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

NCT04466683 | Active Not Recruiting Phase 2 DMC FDA Device

• 1 other identifier: PREVENT
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 7

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.

Conditions

Covid-19; Sars-CoV2; Pneumonia

Keywords

radiation; radiotherapy; Linac

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

• 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%

  up to 30 days from the last patient enrollment in Step 2 which is estimated to be about 2 years.

Secondary Outcomes (1)

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

  The discharge of the last patient enrolled is estimated to be about 2 years.

Other Outcomes (8)

• Changes in lymphocyte count between control and experimental arms

  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.

• Changes in neutrophil count between control and experimental arms

  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

• Changes in neutrophil to lymphocyte ratio between control and experimental arms

  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

Study Arms (3)

Low radiation arm

EXPERIMENTAL

A single dose of 35 cGY delivered to the whole thorax

Radiation: Low dose radiation 35 cGy

High radiation arm

EXPERIMENTAL

A single dose of 100 cGY delivered to the whole thorax

Radiation: High dose radiation 100 cGy

Control arm

NO INTERVENTION

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

Interventions

Low dose radiation 35 cGy RADIATION

A dose of 35 cGy of whole thorax irradiation will be delivered at a single timepoint

Low radiation arm

High dose radiation 100 cGy RADIATION

A dose of 100 cGy of whole thorax irradiation will be delivered at a single timepoint

High radiation arm

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Varian Medical Systems: collaborator
• Ohio State University: lead

Study Sites (7)

Boca Raton Regional Hospital Lynn Cancer Institute

Boca Raton, Florida, 33486, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Loyola University Chicago

Maywood, Illinois, 60153, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Lowell General Hospital Cancer Center

Lowell, Massachusetts, 01854, United States

Location

Ohio State University James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

Hospital Universitario San Ignacio

Bogotá, Colombia

Location

Related Publications (1)

• 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.

  PMID: 34992881 DERIVED

MeSH Terms

Conditions

COVID-19; Pneumonia

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Arnab Chakravarti, MD

  James Cancer Hospital, Department of Radiation Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: June 20, 2020
• First Posted: July 10, 2020
• Study Start: August 28, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1); US (6)