Low doses of radiation in the form of chest X-rays have been used to treat people withpneumonia. This treatment was found to be effective by reducing inflammation and withminimal side effects. However, it was an expensive treatment and was eventually replacedwith less costly treatments such as antibiotics. Radiation has also been shown in someanimal experiments to reduce some types of inflammation.Some patients diagnosed with COVID-19 pneumonia will experience worsening disease, whichcan become very serious, requiring the use of a ventilator. This is caused byinflammation in the lung from the virus and the immune system. For this study, the x-raygiven is called radiation therapy. Radiation therapy uses high-energy X-ray beams from alarge machine to target the lungs and reduce inflammation. Usually, it is given at muchhigher doses to treat cancers.The purpose of this study is to find out if adding a single treatment of low-dose x-raysto the lungs might reduce the amount of inflammation in the lungs from a COVID-19infection, which could help a patient to breathe without use of a ventilator.
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.
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 Name: Linear accelerator,x-rays,LINAC
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
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States
Investigator: Arnab Chakravarti, MD
Contact: 614-293-8415
Arnab.Chakravarti@osumc.edu
Investigator: Arnab Chakravarti, MD
Arnab Chakravarti
614-293-0672
Arnab.Chakravarti@osumc.edu
Kimberly Mahler
614-685-4247
kimberly.mahler@osumc.edu
Arnab Chakravarti, Principal Investigator
James Cancer Hospital, Department of Radiation Oncology