Radiation Eliminates Storming Cytokines and Unchecked Edema as a 1-Day Treatment for COVID-19 (RESCUE 1-19)

The RESCUE 1-19 Trial: Radiation Eliminates Storming Cytokines and Unchecked Edema as a 1-Day Treatment for COVID-19

This phase I/II trial studies low-dose radiation therapy as a focal anti-inflammatory treatment for patients with pneumonia or SARS associated with COVID-19 infection.

Study Overview

• Status: Terminated
• Conditions: Pneumonia; Coronavirus Infection in 2019 (COVID-19); Severe Acute Respiratory Syndrome (SARS) Pneumonia
• Intervention / Treatment: Radiation: Low Dose Radiation Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To compare treatment of COVID-19 between best supportive care plus provider's treatment choice versus best supportive care plus low-dose, whole-lung radiation therapy

OUTLINE:

Patients undergo 1 fraction of low-dose radiation therapy.

After completion of study treatment, patients are followed up at days 1-7, and 14 after last dose of intervention.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hosptial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have had a positive test confirming the diagnosis of COVID-19
• Have had clinical signs of severe acute respiratory syndrome or pneumonia (dyspnea, cough, with need for oxygen support at the time of enrollment)
• Have visible consolidations/ground glass opacities on chest x-ray or computed tomography
• Have received pre-intubation respiratory support or undergone endotracheal intubation and have been on ventilator support for no longer than 5 (five) calendar days prior to the schedule date of delivery of low-dose radiation therapy.
• 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:

• No use of disallowed medications 1 day prior to delivery of LDRT: Azithromycin, chloroquine, hydrochloroquine, COVID-targeted antiviral medications
• Pregnant and/or planned to be pregnant within in next 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supportive care (low-dose radiation therapy); Patients undergo 1 fraction of low-dose radiation therapy.	Radiation: Low Dose Radiation Therapy; Undergo low-dose radiation therapy; Other Names: Low Dose Radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of extubation (for intubated patients)	The rate will be reported, along with a two-sided 95% exact binomial confidence interval, using the Clopper-Pearson method. The observed extubation rate will be compared to the null rate of 20% using a two-sided binomial test. Statistical significance is assessed at the 0.05 level.	Screening up to 28 days after radiation therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical outcome - Temperature	Temperature in degrees (F)	Screening up to 28 days after radiation therapy
Clinical outcome - Heart Rate	Heart rate in beats per minutes	Screening up to 28 days after radiation therapy
Clinical outcome - Systolic blood pressure	Systolic blood pressure in mm Hg	Screening up to 28 days after radiation therapy
Clinical outcome - Oxygenation	Oxygen saturation in percentage	Screening up to 28 days after radiation therapy
Clinical outcome - Respirations	Respiratory rate in breaths per minute	Screening up to 28 days after radiation therapy
Clinical outcome - FiO2	FI02 in percentage	Screening up to 28 days after radiation therapy
Clinical outcome - PEEP	Positive end expiratory pressure (PEEP) in cm H20	Screening up to 28 days after radiation therapy
Clinical outcome - Tidal volume	Tidal volume in mL	Screening up to 28 days after radiation therapy
Clinical outcome - Intubation/Extubation events	Extubation/intubation events in percentage	Screening up to 28 days after radiation therapy
Clinical outcome - Overall survival	Survival in percentage	Screening up to 28 days after radiation therapy
Radiographic outcome - Chest xray	Serial chest x-rays categorized using published scale into ordinal ranks 1-5 for SARS.	Screening up to 28 days after radiation therapy
Radiographic outcome - CT can	CT scans with volume of consolidation measured in cubic centimeters.	Screening up to 28 days after radiation therapy
Serologic outcome - WBC	White blood cell count in cell count x 10^3/mcL	Screening up to 28 days after radiation therapy
Serologic outcome - Hgb	Hemoglobin in gm/dL	Screening up to 28 days after radiation therapy
Serologic outcome - Procalcitonin	Procalcitonin in ng/mL	Screening up to 28 days after radiation therapy
Serologic outcome - ANC	Absolute neutrophil count in cell count x 10^3/mcL	Screening up to 28 days after radiation therapy
Serologic outcome - Creatine kinase	Creatine kinase in units/L	Screening up to 28 days after radiation therapy
Serologic outcome - Myoglobin	Myoglobin in ng/mL	Screening up to 28 days after radiation therapy
Serologic outcome - Albumin	Albumin in gm/dL	Screening up to 28 days after radiation therapy
Serologic outcome - PT/PTT	Coagulation pathway time in seconds	Screening up to 28 days after radiation therapy
Serologic outcome - D-Dimer	D-Dimer in ng/mL	Screening up to 28 days after radiation therapy
Serologic outcome - GGT	Gamma-glutamyl transferase in units/L	Screening up to 28 days after radiation therapy
Serologic outcome -Triglycerides	Trygliciericdes in mg/dL	Screening up to 28 days after radiation therapy
Serologic outcome -Ferritin	Ferritin in ng/mL	Screening up to 28 days after radiation therapy
Serologic outcome -Fibrinogen	Fibrinogen in mg/dL	Screening up to 28 days after radiation therapy
Serologic Immune markers flow cytometry	Immune marker flow cytometry (refractive index)	Screening up to 28 days after radiation therapy
Serologic outcome -Bilirubin	Bilirubin in mg/dL	Screening up to 28 days after radiation therapy
Serologic outcome - LDH	Lactate Dehydrogenase in units/L	Screening up to 28 days after radiation therapy
Serologic outcome - Creatinine	Creatinine in mg/dL	Screening up to 28 days after radiation therapy
Serologic outcome - EGFR	Estimated Glomerular Filtration Rate in mL/min/m2	Screening up to 28 days after radiation therapy
Serologic outcome - CRP	C-Reactive Protein in mg/L	Screening up to 28 days after radiation therapy
Serologic outcome - ALT	Alanine Aminotransferase in units/L	Screening up to 28 days after radiation therapy
Serologic outcome - AST	Asparatate Aminotransferase in units/L	Screening up to 28 days after radiation therapy
Serologic outcome - Troponin-I	Troponin-I in ng/mL	Screening up to 28 days after radiation therapy
Serologic outcome - BNP	B-Natriuretic Peptid in pg/mL	Screening up to 28 days after radiation therapy
Serologic outcome - Blood Gases pH	pH (no unit)	Screening up to 28 days after radiation therapy
Serologic outcome - Blood Gases pO2	pressure of O2 in mm Hg	Screening up to 28 days after radiation therapy
Serologic outcome - Blood Gases pCO2	pressure of CO2 in mm Hg	Screening up to 28 days after radiation therapy
Serologic outcome - Lactic Acid	Lactic Acid in mmol/L	Screening up to 28 days after radiation therapy
Serologic outcome - IL-6	Interleukin-6 in pg/mL	Screening up to 28 days after radiation therapy
Serologic outcome - Potassium	Potassium in mmol/L	Screening up to 28 days after radiation therapy

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Hess CB, Eng TY, Nasti TH, Dhere VR, Kleber TJ, Switchenko JM, Weinberg BD, Rouphael N, Tian S, Rudra S, Taverna LS, Daisson AP, Ahmed R, Khan MK. Whole-lung low-dose radiation therapy (LD-RT) for non-intubated oxygen-dependent patients with COVID-19-related pneumonia receiving dexamethasone and/or remdesevir. Radiother Oncol. 2021 Dec;165:20-31. doi: 10.1016/j.radonc.2021.10.003. Epub 2021 Oct 13.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2020
• Primary Completion (Actual): March 11, 2022
• Study Completion (Actual): March 11, 2022

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 28, 2020
• First Posted (Actual): April 29, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Pneumonia
• Other Study ID Numbers: STUDY00000476; P30CA138292 (U.S. NIH Grant/Contract); NCI-2020-02676 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RAD5002-20 (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

No

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