Best Supportive Care With or Without Low Dose Whole Lung Radiation Therapy for the Treatment of COVID-19 (RESCUE1-19)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Severe Acute Respiratory Syndrome; Pneumonia; Symptomatic COVID-19 Infection Laboratory-Confirmed
• Intervention / Treatment: Other: Best Practice; Radiation: Low Dose Radiation Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mohammad K Khan, MD, PhD; Phone Number: 404-778-3473; Email: drkhurram2000@gmail.com
• Study Contact Backup: Name: Clayton B Hess, MD, MPH; Phone Number: 404-616-3947; Email: cbhess@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mohammad K Khan, MD, PhD, Emory University Hospital/Winship Cancer Institute

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Interim Results from the phase 1, 2 pilot safety trial of LD-RT for COVID
• Article on Forbes

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2020
• Primary Completion (Actual): October 19, 2022
• Study Completion (Estimated): May 30, 2024

Study Registration Dates

• First Submitted: June 12, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; Radiotherapy; anti-inflammatory; cytokine storm; low dose radiotherapy
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Occupational Diseases; Severe Acute Respiratory Syndrome; COVID-19; Laboratory Infection
• Other Study ID Numbers: STUDY00000781; P30CA138292 (U.S. NIH Grant/Contract); NCI-2020-04061 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RAD5049-20 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Results of the trial and not individual patient data will be shared. The study protocol, consent, and investigator's brochure will be available. The statistical plan is incorporated into the protocol, along with inclusion and exclusion criteria.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes