Best Supportive Care With or Without Low Dose Whole Lung Radiation Therapy for the Treatment of COVID-19

Study Overview
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Brief Summary
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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
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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.

Official Title
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Radiation Eliminates Storming Cytokines and Unchecked Edema as a 1-Day Treatment for COVID-19 (RESCUE 1-19): A Randomized Phase III Trial of Best Supportive Care Plus Provider's Choice of Pharmaceutical Treatment With or Without Whole Lung Low-Dose Radiation Therapy (LD-RT) in Hospitalized Patients With COVID-19

Conditions
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Pneumonia, Severe Acute Respiratory Syndrome, Symptomatic COVID-19 Infection Laboratory-Confirmed

Intervention / Treatment
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* Other: Best Practice
* Radiation: Low Dose Radiation Therapy


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria: Pregnant and/or planned to be pregnant within in next 6 months Age 49 or younger at time of enrollment Prior inpatient hospitalization for COVID-19 (prior emergency department [ED] visits are not an exclusion criteria) Prior enrollment on a separate COVID-19-related therapeutric trial (subsequent co-enrollment is permitted for patinets randomized to the control arm). Notably, concurrent use of COVID-directed therapies is no longer an exclusion criteria for this trial. This includes azithromycin, dexamethasone, remdesevir, convalescent plasma, or any other COVIDdirected drug therapy.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (physician choice)<br>Patients get best supportive care + physician choice of treatment | Other: Best Practice<br>* Receive standard of care<br>* Other names: standard therapy;|
| Experimental: Arm II (LDRT)<br>Patients receive best supportive care + low dose RT (whole lung) | Radiation: Low Dose Radiation Therapy<br>* Undergo LDRT<br>* Other names: Low Dose Radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical recovery | Will be measured by improvements on oxygenation need prior to intervention compared with after intervention and/or hospital discharge. | Up to follow-up day 14 after study start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from ICU admission | The rates from both cohort will be reported. | Up to follow-up day 14 after study start; This may be extended up to 28 days after preplanned interim analysis. | 
| Temperature | Temperature in degrees (F) | Up to follow-up day 14 after study start | 
| Heart rate | Heart rate in beats per minutes | Up to follow-up day 14 after study start | 
| Systolic Blood pressure | Systolic blood pressure in mm Hg | Up to follow-up day 14 after study start | 
| Oxygen saturation | Oxygen saturation in percentage | Up to follow-up day 14 after study start | 
| Supplemental oxygenation need | Oxygen saturation in percentage | Up to follow-up day 14 after study start | 
| Respiratory rate | Respiratory rate in breaths per minute. | Up to follow-up day 14 after study start | 
| Glasgow Comma Scale from minimum of 3 to maximum of 15. | Pre and post intervention; Minimum of 3 (poor) to best (15) | Up to follow-up day 14 after study start | 
| Performance status | Easter Cooperative Oncology Group (ECOG) Performance Status Scale from 0-5; 0 being best; 5 being dead; | Up to follow-up day 14 after study start | 
| Survival | Survival in percentage | Up to follow-up day 14 after study start; This may be extended to 28 days after preplanned interim analysis. | 
| Serial chest x-rays severe acute respiratory syndrome (SARS) scoring | Serial chest x-rays categorized using published scale into ordinal ranks 1-5 for SARS. | Up to follow-up day 14 after study start; | 
| Changes on computed tomography (CT) scans pre and post RT | CT scans with volume of consolidation measured in cubic centimeters. | Baseline up to follow-up day 14 after study start | 
| CRP | C-Reactive Protein in mg/L | Up to follow-up day 14 after study start | 
| Serum chemistry + complete blood cell (CBC) with differential | Will be summarized descriptively. | Up to follow-up day 14 after study start | 
| Blood gases pH(when available) | pH (no unit) | Up to follow-up day 14 after study start | 
| Albumin | Albumin in gm/dL | Up to follow-up day 14 after study start | 
| Procalcitonin | Procalcitonin in ng/mL | Up to follow-up day 14 after study start | 
| Aspartate aminotransferase (AST) | Asparatate Aminotransferase in units/L | Up to follow-up day 14 after study start | 
| Creatine kinase | Creatinine in mg/dL | Up to follow-up day 14 after study start | 
| Prothrombin time (PT)/partial thromboplastin time (PTT) | Coagulation pathway time in seconds | Up to follow-up day 14 after study start | 
| Troponin | Troponin-I in ng/mL | Up to follow-up day 14 after study start | 
| Lactate | Lactic Acid in mmol/L | Up to follow-up day 14 after study start | 
| NT-pBNP (cardiac injury) | B-Natriuretic Peptid in pg/mL | Up to follow-up day 14 after study start | 
| Gamma-glutamyl transferase (GGT) | Gamma-glutamyl transferase in units/L | Up to follow-up day 14 after study start | 
| Triglycerides | Trygliciericdes in mg/dL | Up to follow-up day 14 after study start | 
| Fibrinogen | Fibrinogen in mg/dL | Up to follow-up day 14 after study start | 
| Changes in CD8 T cells | Will be summarized descriptively. | Up to follow-up day 14 after study start | 
| Changes in CD4 T cells | Will be summarized descriptively. | Up to follow-up day 14 after study start | 
| Changes in serum antibodies against COVID-19 epitope | Will be summarized descriptively. | Up to follow-up day 14 after study start | 
| LDH | Lactate Dehydrogenase in units/L | Up to follow-up day 14 after study start | 
| D-Dimer | D-Dimer in ng/mL | Up to follow-up day 14 after study start | 
| IL-6 | Interleukin-6 in pg/mL | Up to follow-up day 14 after study start | 
| Myoglobin | Myoglobin in ng/mL | Up to follow-up day 14 after study start | 
| Potassium | Potassium in mmol/L | Up to follow-up day 14 after study start | 
| Ferritin | Ferritin in ng/mL | Up to follow-up day 14 after study start | 
| ALT | Alanine Aminotransferase in units/L | Up to follow-up day 14 after study start | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Radiotherapy, low dose radiotherapy, anti-inflammatory, cytokine storm