Clinical trial NCT04433949: Best Supportive Care With or Without Low Dose Whole Lung Radiation Therapy for the Treatment of COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Pneumonia
Severe Acute Respiratory Syndrome
Symptomatic COVID-19 Infection Laboratory-Confirmed
Keywords: Radiotherapy
COVID-19
low dose radiotherapy
anti-inflammatory
cytokine storm
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-06-16
Enrollment: 14
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to clinical recovery
timeFrame: Up to follow-up day 14 after study start
Secondary outcomes:
measure: Freedom from ICU admission
timeFrame: Up to follow-up day 14 after study start; This may be extended up to 28 days after preplanned interim analysis.
measure: Temperature
timeFrame: Up to follow-up day 14 after study start
measure: Heart rate
timeFrame: Up to follow-up day 14 after study start
measure: Systolic Blood pressure
timeFrame: Up to follow-up day 14 after study start
measure: Oxygen saturation
timeFrame: Up to follow-up day 14 after study start
measure: Supplemental oxygenation need
timeFrame: Up to follow-up day 14 after study start
measure: Respiratory rate
timeFrame: Up to follow-up day 14 after study start
measure: Glasgow Comma Scale from minimum of 3 to maximum of 15.
timeFrame: Up to follow-up day 14 after study start
measure: Performance status
timeFrame: Up to follow-up day 14 after study start
measure: Survival
timeFrame: Up to follow-up day 14 after study start; This may be extended to 28 days after preplanned interim analysis.
measure: Serial chest x-rays severe acute respiratory syndrome (SARS) scoring
timeFrame: Up to follow-up day 14 after study start;
measure: Changes on computed tomography (CT) scans pre and post RT
timeFrame: Baseline up to follow-up day 14 after study start
measure: CRP
timeFrame: Up to follow-up day 14 after study start
measure: Serum chemistry + complete blood cell (CBC) with differential
timeFrame: Up to follow-up day 14 after study start
measure: Blood gases pH(when available)
timeFrame: Up to follow-up day 14 after study start
measure: Albumin
timeFrame: Up to follow-up day 14 after study start
measure: Procalcitonin
timeFrame: Up to follow-up day 14 after study start
measure: Aspartate aminotransferase (AST)
timeFrame: Up to follow-up day 14 after study start
measure: Creatine kinase
timeFrame: Up to follow-up day 14 after study start
measure: Prothrombin time (PT)/partial thromboplastin time (PTT)
timeFrame: Up to follow-up day 14 after study start
measure: Troponin
timeFrame: Up to follow-up day 14 after study start
measure: Lactate
timeFrame: Up to follow-up day 14 after study start
measure: NT-pBNP (cardiac injury)
timeFrame: Up to follow-up day 14 after study start
measure: Gamma-glutamyl transferase (GGT)
timeFrame: Up to follow-up day 14 after study start
measure: Triglycerides
timeFrame: Up to follow-up day 14 after study start
measure: Fibrinogen
timeFrame: Up to follow-up day 14 after study start
measure: Changes in CD8 T cells
timeFrame: Up to follow-up day 14 after study start
measure: Changes in CD4 T cells
timeFrame: Up to follow-up day 14 after study start
measure: Changes in serum antibodies against COVID-19 epitope
timeFrame: Up to follow-up day 14 after study start
measure: LDH
timeFrame: Up to follow-up day 14 after study start
measure: D-Dimer
timeFrame: Up to follow-up day 14 after study start
measure: IL-6
timeFrame: Up to follow-up day 14 after study start
measure: Myoglobin
timeFrame: Up to follow-up day 14 after study start
measure: Potassium
timeFrame: Up to follow-up day 14 after study start
measure: Ferritin
timeFrame: Up to follow-up day 14 after study start
measure: ALT
timeFrame: Up to follow-up day 14 after study start
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University Hospital/Winship Cancer Institute
name: Mohammad K Khan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lara PC, Burgos J, Macias D. Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment. Clin Transl Radiat Oncol. 2020 Apr 25;23:27-29. doi: 10.1016/j.ctro.2020.04.006. eCollection 2020 Jul.
citation: Dhawan G, Kapoor R, Dhawan R, Singh R, Monga B, Giordano J, Calabrese EJ. Low dose radiation therapy as a potential life saving treatment for COVID-19-induced acute respiratory distress syndrome (ARDS). Radiother Oncol. 2020 Jun;147:212-216. doi: 10.1016/j.radonc.2020.05.002. Epub 2020 May 8.