Lung Irradiation for COVID-19 Pneumonia

• ClinicalTrials.gov Identifier: NCT04393948
• Recruitment Status: Recruiting
• First Posted: May 19, 2020
• Last Update Posted: June 25, 2020
• Sponsor: Brigham and Women's Hospital
• Information provided by (Responsible Party): David E. Kozono, Brigham and Women's Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
SARS-CoV 2	Radiation: Phase 1; Radiation: Phase 2	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of Low-Dose Single or Bilateral Whole Lung Irradiation for SARS-CoV-2 Pneumonia
• Estimated Study Start Date: June 2020
• Estimated Primary Completion Date: October 2020
• Estimated Study Completion Date: November 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Feasibility and safety of treating hospitalized patients with SARS-CoV-2 pneumonia with single or bilateral whole lung irradiation [ Time Frame: 4 days after randomization ]
   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
2. Phase 2: Proportion with clinical improvement on a 7-point ordinal scale on day 4 after randomization [ Time Frame: 4 days 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:

   1. Death
   2. Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO)
   3. Hospitalized, on non-invasive ventilation or high flow oxygen devices
   4. Hospitalized, requiring low flow supplemental oxygen
   5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
   6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care
   7. Not hospitalized

Secondary Outcome Measures :

1. Improvement or worsening on the 7-point ordinal scale over additional intervals [ Time Frame: Up to 30 days after randomization ]
2. Rate and duration of use of supplemental oxygen [ Time Frame: Up to 30 days after randomization ]
3. Rate and duration of fever > 38ºC [ Time Frame: Up to 30 days after randomization ]
4. Rate and duration of invasive mechanical ventilation [ Time Frame: Up to 30 days after randomization ]
5. Duration of hospitalization [ Time Frame: Up to 30 days after randomization ]
6. Proportion of participants with overall survival up to 30 days after randomization [ Time Frame: Up to 30 days after randomization ]
7. 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 [ Time Frame: Up to 30 days after randomization ]
8. Treatment-emergent adverse events [ Time Frame: Up to 30 days after randomization ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Thomas Johnson, MS; (617) 582-8977; tjohnson45@bwh.harvard.edu

Locations

United States, Massachusetts

Brigham and Women's Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Thomas Johnson, MS 617-582-8977 tjohnson45@bwh.harvard.edu

Sponsors and Collaborators

Brigham and Women's Hospital

Investigators

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

More Information

• Responsible Party: David E. Kozono, Associate Radiation Oncologist, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT04393948
• Other Study ID Numbers: 2020P001494
• First Posted: May 19, 2020
• Last Update Posted: June 25, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by David E. Kozono, Brigham and Women's Hospital:

SARS-CoV-2; Radiation Therapy; COVID-19

Additional relevant MeSH terms:

Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections