Legnth of Hospital Stay</measure>
    <time_frame>28 days</time_frame>
    <description>Proportion of patients alive and discharged from the hospital at 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory Response</measure>
    <time_frame>28 days</time_frame>
    <description>Alive, respiratory failure-free days at 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary Function</measure>
    <time_frame>5 days</time_frame>
    <description>Pulmonary Function Ratio at 5 days</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Treatment Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient will receive 2.5mg Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase) aerosolized treatment once every 24 hours for five (5) consecutive days; a total of five (5) doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Arm 0.9% sodium chloride</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patient will receive 2.5ml of Sodium Chloride 0.9% aerosolized treatment once every 24 hours for five (5) consecutive days; a total of five (5) doses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase)</intervention_name>
    <description>2.5mg Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase) aerosolized treatment once every 24 hours for five (5) consecutive days; a total of five (5) doses</description>
    <arm_group_label>Treatment Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.9%sodium chloride</intervention_name>
    <description>Placebo of 0.9% sodium chloride every 24 hours for five (5) consecutive days; a total of 5 doses</description>
    <arm_group_label>Placebo Arm 0.9% sodium chloride</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or Female age 18 or older&#xD;
&#xD;
          2. On high flow oxygen =/&gt; 6 liters nasal cannula (or)&#xD;
&#xD;
          3. On mechanical ventilation&#xD;
&#xD;
          4. Clinical diagnosis of COVID-19 &amp; positive PCR test (or)&#xD;
&#xD;
          5. Clinical diagnosis of COVID-19 &amp; negative PCR test with clinical symptoms of COVID-19&#xD;
             and pathognomonic lesions on a chest CT scan&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known allergy to Pulmozyme&#xD;
&#xD;
          2. Less than 18 years of age&#xD;
&#xD;
          3. Grave condition with anticipated death within 48 hours; at the discretion of treating&#xD;
             physician.&#xD;
&#xD;
          4. Enrollment in another clinical trial receiving investigatory drugs&#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>Jon D Simmons, M.D.</last_name>
    <phone>12514459834</phone>
    <email>jdsimmons@health.southalabama.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Wendy Blount, RN, MSN</last_name>
    <phone>2514554566</phone>
    <email>wlblount@health.southalabama.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of South Alabama</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36617</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jon Simmons, M.D.</last_name>
      <phone>251-471-7971</phone>
      <email>jsimmons@health.southalabama.edu</email>
    </contact>
    <contact_backup>
      <last_name>Wendy Blount, RN, MSN</last_name>
      <phone>251-445-9834</phone>
      <email>wlblount@health.southalabama.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Simmons JD, Lee YL, Mulekar S, Kuck JL, Brevard SB, Gonzalez RP, Gillespie MN, Richards WO. Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome in severely injured human subjects. Ann Surg. 2013 Oct;258(4):591-6; discussion 596-8. doi: 10.1097/SLA.0b013e3182a4ea46.</citation>
    <PMID>23979273</PMID>
  </reference>
  <reference>
    <citation>Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010 Mar 4;464(7285):104-7. doi: 10.1038/nature08780.</citation>
    <PMID>20203610</PMID>
  </reference>
  <reference>
    <citation>Schumacker PT, Gillespie MN, Nakahira K, Choi AM, Crouser ED, Piantadosi CA, Bhattacharya J. Mitochondria in lung biology and pathology: more than just a powerhouse. Am J Physiol Lung Cell Mol Physiol. 2014 Jun 1;306(11):L962-74. doi: 10.1152/ajplung.00073.2014. Epub 2014 Apr 18.</citation>
    <PMID>24748601</PMID>
  </reference>
  <reference>
    <citation>Kuck JL, Obiako BO, Gorodnya OM, Pastukh VM, Kua J, Simmons JD, Gillespie MN. Mitochondrial DNA damage-associated molecular patterns mediate a feed-forward cycle of bacteria-induced vascular injury in perfused rat lungs. Am J Physiol Lung Cell Mol Physiol. 2015 May 15;308(10):L1078-85. doi: 10.1152/ajplung.00015.2015. Epub 2015 Mar 20.</citation>
    <PMID>25795724</PMID>
  </reference>
  <reference>
    <citation>Dobson AW, Grishko V, LeDoux SP, Kelley MR, Wilson GL, Gillespie MN. Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death. Am J Physiol Lung Cell Mol Physiol. 2002 Jul;283(1):L205-10. doi: 10.1152/ajplung.00443.2001.</citation>
    <PMID>12060578</PMID>
  </reference>
  <reference>
    <citation>Ruchko MV, Gorodnya OM, Zuleta A, Pastukh VM, Gillespie MN. The DNA glycosylase Ogg1 defends against oxidant-induced mtDNA damage and apoptosis in pulmonary artery endothelial cells. Free Radic Biol Med. 2011 May 1;50(9):1107-13. doi: 10.1016/j.freeradbiomed.2010.10.692. Epub 2010 Oct 20.</citation>
    <PMID>20969951</PMID>
  </reference>
  <reference>
    <citation>Chouteau JM, Obiako B, Gorodnya OM, Pastukh VM, Ruchko MV, Wright AJ, Wilson GL, Gillespie MN. Mitochondrial DNA integrity may be a determinant of endothelial barrier properties in oxidant-challenged rat lungs. Am J Physiol Lung Cell Mol Physiol. 2011 Dec;301(6):L892-8. doi: 10.1152/ajplung.00210.2011. Epub 2011 Sep 2.</citation>
    <PMID>21890512</PMID>
  </reference>
  <reference>
    <citation>Gebb SA, Decoux A, Waggoner A, Wilson GL, Gillespie MN. Mitochondrial DNA damage mediates hyperoxic dysmorphogenesis in rat fetal lung explants. Neonatology. 2013;103(2):91-7. doi: 10.1159/000342632. Epub 2012 Nov 15.</citation>
    <PMID>23154780</PMID>
  </reference>
  <reference>
    <citation>Hashizume M, Mouner M, Chouteau JM, Gorodnya OM, Ruchko MV, Potter BJ, Wilson GL, Gillespie MN, Parker JC. Mitochondrial-targeted DNA repair enzyme 8-oxoguanine DNA glycosylase 1 protects against ventilator-induced lung injury in intact mice. Am J Physiol Lung Cell Mol Physiol. 2013 Feb 15;304(4):L287-97. doi: 10.1152/ajplung.00071.2012. Epub 2012 Dec 14.</citation>
    <PMID>23241530</PMID>
  </reference>
  <reference>
    <citation>Simmons JD, Freno DR, Muscat CA, Obiako B, Lee YL, Pastukh VM, Brevard SB, Gillespie MN. Mitochondrial DNA damage associated molecular patterns in ventilator-associated pneumonia: Prevention and reversal by intratracheal DNase I. J Trauma Acute Care Surg. 2017 Jan;82(1):120-125. doi: 10.1097/TA.0000000000001269.</citation>
    <PMID>27787436</PMID>
  </reference>
  <reference>
    <citation>Grishko V, Solomon M, Wilson GL, LeDoux SP, Gillespie MN. Oxygen radical-induced mitochondrial DNA damage and repair in pulmonary vascular endothelial cell phenotypes. Am J Physiol Lung Cell Mol Physiol. 2001 Jun;280(6):L1300-8. doi: 10.1152/ajplung.2001.280.6.L1300.</citation>
    <PMID>11350811</PMID>
  </reference>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>May 26, 2021</last_update_submitted>
  <last_update_submitted_qc>May 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of South Alabama</investigator_affiliation>
    <investigator_full_name>Jon Simmons</investigator_full_name>
    <investigator_title>Chief, Division of Trauma &amp; Acute Care Surgery</investigator_title>
  </responsible_party>
  <keyword>Covid-19, Coronavirus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 27, 2023</submitted>
    <returned>July 19, 2023</returned>
  </pending_results>
  <!-- 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/NCT04445285
org study id: USAH 1002 000
nct id: NCT04445285
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This Phase 2 Randomized Placebo Controlled Trial will determine if administering nebulized
      Dornase Alpha (rhDNase) to COVID-19 patients with respiratory failure is safe and will reduce
      28-day mortality.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Mortality at 28 days
time frame: 28 days after enrollment
description: All Cause Mortality at 28 days
measure: Systemic Therapeutic Response
time frame: 5 days after enrollment
description: To assess the effect of Pulmozyme® on the severity of respiratory failure, systemic inflammatory response, and multi-organ failure.
measure: Respiratory Response
time frame: 28 days
description: Proportion of patients alive and free of invasive mechanical ventilation at 28 days invasive mechanical ventilation at 28 days
measure: Legnth of ICU Stay
time frame: 28 days
description: Proportion of patients alive and discharged from the ICU at 28 days discharged from the ICU at 28 days
measure: Legnth of Hospital Stay
time frame: 28 days
description: Proportion of patients alive and discharged from the hospital at 28 days
measure: Respiratory Response
time frame: 28 days
description: Alive, respiratory failure-free days at 28 days
measure: Pulmonary Function
time frame: 5 days
description: Pulmonary Function Ratio at 5 days
arm group label: Treatment Arm
arm group type: Experimental
description: Patient will receive 2.5mg Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase) aerosolized treatment once every 24 hours for five (5) consecutive days; a total of five (5) doses.
arm group label: Placebo Arm 0.9% sodium chloride
arm group type: Placebo Comparator
description: Patient will receive 2.5ml of Sodium Chloride 0.9% aerosolized treatment once every 24 hours for five (5) consecutive days; a total of five (5) doses.
intervention type: Drug
intervention name: Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase)
description: 2.5mg Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase) aerosolized treatment once every 24 hours for five (5) consecutive days; a total of five (5) doses
arm group label: Treatment Arm
intervention type: Drug
intervention name: 0.9%sodium chloride
description: Placebo of 0.9% sodium chloride every 24 hours for five (5) consecutive days; a total of 5 doses
arm group label: Placebo Arm 0.9% sodium chloride
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jon D Simmons, M.D.
phone: 12514459834
email: jdsimmons@health.southalabama.edu
last name: Wendy Blount, RN, MSN
phone: 2514554566
email: wlblount@health.southalabama.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
citation: Simmons JD, Lee YL, Mulekar S, Kuck JL, Brevard SB, Gonzalez RP, Gillespie MN, Richards WO. Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome in severely injured human subjects. Ann Surg. 2013 Oct;258(4):591-6; discussion 596-8. doi: 10.1097/SLA.0b013e3182a4ea46.
PMID: 23979273
citation: Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010 Mar 4;464(7285):104-7. doi: 10.1038/nature08780.
PMID: 20203610
citation: Schumacker PT, Gillespie MN, Nakahira K, Choi AM, Crouser ED, Piantadosi CA, Bhattacharya J. Mitochondria in lung biology and pathology: more than just a powerhouse. Am J Physiol Lung Cell Mol Physiol. 2014 Jun 1;306(11):L962-74. doi: 10.1152/ajplung.00073.2014. Epub 2014 Apr 18.
PMID: 24748601
citation: Kuck JL, Obiako BO, Gorodnya OM, Pastukh VM, Kua J, Simmons JD, Gillespie MN. Mitochondrial DNA damage-associated molecular patterns mediate a feed-forward cycle of bacteria-induced vascular injury in perfused rat lungs. Am J Physiol Lung Cell Mol Physiol. 2015 May 15;308(10):L1078-85. doi: 10.1152/ajplung.00015.2015. Epub 2015 Mar 20.
PMID: 25795724
citation: Dobson AW, Grishko V, LeDoux SP, Kelley MR, Wilson GL, Gillespie MN. Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death. Am J Physiol Lung Cell Mol Physiol. 2002 Jul;283(1):L205-10. doi: 10.1152/ajplung.00443.2001.
PMID: 12060578
citation: Ruchko MV, Gorodnya OM, Zuleta A, Pastukh VM, Gillespie MN. The DNA glycosylase Ogg1 defends against oxidant-induced mtDNA damage and apoptosis in pulmonary artery endothelial cells. Free Radic Biol Med. 2011 May 1;50(9):1107-13. doi: 10.1016/j.freeradbiomed.2010.10.692. Epub 2010 Oct 20.
PMID: 20969951
citation: Chouteau JM, Obiako B, Gorodnya OM, Pastukh VM, Ruchko MV, Wright AJ, Wilson GL, Gillespie MN. Mitochondrial DNA integrity may be a determinant of endothelial barrier properties in oxidant-challenged rat lungs. Am J Physiol Lung Cell Mol Physiol. 2011 Dec;301(6):L892-8. doi: 10.1152/ajplung.00210.2011. Epub 2011 Sep 2.
PMID: 21890512
citation: Gebb SA, Decoux A, Waggoner A, Wilson GL, Gillespie MN. Mitochondrial DNA damage mediates hyperoxic dysmorphogenesis in rat fetal lung explants. Neonatology. 2013;103(2):91-7. doi: 10.1159/000342632. Epub 2012 Nov 15.
PMID: 23154780
citation: Hashizume M, Mouner M, Chouteau JM, Gorodnya OM, Ruchko MV, Potter BJ, Wilson GL, Gillespie MN, Parker JC. Mitochondrial-targeted DNA repair enzyme 8-oxoguanine DNA glycosylase 1 protects against ventilator-induced lung injury in intact mice. Am J Physiol Lung Cell Mol Physiol. 2013 Feb 15;304(4):L287-97. doi: 10.1152/ajplung.00071.2012. Epub 2012 Dec 14.
PMID: 23241530
citation: Simmons JD, Freno DR, Muscat CA, Obiako B, Lee YL, Pastukh VM, Brevard SB, Gillespie MN. Mitochondrial DNA damage associated molecular patterns in ventilator-associated pneumonia: Prevention and reversal by intratracheal DNase I. J Trauma Acute Care Surg. 2017 Jan;82(1):120-125. doi: 10.1097/TA.0000000000001269.
PMID: 27787436
citation: Grishko V, Solomon M, Wilson GL, LeDoux SP, Gillespie MN. Oxygen radical-induced mitochondrial DNA damage and repair in pulmonary vascular endothelial cell phenotypes. Am J Physiol Lung Cell Mol Physiol. 2001 Jun;280(6):L1300-8. doi: 10.1152/ajplung.2001.280.6.L1300.
PMID: 11350811
responsible party type: Sponsor-Investigator
investigator affiliation: University of South Alabama
investigator full name: Jon Simmons
investigator title: Chief, Division of Trauma & Acute Care Surgery
mesh term: COVID-19
mesh term: Respiratory Insufficiency
sharing ipd: Undecided
submitted: June 27, 2023
returned: July 19, 2023