COVID-19
Conditions
Keywords
ventilator, radiation
Brief summary
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.
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.
Interventions
RADIATIONRadiation 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.
Sponsors
Ohio State University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality Rate of Subjects Treated With Whole Lung Low-dose Radiation. | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Compare Total Hospital Stay and Length of Hospital Stay After Post Radiation Dose | Until subject discharged for any reason, up to day 47 | number of days hospitalized before and after radiation |
| Evaluate Total and Post-ULD-WLRT ICU Length of Stay | Until subject discharged for any reason, up to day 47 | Number of days in ICU after receiving radiation therapy |
| Number of Days Alive After RT in Days | 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 |
| Days of Supplemental Oxygen Therapy | length of hospital stay, up to day 47 | To evaluate total supplemental oxygen therapy |
| Ventilator-free Days | length of subject hospitalization, up to day 47 | number of days without mechanical ventilation |
| Oxygenation Index Post RT | 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 |
| Differences Between Ground Glass Opacities (GGO), Lung Infiltrates and Opacification Percentage | 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. |
| Viral Titers at Days 0, 1 7, 14 and 28 Post RT | 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 |
| Tolerability of Regimen | up to 9 months post radiation | Establish safety and tolerability using number of days of survival |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORArnab Chakravarti
James Cancer Hospital, Department of Radiation Oncology
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
None listed