Lung Irradiation for COVID-19 Pneumonia
Primary Purpose
SARS-CoV 2
Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Phase 1
Phase 1
Phase 2
Phase 2
Phase 2
Sponsored by
About this trial
This is an interventional treatment trial for SARS-CoV 2 focused on measuring SARS-CoV-2, Radiation Therapy, COVID-19
Eligibility 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
Sites / Locations
- Brigham and Women's Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
No irradiation
100 cGy single lung irradiation
100 cGy bilateral lung irradiation
Arm Description
100 cGy single lung radiation
100 cGy bilateral lung radiation
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
Improvement or worsening on the 7-point ordinal scale over additional intervals
Rate and duration of use of supplemental oxygen
Rate and duration of fever > 38ºC
Rate and duration of invasive mechanical ventilation
Duration of hospitalization
Proportion of participants with overall survival 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
Treatment-emergent adverse events
Full Information
NCT ID
NCT04393948
First Posted
May 15, 2020
Last Updated
January 21, 2022
Sponsor
Brigham and Women's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04393948
Brief Title
Lung Irradiation for COVID-19 Pneumonia
Official Title
Pilot Study of Low-Dose Single or Bilateral Whole Lung Irradiation for SARS-CoV-2 Pneumonia
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of accrual
Study Start Date
June 19, 2020 (Actual)
Primary Completion Date
June 2021 (Anticipated)
Study Completion Date
September 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SARS-CoV 2
Keywords
SARS-CoV-2, Radiation Therapy, COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
No irradiation
Arm Type
Experimental
Arm Title
100 cGy single lung irradiation
Arm Type
Experimental
Arm Description
100 cGy single lung radiation
Arm Title
100 cGy bilateral lung irradiation
Arm Type
Experimental
Arm Description
100 cGy bilateral lung radiation
Intervention Type
Radiation
Intervention Name(s)
Phase 1
Intervention Description
Dose Level 1 - 100 cGy irradiation to a single (right-sided) lung using 6 MV photons delivered using a clinical linear accelerator
Intervention Type
Radiation
Intervention Name(s)
Phase 1
Intervention Description
Dose Level 2 - 100 cGy irradiation to both lungs using 6 MV photons delivered using a clinical linear accelerator
Intervention Type
Radiation
Intervention Name(s)
Phase 2
Intervention Description
Arm A - No irradiation
Intervention Type
Radiation
Intervention Name(s)
Phase 2
Intervention Description
Arm B - 100 cGy irradiation to a single (right-sided) lung using 6 MV photons delivered using a clinical linear accelerator
Intervention Type
Radiation
Intervention Name(s)
Phase 2
Intervention Description
Arm C - 100 cGy irradiation to both lungs using 6 MV photons delivered using a clinical linear accelerator
Primary Outcome Measure Information:
Title
Phase 1: Feasibility and safety of treating hospitalized patients with SARS-CoV-2 pneumonia with single or bilateral whole lung irradiation
Description
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
Time Frame
4 days after randomization
Title
Phase 2: Proportion with clinical improvement on a 7-point ordinal scale on day 4 after randomization
Description
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
Time Frame
4 days after randomization
Secondary Outcome Measure Information:
Title
Improvement or worsening on the 7-point ordinal scale over additional intervals
Time Frame
Up to 30 days after randomization
Title
Rate and duration of use of supplemental oxygen
Time Frame
Up to 30 days after randomization
Title
Rate and duration of fever > 38ºC
Time Frame
Up to 30 days after randomization
Title
Rate and duration of invasive mechanical ventilation
Time Frame
Up to 30 days after randomization
Title
Duration of hospitalization
Time Frame
Up to 30 days after randomization
Title
Proportion of participants with overall survival up to 30 days after randomization
Time Frame
Up to 30 days after randomization
Title
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
Title
Treatment-emergent adverse events
Time Frame
Up to 30 days after randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Kozono, MD, PhD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Lung Irradiation for COVID-19 Pneumonia
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