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Low-Dose Radiotherapy For Patients With SARS-COV-2 (COVID-19) Pneumonia (PREVENT)

Primary Purpose

Covid-19, Sars-CoV2, Pneumonia

Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Low dose radiation 35 cGy
High dose radiation 100 cGy
Sponsored by
Ohio State University Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid-19 focused on measuring radiation, radiotherapy, Linac

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Laboratory-confirmed diagnosis of SARS-CoV-2 pneumonia
  • Currently hospitalized with COVID-19
  • Symptomatic fever, cough and/or dyspnea for < 9 days
  • Patient or legal/authorized representative can understand and sign the study informed consent document
  • Able to be positioned on a linear-accelerator couch for Radiation Therapy delivery

  • And at least one of the following risk factors for significant pulmonary compromise:

    1. Fever > 102 degrees Fahrenheit during index admission
    2. Respiratory rate of ≥ 26 / minute within 24 hours of screening
    3. SpO2 ≤ 95% on room air within 24 hours of screening
    4. Any patient requiring 4 L/min oxygen therapy to maintain SpO2 >93% within 24 hours of screening
    5. Ratio of partial pressure of arterial oxygen to fraction of inspired air < 320.
  • Patients may be enrolled on this trial while concurrently enrolled on other COVID-19 clinical trials.

Exclusion Criteria:

  • Currently requiring mechanical ventilation

  • Prior thoracic radiotherapy, with the exception of the following:

    1. Breast or post-mastectomy chest wall radiation (without regional nodal irradiation) may be included at the discretion of the site primary investigator, and
    2. Thoracic skin radiation therapy (without regional nodal irradiation) is allowed.
  • Known hereditary syndrome with increased sensitivity to radiotherapy, including ataxia-telangiectasia, xeroderma pigmentosum, and Nijmegen Breakage Syndrome
  • Known prior systemic use of the following drugs: Bleomycin, Carmustine, Methotrexate, Busulfan, Cyclophosphamide, or Amiodarone
  • History of or current diagnosis of pulmonary fibrosis, or an alternative pulmonary condition responsible for significant lung compromise at the discretion of the site primary investigator
  • History of lung lobectomy or pneumonectomy
  • Known history of pulmonary sarcoidosis, Wegener's granulomatosis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, polymyositis/dermatomyositis, Sjögren's syndrome, mixed connective tissue disease, Churg-Strauss syndrome, Goodpasture's syndrome, or ankylosing spondylitis.
  • Symptomatic congestive heart failure within the past 6 months including during current hospitalization
  • History of recent or current malignancy receiving any cytotoxic chemotherapy or immunotherapy within the past 6 months.
  • History of bone marrow transplantation.
  • History of any solid organ transplant (renal, cardiac, liver, lung) requiring immunosuppressive therapy.
  • Females who are pregnant or breast feeding.
  • Inability to undergo radiotherapy for any other medical or cognitive issues.

Sites / Locations

  • Boca Raton Regional Hospital Lynn Cancer InstituteRecruiting
  • Miami Cancer InstituteRecruiting
  • Loyola University ChicagoRecruiting
  • Indiana University School of MedicineRecruiting
  • Lowell General Hospital Cancer CenterRecruiting
  • Beaumont HospitalRecruiting
  • Ohio State University James Cancer HospitalRecruiting
  • Hospital Universitario San IgnacioRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

No Intervention

Arm Label

Low radiation arm

High radiation arm

Control arm

Arm Description

A single dose of 35 cGY delivered to the whole thorax

A single dose of 100 cGY delivered to the whole thorax

Patients will receive no radiation therapy but will have research samples collected and best supportive care

Outcomes

Primary Outcome Measures

Step 1 Dose selection
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.
Clinical benefit of Step 2 Radiation dose
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%

Secondary Outcome Measures

Changes of the cost of care for the control arm versus the radiation arms
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.

Full Information

First Posted
June 20, 2020
Last Updated
March 11, 2021
Sponsor
Ohio State University Comprehensive Cancer Center
Collaborators
Varian Medical Systems
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1. Study Identification

Unique Protocol Identification Number
NCT04466683
Brief Title
Low-Dose Radiotherapy For Patients With SARS-COV-2 (COVID-19) Pneumonia
Acronym
PREVENT
Official Title
Phase II Protocol of Low-Dose Whole Thorax Megavoltage Radiotherapy for Patients With SARS-COV-2 Pneumonia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
August 28, 2020 (Actual)
Primary Completion Date
December 31, 2021 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University Comprehensive Cancer Center
Collaborators
Varian Medical Systems

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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 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. 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 : Rate of mechanical ventilation (MV) Rate of prolonged hospital stay >10 days (PHS) Crude all-cause mortality rate at the time of analysis 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: Days of mechanical ventilation Days of hospitalization. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid-19, Sars-CoV2, Pneumonia
Keywords
radiation, radiotherapy, Linac

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low radiation arm
Arm Type
Experimental
Arm Description
A single dose of 35 cGY delivered to the whole thorax
Arm Title
High radiation arm
Arm Type
Experimental
Arm Description
A single dose of 100 cGY delivered to the whole thorax
Arm Title
Control arm
Arm Type
No Intervention
Arm Description
Patients will receive no radiation therapy but will have research samples collected and best supportive care
Intervention Type
Radiation
Intervention Name(s)
Low dose radiation 35 cGy
Intervention Description
A dose of 35 cGy of whole thorax irradiation will be delivered at a single timepoint
Intervention Type
Radiation
Intervention Name(s)
High dose radiation 100 cGy
Intervention Description
A dose of 100 cGy of whole thorax irradiation will be delivered at a single timepoint
Primary Outcome Measure Information:
Title
Step 1 Dose selection
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.
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.
Title
Clinical benefit of Step 2 Radiation dose
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%
Time Frame
up to 30 days from the last patient enrollment in Step 2 which is estimated to be about 2 years.
Secondary Outcome Measure Information:
Title
Changes of the cost of care for the control arm versus the radiation arms
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.
Time Frame
The discharge of the last patient enrolled is estimated to be about 2 years.
Other Pre-specified Outcome Measures:
Title
Changes in lymphocyte count between control and experimental arms
Description
Compare differences within and between arms lymphocyte count in K/ul.
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.
Title
Changes in neutrophil count between control and experimental arms
Description
Compare differences within and between arms neutrophil count in K/ul .
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
Title
Changes in neutrophil to lymphocyte ratio between control and experimental arms
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.
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
Title
Changes in blood C-reactive protein between control and experimental arms
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.
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
Title
Changes in blood IL-6 levels between control and experimental arms
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.
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
Title
Changes in blood D-Dimer levels between control and experimental arms
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.
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
Title
Changes in blood Lactate dehydrogenase (LDH) levels between control and experimental arms
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.
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
Title
Changes in blood ferritin levels between control and experimental arms
Description
Compare differences within and between arms for ferritin in ng/ml. A decrease in Ferritin value would indicate a more favorable treatment outcome.
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Laboratory-confirmed diagnosis of SARS-CoV-2 pneumonia Currently hospitalized with COVID-19 Symptomatic fever, cough and/or dyspnea for < 9 days Patient or legal/authorized representative can understand and sign the study informed consent document Able to be positioned on a linear-accelerator couch for Radiation Therapy delivery And at least one of the following risk factors for significant pulmonary compromise: Fever > 102 degrees Fahrenheit during index admission Respiratory rate of ≥ 26 / minute within 24 hours of screening SpO2 ≤ 95% on room air within 24 hours of screening Any patient requiring 4 L/min oxygen therapy to maintain SpO2 >93% within 24 hours of screening Ratio of partial pressure of arterial oxygen to fraction of inspired air < 320. Patients may be enrolled on this trial while concurrently enrolled on other COVID-19 clinical trials. Exclusion Criteria: Currently requiring mechanical ventilation Prior thoracic radiotherapy, with the exception of the following: Breast or post-mastectomy chest wall radiation (without regional nodal irradiation) may be included at the discretion of the site primary investigator, and Thoracic skin radiation therapy (without regional nodal irradiation) is allowed. Known hereditary syndrome with increased sensitivity to radiotherapy, including ataxia-telangiectasia, xeroderma pigmentosum, and Nijmegen Breakage Syndrome Known prior systemic use of the following drugs: Bleomycin, Carmustine, Methotrexate, Busulfan, Cyclophosphamide, or Amiodarone History of or current diagnosis of pulmonary fibrosis, or an alternative pulmonary condition responsible for significant lung compromise at the discretion of the site primary investigator History of lung lobectomy or pneumonectomy Known history of pulmonary sarcoidosis, Wegener's granulomatosis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, polymyositis/dermatomyositis, Sjögren's syndrome, mixed connective tissue disease, Churg-Strauss syndrome, Goodpasture's syndrome, or ankylosing spondylitis. Symptomatic congestive heart failure within the past 6 months including during current hospitalization History of recent or current malignancy receiving any cytotoxic chemotherapy or immunotherapy within the past 6 months. History of bone marrow transplantation. History of any solid organ transplant (renal, cardiac, liver, lung) requiring immunosuppressive therapy. Females who are pregnant or breast feeding. Inability to undergo radiotherapy for any other medical or cognitive issues.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Arnab Chakravarti, MD
Phone
614-293-0672
Email
Arnab.Chakravarti@osumc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kimberly Mahler
Phone
614-685-4247
Email
kimberly.mahler@osumc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arnab Chakravarti, MD
Organizational Affiliation
James Cancer Hospital, Department of Radiation Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Boca Raton Regional Hospital Lynn Cancer Institute
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Viviana Boronat
Phone
561-955-4145
Email
Vbornat@baptisthealth.net
Facility Name
Miami Cancer Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alex Kudryashev
Email
AlexKu@baptisthealth.net
First Name & Middle Initial & Last Name & Degree
Minesh Mehta, MD
Facility Name
Loyola University Chicago
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Fargo
Phone
708-216-8046
Email
sfargo@luc.edu
First Name & Middle Initial & Last Name & Degree
William Small, MD
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amy Miller
Phone
317-944-1242
Email
amym@iu.edu
First Name & Middle Initial & Last Name & Degree
Paul Anthony, MD
Facility Name
Lowell General Hospital Cancer Center
City
Lowell
State/Province
Massachusetts
ZIP/Postal Code
01854
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gayle Hincks
Phone
978-788-7084
Email
gayle.hincks@lowellgeneral.org
First Name & Middle Initial & Last Name & Degree
Matthew Katz, MD
Facility Name
Beaumont Hospital
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Grace San Agustin
Phone
248-551-7835
Email
grace.sanagustin@beaumont.org
First Name & Middle Initial & Last Name & Degree
James Fontanesi, MD
Facility Name
Ohio State University James Cancer Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kimberly Mahler
Phone
614-685-4247
Email
kimberly.mahler@osumc.edu
First Name & Middle Initial & Last Name & Degree
Isabel Manring
Phone
6143663760
Email
isabel.manring@osumc.edu
First Name & Middle Initial & Last Name & Degree
Arnab Chakravarti, MD
Facility Name
Hospital Universitario San Ignacio
City
Bogotá
Country
Colombia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angelica Maria Arango Gutierrez
Email
amarangog@husi.org.co
First Name & Middle Initial & Last Name & Degree
Juan Carlos Galvis Serrano, MD
Email
jcgalvis@husi.org.co
First Name & Middle Initial & Last Name & Degree
Juan Carlos Galvis Serrano

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34992881
Citation
McClelland S 3rd, Miller AC, Williams MD, Anthony BP, Chakravarti A, Anthony PA. Low-dose whole thorax radiation therapy for COVID-19 pneumonia: inpatient onboarding process for a randomized controlled trial. Rep Pract Oncol Radiother. 2021 Dec 30;26(6):1057-1059. doi: 10.5603/RPOR.a2021.0112. eCollection 2021.
Results Reference
derived

Learn more about this trial

Low-Dose Radiotherapy For Patients With SARS-COV-2 (COVID-19) Pneumonia

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