<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/NCT04466683</url>
  </required_header>
  <id_info>
    <org_study_id>PREVENT</org_study_id>
    <nct_id>NCT04466683</nct_id>
  </id_info>
  <brief_title>Low-Dose Radiotherapy For Patients With SARS-COV-2 (COVID-19) Pneumonia</brief_title>
  <acronym>PREVENT</acronym>
  <official_title>Phase II Protocol of Low-Dose Whole Thorax Megavoltage Radiotherapy for Patients With SARS-COV-2 Pneumonia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ohio State University Comprehensive Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Varian Medical Systems</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Ohio State University Comprehensive Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Low doses of radiation in the form of chest x-rays has been in the past to treat people with&#xD;
      pneumonia. This treatment was thought to reduce inflammation and was found to be effective&#xD;
      without side effects. However, it was an expensive treatment and was eventually replaced with&#xD;
      less expensive treatment options like penicillin.&#xD;
&#xD;
      The COVID-19 virus has emerged recently, causing high rates of pneumonia in people. The&#xD;
      authors believe that giving a small dose of radiation to the lungs may reduce inflammation&#xD;
      and neutralize the pneumonia caused by COVID-19. For this study, the x-ray given is called&#xD;
      radiation therapy. Radiation therapy uses high-energy X-ray beams from a large machine to&#xD;
      target the lungs and reduce inflammation. Usually, it is given at much higher doses to treat&#xD;
      cancers.&#xD;
&#xD;
      The purpose of this study is to find out if adding a single treatment of low-dose x-rays to&#xD;
      the lungs might reduce the amount of inflammation in the lungs from COVID-19 infection, which&#xD;
      could reduce the need for a ventilator or breathing tube.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The authors propose a two-step randomized Phase II study to determine if single fraction low&#xD;
      dose whole thorax megavoltage radiotherapy (LD-WTRT) can produce meaningful clinical benefit&#xD;
      in COVID-19 patients. In Step 1, patients would be randomized 1:2 to standard of care without&#xD;
      or with LD-WTRT. Patients randomized to LD-WTRT would be further randomized to either 35 cGy&#xD;
      or 100 cGy. After 20 patients have been enrolled on each low-dose radiotherapy arm, they will&#xD;
      be evaluated to determine the selection of the &quot;best radiotherapy dose-arm&quot; for the remainder&#xD;
      of the patients. This will be done by analyzing clinical benefit, risk profile, and the&#xD;
      dynamics of biomarker change, specifically focusing on IL-6&#xD;
&#xD;
        1. If the rate of Grade 4 toxicity is lower by an absolute rate of 15% when comparing the&#xD;
           35 cGy and 100 cGy arms, the arm with the lower toxicity rate will be used for Step 2 of&#xD;
           the trial.&#xD;
&#xD;
        2. If the crude clinically meaningful event rate (CMER) which is a composite endpoint, is&#xD;
           lower by an absolute rate of 20% when comparing the 35 cGy and 100 cGy arms, the lower&#xD;
           CMER rate arm will be used for Step 2. CMER is defined as a composite of :&#xD;
&#xD;
             1. Rate of mechanical ventilation (MV)&#xD;
&#xD;
             2. Rate of prolonged hospital stay &gt;10 days (PHS)&#xD;
&#xD;
             3. Crude all-cause mortality rate at the time of analysis&#xD;
&#xD;
        3. If the crude CMER is &lt; 20% difference between the 35 cGy and 100 cGy arms, the&#xD;
           investigators will determine whether there is a trend suggesting less Facility Resource&#xD;
           Utilization Rate (FRUR). If the FRUR is 20% lower in either the 35 cGy or 100 cGy arms,&#xD;
           that dose will be used for Step 2. The FRUR is based upon:&#xD;
&#xD;
             1. Days of mechanical ventilation&#xD;
&#xD;
             2. Days of hospitalization.&#xD;
&#xD;
        4. If both crude CMER and FRU rates do not differ by at least 20%, the investigators will&#xD;
           evaluate the area under the curve (AUC) for IL-6 levels drawn within 24 hours before&#xD;
           LD-WTRT and at 48 hours (2d) and 168 hours (7d) after radiation. If one of the two arms&#xD;
           has a 20% lower serum IL-6 AUC one week after radiotherapy, the investigators will&#xD;
           select that arm for Step 2.&#xD;
&#xD;
        5. If none of the parameters in numbers 1-4 above differ in the criteria listed, the&#xD;
           investigators will use the lower dose of 35 cGy for Step 2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 28, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 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>
    <intervention_model_description>Subjects will be randomized 2:1 to receive radiation therapy (2 different doses) or control (no radiation). Sixty subjects will be enrolled to 3 arms and the best dose chosen after enrolling 60 subjects. Randomization of an additional 40 subjects will be randomized 2:1 to receive radiation therapy (best dose) versus control with no radiation.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Step 1 Dose selection</measure>
    <time_frame>At least 2 weeks after the 60th patient enrolled has been evaluated for adverse events. It is estimated that the time frame will be about 1 year to complete enrollment.</time_frame>
    <description>The rate of grade 4 toxicity, the rate of mechanical ventilation, the rate of hospital stay greater than 10 days, and the crude all-cause mortality rate will be used to calculate the clinically meaningful event rate (CMER). The rates range would be from 0 to 100% with a lower rate indicating a more favorable dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical benefit of Step 2 Radiation dose</measure>
    <time_frame>up to 30 days from the last patient enrollment in Step 2 which is estimated to be about 2 years.</time_frame>
    <description>Clinical benefit will have the composite endpoint with the following 3 elements: the rate of mechanical ventilation, the rate of hospital stays of greater than 10 days and the rate of all-cause mortality at 30 from enrollment. A lower rate would indicate a positive clinical benefit and would range from 0 to 100%</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes of the cost of care for the control arm versus the radiation arms</measure>
    <time_frame>The discharge of the last patient enrolled is estimated to be about 2 years.</time_frame>
    <description>Billing codes will be collected to determine the total cost of hospitalization for each patient at discharge. The cost of hospitalization for the control arm versus experimental radiation arms will be compared.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in lymphocyte count between control and experimental arms</measure>
    <time_frame>Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization.</time_frame>
    <description>Compare differences within and between arms lymphocyte count in K/ul.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in neutrophil count between control and experimental arms</measure>
    <time_frame>Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization</time_frame>
    <description>Compare differences within and between arms neutrophil count in K/ul .</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in neutrophil to lymphocyte ratio between control and experimental arms</measure>
    <time_frame>Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization</time_frame>
    <description>Compare differences within and between arms for the neutrophil to lymphocyte ratio. A decrease in the ratio of neutrophil to lymphocyte count would indicate a more favorable treatment outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in blood C-reactive protein between control and experimental arms</measure>
    <time_frame>Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization</time_frame>
    <description>Compare differences within and between arms for the C-reactive protein in mg/L. A decrease in C-reactive protein value would indicate a more favorable treatment outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in blood IL-6 levels between control and experimental arms</measure>
    <time_frame>Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization</time_frame>
    <description>Compare differences within and between arms for the IL-6 in pg/ml. A decrease in IL-6 value would indicate a more favorable treatment outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in blood D-Dimer levels between control and experimental arms</measure>
    <time_frame>Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization</time_frame>
    <description>Compare differences within and between arms for the D-Dimer in mcg/ml. A decrease in D-Dimer value would indicate a more favorable treatment outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in blood Lactate dehydrogenase (LDH) levels between control and experimental arms</measure>
    <time_frame>Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization</time_frame>
    <description>Compare differences within and between arms for the LDH in U/L. A decrease in LDH value would indicate a more favorable treatment outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in blood ferritin levels between control and experimental arms</measure>
    <time_frame>Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization</time_frame>
    <description>Compare differences within and between arms for ferritin in ng/ml. A decrease in Ferritin value would indicate a more favorable treatment outcome.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Covid-19</condition>
  <condition>Sars-CoV2</condition>
  <condition>Pneumonia</condition>
  <arm_group>
    <arm_group_label>Low radiation arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single dose of 35 cGY delivered to the whole thorax</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High radiation arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single dose of 100 cGY delivered to the whole thorax</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients will receive no radiation therapy but will have research samples collected and best supportive care</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Low dose radiation 35 cGy</intervention_name>
    <description>A dose of 35 cGy of whole thorax irradiation will be delivered at a single timepoint</description>
    <arm_group_label>Low radiation arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>High dose radiation 100 cGy</intervention_name>
    <description>A dose of 100 cGy of whole thorax irradiation will be delivered at a single timepoint</description>
    <arm_group_label>High radiation arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Laboratory-confirmed diagnosis of SARS-CoV-2 pneumonia&#xD;
&#xD;
          -  Currently hospitalized with COVID-19&#xD;
&#xD;
          -  Symptomatic fever, cough and/or dyspnea for &lt; 9 days&#xD;
&#xD;
          -  Patient or legal/authorized representative can understand and sign the study informed&#xD;
             consent document&#xD;
&#xD;
          -  Able to be positioned on a linear-accelerator couch for Radiation Therapy delivery&#xD;
&#xD;
          -  And at least one of the following risk factors for significant pulmonary compromise:&#xD;
&#xD;
               1. Fever &gt; 102 degrees Fahrenheit during index admission&#xD;
&#xD;
               2. Respiratory rate of ≥ 26 / minute within 24 hours of screening&#xD;
&#xD;
               3. SpO2 ≤ 95% on room air within 24 hours of screening&#xD;
&#xD;
               4. Any patient requiring 4 L/min oxygen therapy to maintain SpO2 &gt;93% within 24&#xD;
                  hours of screening&#xD;
&#xD;
               5. Ratio of partial pressure of arterial oxygen to fraction of inspired air &lt; 320.&#xD;
&#xD;
          -  Patients may be enrolled on this trial while concurrently enrolled on other COVID-19&#xD;
             clinical trials.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently requiring mechanical ventilation&#xD;
&#xD;
          -  Prior thoracic radiotherapy, with the exception of the following:&#xD;
&#xD;
               1. Breast or post-mastectomy chest wall radiation (without regional nodal&#xD;
                  irradiation) may be included at the discretion of the site primary investigator,&#xD;
                  and&#xD;
&#xD;
               2. Thoracic skin radiation therapy (without regional nodal irradiation) is allowed.&#xD;
&#xD;
          -  Known hereditary syndrome with increased sensitivity to radiotherapy, including&#xD;
             ataxia-telangiectasia, xeroderma pigmentosum, and Nijmegen Breakage Syndrome&#xD;
&#xD;
          -  Known prior systemic use of the following drugs: Bleomycin, Carmustine, Methotrexate,&#xD;
             Busulfan, Cyclophosphamide, or Amiodarone&#xD;
&#xD;
          -  History of or current diagnosis of pulmonary fibrosis, or an alternative pulmonary&#xD;
             condition responsible for significant lung compromise at the discretion of the site&#xD;
             primary investigator&#xD;
&#xD;
          -  History of lung lobectomy or pneumonectomy&#xD;
&#xD;
          -  Known history of pulmonary sarcoidosis, Wegener's granulomatosis, systemic lupus&#xD;
             erythematosus, rheumatoid arthritis, systemic sclerosis, polymyositis/dermatomyositis,&#xD;
             Sjögren's syndrome, mixed connective tissue disease, Churg-Strauss syndrome,&#xD;
             Goodpasture's syndrome, or ankylosing spondylitis.&#xD;
&#xD;
          -  Symptomatic congestive heart failure within the past 6 months including during current&#xD;
             hospitalization&#xD;
&#xD;
          -  History of recent or current malignancy receiving any cytotoxic chemotherapy or&#xD;
             immunotherapy within the past 6 months.&#xD;
&#xD;
          -  History of bone marrow transplantation.&#xD;
&#xD;
          -  History of any solid organ transplant (renal, cardiac, liver, lung) requiring&#xD;
             immunosuppressive therapy.&#xD;
&#xD;
          -  Females who are pregnant or breast feeding.&#xD;
&#xD;
          -  Inability to undergo radiotherapy for any other medical or cognitive issues.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Arnab Chakravarti, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>James Cancer Hospital, Department of Radiation Oncology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Arnab Chakravarti, MD</last_name>
    <phone>614-293-0672</phone>
    <email>Arnab.Chakravarti@osumc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kimberly Mahler</last_name>
    <phone>614-685-4247</phone>
    <email>kimberly.mahler@osumc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Boca Raton Regional Hospital Lynn Cancer Institute</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Viviana Boronat</last_name>
      <phone>561-955-4145</phone>
      <email>Vbornat@baptisthealth.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Miami Cancer Institute</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alex Kudryashev</last_name>
      <email>AlexKu@baptisthealth.net</email>
    </contact>
    <investigator>
      <last_name>Minesh Mehta, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Loyola University Chicago</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susan Fargo</last_name>
      <phone>708-216-8046</phone>
      <email>sfargo@luc.edu</email>
    </contact>
    <investigator>
      <last_name>William Small, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Indiana University School of Medicine</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amy Miller</last_name>
      <phone>317-944-1242</phone>
      <email>amym@iu.edu</email>
    </contact>
    <investigator>
      <last_name>Paul Anthony, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Lowell General Hospital Cancer Center</name>
      <address>
        <city>Lowell</city>
        <state>Massachusetts</state>
        <zip>01854</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gayle Hincks</last_name>
      <phone>978-788-7084</phone>
      <email>gayle.hincks@lowellgeneral.org</email>
    </contact>
    <investigator>
      <last_name>Matthew Katz, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Beaumont Hospital</name>
      <address>
        <city>Royal Oak</city>
        <state>Michigan</state>
        <zip>48073</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Grace San Agustin</last_name>
      <phone>248-551-7835</phone>
      <email>grace.sanagustin@beaumont.org</email>
    </contact>
    <investigator>
      <last_name>James Fontanesi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ohio State University James Cancer Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kimberly Mahler</last_name>
      <phone>614-685-4247</phone>
      <email>kimberly.mahler@osumc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Isabel Manring</last_name>
      <phone>6143663760</phone>
      <email>isabel.manring@osumc.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Arnab Chakravarti, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario San Ignacio</name>
      <address>
        <city>Bogotá</city>
        <country>Colombia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Angelica Maria Arango Gutierrez</last_name>
      <email>amarangog@husi.org.co</email>
    </contact>
    <contact_backup>
      <last_name>Juan Carlos Galvis Serrano, MD</last_name>
      <email>jcgalvis@husi.org.co</email>
    </contact_backup>
    <investigator>
      <last_name>Juan Carlos Galvis Serrano</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Colombia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>June 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>March 11, 2021</last_update_submitted>
  <last_update_submitted_qc>March 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ohio State University Comprehensive Cancer Center</investigator_affiliation>
    <investigator_full_name>Arnab Chakravarti</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>radiation</keyword>
  <keyword>radiotherapy</keyword>
  <keyword>Linac</keyword>
  <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>
  <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/NCT04466683
org study id: PREVENT
nct id: NCT04466683
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
Low doses of radiation in the form of chest x-rays has been in the past to treat people with
      pneumonia. This treatment was thought to reduce inflammation and was found to be effective
      without side effects. However, it was an expensive treatment and was eventually replaced with
      less expensive treatment options like penicillin.

      The COVID-19 virus has emerged recently, causing high rates of pneumonia in people. The
      authors believe that giving a small dose of radiation to the lungs may reduce inflammation
      and neutralize the pneumonia caused by COVID-19. For this study, the x-ray given is called
      radiation therapy. Radiation therapy uses high-energy X-ray beams from a large machine to
      target the lungs and reduce inflammation. Usually, it is given at much higher doses to treat
      cancers.

      The purpose of this study is to find out if adding a single treatment of low-dose x-rays to
      the lungs might reduce the amount of inflammation in the lungs from COVID-19 infection, which
      could reduce the need for a ventilator or breathing tube.
The authors propose a two-step randomized Phase II study to determine if single fraction low
      dose whole thorax megavoltage radiotherapy (LD-WTRT) can produce meaningful clinical benefit
      in COVID-19 patients. In Step 1, patients would be randomized 1:2 to standard of care without
      or with LD-WTRT. Patients randomized to LD-WTRT would be further randomized to either 35 cGy
      or 100 cGy. After 20 patients have been enrolled on each low-dose radiotherapy arm, they will
      be evaluated to determine the selection of the "best radiotherapy dose-arm" for the remainder
      of the patients. This will be done by analyzing clinical benefit, risk profile, and the
      dynamics of biomarker change, specifically focusing on IL-6

        1. If the rate of Grade 4 toxicity is lower by an absolute rate of 15% when comparing the
           35 cGy and 100 cGy arms, the arm with the lower toxicity rate will be used for Step 2 of
           the trial.

        2. If the crude clinically meaningful event rate (CMER) which is a composite endpoint, is
           lower by an absolute rate of 20% when comparing the 35 cGy and 100 cGy arms, the lower
           CMER rate arm will be used for Step 2. CMER is defined as a composite of :

             1. Rate of mechanical ventilation (MV)

             2. Rate of prolonged hospital stay >10 days (PHS)

             3. Crude all-cause mortality rate at the time of analysis

        3. If the crude CMER is < 20% difference between the 35 cGy and 100 cGy arms, the
           investigators will determine whether there is a trend suggesting less Facility Resource
           Utilization Rate (FRUR). If the FRUR is 20% lower in either the 35 cGy or 100 cGy arms,
           that dose will be used for Step 2. The FRUR is based upon:

             1. Days of mechanical ventilation

             2. Days of hospitalization.

        4. If both crude CMER and FRU rates do not differ by at least 20%, the investigators will
           evaluate the area under the curve (AUC) for IL-6 levels drawn within 24 hours before
           LD-WTRT and at 48 hours (2d) and 168 hours (7d) after radiation. If one of the two arms
           has a 20% lower serum IL-6 AUC one week after radiotherapy, the investigators will
           select that arm for Step 2.

        5. If none of the parameters in numbers 1-4 above differ in the criteria listed, the
           investigators will use the lower dose of 35 cGy for Step 2.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Subjects will be randomized 2:1 to receive radiation therapy (2 different doses) or control (no radiation). Sixty subjects will be enrolled to 3 arms and the best dose chosen after enrolling 60 subjects. Randomization of an additional 40 subjects will be randomized 2:1 to receive radiation therapy (best dose) versus control with no radiation.
primary purpose: Treatment
masking: None (Open Label)
measure: Step 1 Dose selection
time frame: At least 2 weeks after the 60th patient enrolled has been evaluated for adverse events. It is estimated that the time frame will be about 1 year to complete enrollment.
description: The rate of grade 4 toxicity, the rate of mechanical ventilation, the rate of hospital stay greater than 10 days, and the crude all-cause mortality rate will be used to calculate the clinically meaningful event rate (CMER). The rates range would be from 0 to 100% with a lower rate indicating a more favorable dose.
measure: Clinical benefit of Step 2 Radiation dose
time frame: up to 30 days from the last patient enrollment in Step 2 which is estimated to be about 2 years.
description: Clinical benefit will have the composite endpoint with the following 3 elements: the rate of mechanical ventilation, the rate of hospital stays of greater than 10 days and the rate of all-cause mortality at 30 from enrollment. A lower rate would indicate a positive clinical benefit and would range from 0 to 100%
measure: Changes of the cost of care for the control arm versus the radiation arms
time frame: The discharge of the last patient enrolled is estimated to be about 2 years.
description: Billing codes will be collected to determine the total cost of hospitalization for each patient at discharge. The cost of hospitalization for the control arm versus experimental radiation arms will be compared.
measure: Changes in lymphocyte count between control and experimental arms
time frame: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization.
description: Compare differences within and between arms lymphocyte count in K/ul.
measure: Changes in neutrophil count between control and experimental arms
time frame: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization
description: Compare differences within and between arms neutrophil count in K/ul .
measure: Changes in neutrophil to lymphocyte ratio between control and experimental arms
time frame: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization
description: Compare differences within and between arms for the neutrophil to lymphocyte ratio. A decrease in the ratio of neutrophil to lymphocyte count would indicate a more favorable treatment outcome.
measure: Changes in blood C-reactive protein between control and experimental arms
time frame: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization
description: Compare differences within and between arms for the C-reactive protein in mg/L. A decrease in C-reactive protein value would indicate a more favorable treatment outcome.
measure: Changes in blood IL-6 levels between control and experimental arms
time frame: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization
description: Compare differences within and between arms for the IL-6 in pg/ml. A decrease in IL-6 value would indicate a more favorable treatment outcome.
measure: Changes in blood D-Dimer levels between control and experimental arms
time frame: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization
description: Compare differences within and between arms for the D-Dimer in mcg/ml. A decrease in D-Dimer value would indicate a more favorable treatment outcome.
measure: Changes in blood Lactate dehydrogenase (LDH) levels between control and experimental arms
time frame: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization
description: Compare differences within and between arms for the LDH in U/L. A decrease in LDH value would indicate a more favorable treatment outcome.
measure: Changes in blood ferritin levels between control and experimental arms
time frame: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization
description: Compare differences within and between arms for ferritin in ng/ml. A decrease in Ferritin value would indicate a more favorable treatment outcome.
arm group label: Low radiation arm
arm group type: Experimental
description: A single dose of 35 cGY delivered to the whole thorax
arm group label: High radiation arm
arm group type: Experimental
description: A single dose of 100 cGY delivered to the whole thorax
arm group label: Control arm
arm group type: No Intervention
description: Patients will receive no radiation therapy but will have research samples collected and best supportive care
intervention type: Radiation
intervention name: Low dose radiation 35 cGy
description: A dose of 35 cGy of whole thorax irradiation will be delivered at a single timepoint
arm group label: Low radiation arm
intervention type: Radiation
intervention name: High dose radiation 100 cGy
description: A dose of 100 cGy of whole thorax irradiation will be delivered at a single timepoint
arm group label: High radiation arm
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Arnab Chakravarti, MD
role: Principal Investigator
affiliation: James Cancer Hospital, Department of Radiation Oncology
last name: Arnab Chakravarti, MD
phone: 614-293-0672
email: Arnab.Chakravarti@osumc.edu
last name: Kimberly Mahler
phone: 614-685-4247
email: kimberly.mahler@osumc.edu
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
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facility: 
status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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investigator: 
facility: 
status: Recruiting
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investigator: 
country: Colombia
country: United States
responsible party type: Principal Investigator
investigator affiliation: Ohio State University Comprehensive Cancer Center
investigator full name: Arnab Chakravarti
investigator title: Principal Investigator
mesh term: COVID-19
mesh term: Pneumonia
sharing ipd: No