Low Dose Whole Lung Radiation Therapy for Patients With COVID-19 and Respiratory Compromise (VENTED)

July 28, 2026 updated by: Arnab Chakravarti, Ohio State University

Vented COVID: A Phase II Study Of The Use Of Ultra Low-Dose Bilateral Whole Lung Radiation Therapy in the Treatment Of Critically Ill Patients With COVID-19 Respiratory Compromise

Low doses of radiation in the form of chest X-rays have been used to treat people with pneumonia. This treatment was found to be effective by reducing inflammation and with minimal side effects. However, it was an expensive treatment and was eventually replaced with less costly treatments such as antibiotics. Radiation has also been shown in some animal experiments to reduce some types of inflammation.

Some patients diagnosed with COVID-19 pneumonia will experience worsening disease, which can become very serious, requiring the use of a ventilator. This is caused by inflammation in the lung from the virus and the immune system. 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 a COVID-19 infection, which could help a patient to breathe without use of a ventilator.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The primary outcome is the mortality rate 30 days after the ICU-based mechanical ventilation initiation.Based on current data available, the mortality rate for ventilated patients is assumed to be 80% in the current design. An interim futility analysis will be conducted after 16 evaluable patients have received the ultralow dose-whole lung radiation therapy (ULD-WLRT). If at least 3 patients survive for at least 30 days, we will enroll additional 8 patients (total of 24 patients). Otherwise, the trial will stop for further evaluation. Due to the limited data currently available in local institutions about a 30 day mortality rate , we will retrospectively evaluate the mortality rate of the ventilated patients without the ULD-WLRT in our institution when data is available.

Time to event secondary objectives (e.g. overall survival, time to discharge) analyses will be performed using Kaplan-Meier survival analysis, with a competing risk model (leaving the study because of death), including effects for demographic/clinical characteristics in the model. Proportional endpoints (such as % patients off ventilator) will be calculated along with the 95% Clopper-Pearson exact confidence interval. Pre/post measurements will be evaluated using linear mixed models for repeated measures (with proper data transformation as needed). Association between demographic/clinical characteristics and other secondary objectives (size of ground glass opacities (GGO)/opacification, for example) will be accomplished with generalized linear models.

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Laboratory Diagnosis of COVID-19 based within 14 days of enrollment.
  • CT or radiographic findings typical of COVID-19 pneumonia within 5 days of enrollment
  • Receiving ICU-based mechanical ventilation
  • Life expectancy ≥ 24 hours, as judged by investigator
  • Hypoxemia defined as a Pa/FIO2 ratio < 300 or SpO2/FiO2 < 315
  • Signed informed consent by patient or his or her legal/authorized representative

Exclusion Criteria:

  • Moribund with survival expected < 24 hours, as judged by investigator and treating team
  • Expected survival < 30 days, as judged by investigator and treating team, due to chronic illness present prior to COVID infection
  • Patient or legal representative not committed to full disease specific therapy, i.e. comfort care (DNRCCA is allowed)
  • Treatment with immune suppressing medications in the last 30 days (steroids for acute respiratory distress syndrome or septic shock allowed)
  • Presumed COVID-associated illness greater than 14-days
  • Inpatient admission greater than 14-days
  • Patient deemed unsafe for travel for radiation therapy
  • Chronic hypoxemia requiring supplemental oxygen at baseline
  • Documented active connective tissue disease (scleroderma) or idiopathic pulmonary fibrosis
  • History of prior radiation therapy resulting in ≥grade 2 radiation pneumonitis within 365 days of enrollment
  • Active or history of prior radiation to the thorax completed within 180 days of enrollment (skin or surface only skin treatments are acceptable)
  • Known active uncontrolled bacterial or fungal infections of the lung.
  • Active cytotoxic chemotherapy
  • Females who are pregnant or have a positive pregnancy test
  • Breast feeding
  • Note: concurrent administration of convalescent immune plasma therapy either on clinical trial or as a standard therapy not an exclusion criterion, but will be noted

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Radiation Arm
Each subject will receive a dose of whole lung radiation. A second optional dose of 80 cGy may be delivered if no improvement after 3-10 days.
Radiation: Radiation therapy
Patients will be treated with a single dose of 80 cGy to the bilateral lungs in a manner that is simplified such that it can be designed and delivered quickly in one session. No specific normal tissue constraints are employed in this protocol.
Other Names:
  • Linear accelerator
  • x-rays
  • LINAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality Rate of Subjects Treated With Whole Lung Low-dose Radiation.
Time Frame: up to 1 month post radiation dose
Number of subjects who expire from the date of radiation up to 1 month post radiation dose. The date will be collected if subject expires
up to 1 month post radiation dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To Compare Total Hospital Stay and Length of Hospital Stay After Post Radiation Dose
Time Frame: Until subject discharged for any reason, up to day 47
number of days hospitalized before and after radiation
Until subject discharged for any reason, up to day 47
Evaluate Total and Post-ULD-WLRT ICU Length of Stay
Time Frame: Until subject discharged for any reason, up to day 47
Number of days in ICU after receiving radiation therapy
Until subject discharged for any reason, up to day 47
Number of Days Alive After RT in Days
Time Frame: long term follow, up to 277 days
Number of days subject survives Ultra Low Dose-Whole Lung Radiation Therapy, including hospital days and post discharge from hospital until lost to follow-up
long term follow, up to 277 days
Days of Supplemental Oxygen Therapy
Time Frame: length of hospital stay, up to day 47
To evaluate total supplemental oxygen therapy
length of hospital stay, up to day 47
Ventilator-free Days
Time Frame: length of subject hospitalization, up to day 47
number of days without mechanical ventilation
length of subject hospitalization, up to day 47
Oxygenation Index Post RT
Time Frame: length of hospitalization, up to 47 days

Oxygenation index until extubated, for up to 47 days. Oxygenation Index (OI) in medicine (OI = FiO2 x MAP x100/ PaO2) assesses severe lung injury, with higher numbers meaning worse function. This is expressed as a fraction, with no units and is not a percentage

A normal Oxygenation Index (OI) measures the severity of respiratory failure. The ratio is for a healthy peron is 25 and lower. Oxygenation Index values of 25-40 indicate high mortality,

Definitions: Mean Airway Pressure (MAP); FiO2 (Fraction of Inspired Oxygen) is the concentration or percentage of oxygen a patient breathes; PaO2 (Partial pressure of oxygen) is a measurement from an Arterial Blood Gas (ABG) test that shows the pressure of oxygen dissolved in your arterial blood
length of hospitalization, up to 47 days
Differences Between Ground Glass Opacities (GGO), Lung Infiltrates and Opacification Percentage
Time Frame: assessed at day 0, 7, 14, and 28 post radiation
Quantitate post-ULD-WLRT the baseline and Day 7, 14, and 28 CT chest findings ( total number of GGO, lung infiltrates and opacification) and the percentage of each chest finding (GGO, lung infiltrates and opacification) found in a CT scan image.
assessed at day 0, 7, 14, and 28 post radiation
Viral Titers at Days 0, 1 7, 14 and 28 Post RT
Time Frame: assessed at days 0, 1, 7, 14 and 28 days post radiation
Evaluate SARS-CoV2 viral titers at baseline and post Ultra Low Dose-Whole Lung Radiation Therapy (ULD-WLRT) at Day 0, 1, 7, 14, and 28
assessed at days 0, 1, 7, 14 and 28 days post radiation
Tolerability of Regimen
Time Frame: up to 9 months post radiation
Establish safety and tolerability using number of days of survival
up to 9 months post radiation

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Molecular Markers
Time Frame: assessed at days 0, 1, 7, 14, and 28
Molecular biomarker levels in COVID-19 patients upfront as well as after treatment with Ultra Low Dose-Whole Lung Radiation Therapy (ULD-WLRT) such as levels or inflammatory and DNA damage markers).
assessed at days 0, 1, 7, 14, and 28
Baseline Molecular Biomarkers
Time Frame: during hospitalization, on day 1 prior to radiation
Determine baseline molecular biomarkers that predict response to Ultra Low Dose-Whole Lung Radiation Therapy (ULD-WLRT) in COVID-19 patients.
during hospitalization, on day 1 prior to radiation
Molecular Biomarker Level
Time Frame: during hospitalization, on days 0, 1, 7, 14, and 28
Determine molecular biomarkers that change over the treatment course, correlating with disease status and resolution.
during hospitalization, on days 0, 1, 7, 14, and 28
Evaluate Treatment Plan Evaluation Using CBCT Images
Time Frame: day of radiation treatment
Retrospectively evaluate rapidly planned treatment using volumetric treatment plan evaluation based on Cone Beam CT (CBCT)
day of radiation treatment
Compare Imaging Data
Time Frame: up to 277 days post treatment
comparison of raw diagnostic and CBCT imaging data for machine-learning assessment of longitudinal progression in patients with COVID-19
up to 277 days post treatment
Compare Raw Imaging Data for Diagnosis
Time Frame: imaging prior to radiation
Collect raw imaging data for further evaluation of the potential for identification of COVID-19 in diagnostic scans
imaging prior to radiation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ohio State University

Investigators

  • Principal Investigator: Arnab Chakravarti, James Cancer Hospital, Department of Radiation Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 23, 2020

Primary Completion (Actual)

April 26, 2021

Study Completion (Actual)

April 26, 2021

Study Registration Dates

First Submitted

June 5, 2020

First Submitted That Met QC Criteria

June 9, 2020

First Posted (Actual)

June 11, 2020

Study Record Updates

Last Update Posted (Actual)

August 19, 2026

Last Update Submitted That Met QC Criteria

July 28, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VENTED

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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