Pneumonia, Severe Acute Respiratory Syndrome, Symptomatic COVID-19 Infection Laboratory-Confirmed
Conditions
Keywords
Radiotherapy, COVID-19, low dose radiotherapy, anti-inflammatory, cytokine storm
Brief summary
This phase III trial compares low dose whole lung radiation therapy to best supportive care plus physicians choice in treating patients with COVID-19 infection. Low dose whole lung radiation therapy may work better than the current best supportive care and physician's choice in improving patients' clinical status, the radiographic appearance of their lungs, or their laboratory blood tests.
Detailed description
PRIMARY OBJECTIVE: I. Intubation-free survival (IFS) and (2) time to clinical recovery (TTCR) based on weaning off supplementary oxygenation or hospital discharge in COVID 19 patients. SECONDARY OBJECTIVES: I. To investigate (1) other clinical, (2) radiographic, (3) serologic markers, and (4) immune marker response to best supportive care plus provider's choice of pharmaceutical treatment either with or without whole-lung LD-RT II. Secondary clinical improvements will look at time to hospital discharge, prevention of ICU admissions, and overall survival. OUTLINE: Patients are blindly randomized to 1 of 2 arms. ARM I: Patients receive best supportive care plus physician choice of treatment ARM II: Patients receive best supportive care plus LDRT (experimental arm). After completion of study, patients are followed up for 14 days.
Interventions
OTHERBest Practice
Receive standard of care
RADIATIONLow Dose Radiation Therapy
Undergo LDRT
Sponsors
National Cancer Institute (NCI)
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be age 50 or over; Not pregnant (will undergo pregnancy testing if below age 55); * Have had a positive PCR-based test confirming the diagnosis of COVID-19 within 5 days (+/-2 day)of study enrollment\* * Have had clinical signs of severe acute respiratory syndrome or pneumonia (ie. dyspnea, cough,fever) that primary team feels like patient needs rescuing with LD-RT.\*\* * Have visible bilateral consolidations/ground glass opacities on chest imaging * Require supplemental oxygen at the time of enrollment, defined by inability to wean from supplemental oxygen within 24 hours prior to enrollment. * Not require intubation within 12 hours of randomization (ie, not screen fail). Intubation after enrollment but within 12 hours of randomization will be defined as a screen failure for both the LD-RT and control cohorts. * Be enrolled within 5 days (+/- 2) of first hospitalization for COVID-19. Prior hospitalization for COVID-19 will be an
Exclusion criteria
(prior ED visits are permissible). * Willingness and ability of the subject to comply with scheduled visits, protocol-specified laboratory tests, other study procedures, and study restrictions * Evidence of a signed informed consent/assent indicating that the subject is aware of the infectious nature of the disease and has been informed of the procedures to be followed, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to clinical recovery | Up to follow-up day 14 after study start | Will be measured by improvements on oxygenation need prior to intervention compared with after intervention and/or hospital discharge. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Temperature | Up to follow-up day 14 after study start | Temperature in degrees (F) |
| Heart rate | Up to follow-up day 14 after study start | Heart rate in beats per minutes |
| Systolic Blood pressure | Up to follow-up day 14 after study start | Systolic blood pressure in mm Hg |
| Oxygen saturation | Up to follow-up day 14 after study start | Oxygen saturation in percentage |
| Supplemental oxygenation need | Up to follow-up day 14 after study start | Oxygen saturation in percentage |
| Respiratory rate | Up to follow-up day 14 after study start | Respiratory rate in breaths per minute. |
| Glasgow Comma Scale from minimum of 3 to maximum of 15. | Up to follow-up day 14 after study start | Pre and post intervention; Minimum of 3 (poor) to best (15) |
| Performance status | Up to follow-up day 14 after study start | Easter Cooperative Oncology Group (ECOG) Performance Status Scale from 0-5; 0 being best; 5 being dead; |
| Survival | Up to follow-up day 14 after study start; This may be extended to 28 days after preplanned interim analysis. | Survival in percentage |
| Serial chest x-rays severe acute respiratory syndrome (SARS) scoring | Up to follow-up day 14 after study start; | Serial chest x-rays categorized using published scale into ordinal ranks 1-5 for SARS. |
| Changes on computed tomography (CT) scans pre and post RT | Baseline up to follow-up day 14 after study start | CT scans with volume of consolidation measured in cubic centimeters. |
| CRP | Up to follow-up day 14 after study start | C-Reactive Protein in mg/L |
| Serum chemistry + complete blood cell (CBC) with differential | Up to follow-up day 14 after study start | Will be summarized descriptively. |
| Blood gases pH(when available) | Up to follow-up day 14 after study start | pH (no unit) |
| Albumin | Up to follow-up day 14 after study start | Albumin in gm/dL |
| Procalcitonin | Up to follow-up day 14 after study start | Procalcitonin in ng/mL |
| Aspartate aminotransferase (AST) | Up to follow-up day 14 after study start | Asparatate Aminotransferase in units/L |
| Freedom from ICU admission | Up to follow-up day 14 after study start; This may be extended up to 28 days after preplanned interim analysis. | The rates from both cohort will be reported. |
| Prothrombin time (PT)/partial thromboplastin time (PTT) | Up to follow-up day 14 after study start | Coagulation pathway time in seconds |
| Troponin | Up to follow-up day 14 after study start | Troponin-I in ng/mL |
| Lactate | Up to follow-up day 14 after study start | Lactic Acid in mmol/L |
| NT-pBNP (cardiac injury) | Up to follow-up day 14 after study start | B-Natriuretic Peptid in pg/mL |
| Gamma-glutamyl transferase (GGT) | Up to follow-up day 14 after study start | Gamma-glutamyl transferase in units/L |
| Triglycerides | Up to follow-up day 14 after study start | Trygliciericdes in mg/dL |
| Fibrinogen | Up to follow-up day 14 after study start | Fibrinogen in mg/dL |
| Changes in CD8 T cells | Up to follow-up day 14 after study start | Will be summarized descriptively. |
| Changes in CD4 T cells | Up to follow-up day 14 after study start | Will be summarized descriptively. |
| Changes in serum antibodies against COVID-19 epitope | Up to follow-up day 14 after study start | Will be summarized descriptively. |
| LDH | Up to follow-up day 14 after study start | Lactate Dehydrogenase in units/L |
| D-Dimer | Up to follow-up day 14 after study start | D-Dimer in ng/mL |
| IL-6 | Up to follow-up day 14 after study start | Interleukin-6 in pg/mL |
| Myoglobin | Up to follow-up day 14 after study start | Myoglobin in ng/mL |
| Potassium | Up to follow-up day 14 after study start | Potassium in mmol/L |
| Ferritin | Up to follow-up day 14 after study start | Ferritin in ng/mL |
| ALT | Up to follow-up day 14 after study start | Alanine Aminotransferase in units/L |
| Creatine kinase | Up to follow-up day 14 after study start | Creatinine in mg/dL |
Countries
United States
Outcome results
None listed