Lung Irradiation for COVID-19 Pneumonia

Pilot Study of Low-Dose Single or Bilateral Whole Lung Irradiation for SARS-CoV-2 Pneumonia

In this research study the investigators want to learn more about the potential benefit of radiation to the lung to improve the health of patients who are hospitalized with Coronavirus-19 (COVID-19) due to infection with a virus called SARS-CoV-2. This infection causes inflammation of the lung, which can make it difficult to breathe. As a result, patients may need supplemental oxygen or be placed on a ventilator. The investigators believe that low dose radiation therapy to the lung may reduce this inflammation and increase the likelihood that patients will need less oxygen support such as ventilation or supplemental oxygen, or be discharged from the hospital in fewer days, compared to without radiation therapy. The amount of radiation is much lower than what is typically used to treat other conditions such as cancer, although it is higher than the dose used for routine medical imaging.

Study Overview

• Status: Withdrawn
• Conditions: SARS-CoV 2
• Intervention / Treatment: Radiation: Phase 2; Radiation: Phase 2; Radiation: Phase 2; Radiation: Phase 1; Radiation: Phase 1

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• Diagnosis of SARS-CoV-2 infection by RT-PCR or another approved laboratory test ≤ 3 days before enrollment or ≤ 14 days before enrollment with progressive disease suggestive of ongoing SARS-CoV-2 infection; retesting allowed
• Current hospitalization for ≤ 14 days with SARS-CoV-2 infection at the time of enrollment
• Use of supplemental oxygen or oxygen saturation ≤ 94% on room air
• Age ≥ 40
• May receive antiviral medication (e.g., remdesivir, lopinavir/ritonavir, oseltamivir, favipiravir), antibiotics (e.g., azithromycin), chloroquine, hydroxychloroquine, corticosteroids, statins, anticoagulation, antiplatelet agents (e.g., aspirin) and/or convalescent plasma from recovered individuals off study and/or on study if permitted by the other protocol

Exclusion criteria

• Prior or planned treatment with interleukin inhibitors (e.g., tocilizumab, canakinumab, sarilumab) or TNF-α inhibitors within 14 days of enrollment
• Prior lobectomy or pneumonectomy
• Prior thoracic radiotherapy with cumulative lung V20 > 15% to either lung within 1 year of enrollment, or any radiotherapy resulting in a maximum lung dose of 100 cGy or higher within 14 days of enrollment
• Prior chemotherapy or other systemic therapy with potential for pulmonary toxicity or radiosensitization within 14 days or 5 half-lives, whichever is greater, of enrollment, e.g., bleomycin or gemcitabine
• Prior cancer immunotherapy with an immune checkpoint inhibitor within 60 days of enrollment
• Severe pre-existing heart disease, e.g., New York Heart Association (NYHA) functional class ≥ 3 congestive heart failure
• History of bone marrow or solid organ transplantation
• Known history of autoimmune collagen vascular disease, e.g., scleroderma
• Known hereditary syndrome with increased sensitivity to ionizing radiation, e.g., ataxia-telangiectasia or Fanconi anemia
• Pregnancy
• Inability to be positioned supine and flat for radiation planning and delivery
• Inability to provide informed consent or lack of an authorized representative who can provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: No irradiation	Radiation: Phase 2; Arm A - No irradiation; Radiation: Phase 2; Arm B - 100 cGy irradiation to a single (right-sided) lung using 6 MV photons delivered using a clinical linear accelerator; Radiation: Phase 2; Arm C - 100 cGy irradiation to both lungs using 6 MV photons delivered using a clinical linear accelerator
Experimental: 100 cGy single lung irradiation; 100 cGy single lung radiation	Radiation: Phase 2; Arm A - No irradiation; Radiation: Phase 2; Arm B - 100 cGy irradiation to a single (right-sided) lung using 6 MV photons delivered using a clinical linear accelerator; Radiation: Phase 2; Arm C - 100 cGy irradiation to both lungs using 6 MV photons delivered using a clinical linear accelerator; Radiation: Phase 1; Dose Level 1 - 100 cGy irradiation to a single (right-sided) lung using 6 MV photons delivered using a clinical linear accelerator; Radiation: Phase 1; Dose Level 2 - 100 cGy irradiation to both lungs using 6 MV photons delivered using a clinical linear accelerator
Experimental: 100 cGy bilateral lung irradiation; 100 cGy bilateral lung radiation	Radiation: Phase 2; Arm A - No irradiation; Radiation: Phase 2; Arm B - 100 cGy irradiation to a single (right-sided) lung using 6 MV photons delivered using a clinical linear accelerator; Radiation: Phase 2; Arm C - 100 cGy irradiation to both lungs using 6 MV photons delivered using a clinical linear accelerator; Radiation: Phase 1; Dose Level 1 - 100 cGy irradiation to a single (right-sided) lung using 6 MV photons delivered using a clinical linear accelerator; Radiation: Phase 1; Dose Level 2 - 100 cGy irradiation to both lungs using 6 MV photons delivered using a clinical linear accelerator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Feasibility and safety of treating hospitalized patients with SARS-CoV-2 pneumonia with single or bilateral whole lung irradiation	Subjects will be treated with 100 cGy irradiation to a single (right-sided) lung (dose level 1) or 100 cGy irradiation to both lungs (dose level 2) following a 3 + 3 dose escalation scheme	4 days after randomization
Phase 2: Proportion with clinical improvement on a 7-point ordinal scale on day 4 after randomization	The ordinal scale is an assessment of the clinical status on a given day. Each day, the worst (lowest) score from the previous day will be recorded as the score for that previous day. The scale is as follows: Death; Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring low flow supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; Not hospitalized	4 days after randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
Improvement or worsening on the 7-point ordinal scale over additional intervals	Up to 30 days after randomization
Rate and duration of use of supplemental oxygen	Up to 30 days after randomization
Rate and duration of fever > 38ºC	Up to 30 days after randomization
Rate and duration of invasive mechanical ventilation	Up to 30 days after randomization
Duration of hospitalization	Up to 30 days after randomization
Proportion of participants with overall survival up to 30 days after randomization	Up to 30 days after randomization
Improvement in radiographic findings related to infection/inflammation; comparisons include on study versus baseline scans and irradiated vs. unirradiated lung in subjects randomized to receive single lung irradiation	Up to 30 days after randomization
Treatment-emergent adverse events	Up to 30 days after randomization

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: David Kozono, MD, PhD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2020
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: May 15, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): February 4, 2022
• Last Update Submitted That Met QC Criteria: January 21, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Radiation Therapy
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: 2020P001494

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