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

Pneumonia Clinical Trial

— RESCUE1-19  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04433949
• Other study ID #: STUDY00000781
• Secondary ID: NCI-2020-04061RA
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 23, 2020
• Est. completion date: May 30, 2024

Study information

• Verified date: August 2023
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 14
• Est. completion date: May 30, 2024
• Est. primary completion date: October 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Other:
• Best Practice
Receive standard of care

Radiation:
• Low Dose Radiation Therapy
Undergo LDRT

Locations

Country	Name	City	State
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	Temperature	Temperature in degrees (F)	Up to follow-up day 14 after study start
Secondary	Heart rate	Heart rate in beats per minutes	Up to follow-up day 14 after study start
Secondary	Systolic Blood pressure	Systolic blood pressure in mm Hg	Up to follow-up day 14 after study start
Secondary	Oxygen saturation	Oxygen saturation in percentage	Up to follow-up day 14 after study start
Secondary	Supplemental oxygenation need	Oxygen saturation in percentage	Up to follow-up day 14 after study start
Secondary	Respiratory rate	Respiratory rate in breaths per minute.	Up to follow-up day 14 after study start
Secondary	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
Secondary	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
Secondary	Survival	Survival in percentage	Up to follow-up day 14 after study start; This may be extended to 28 days after preplanned interim analysis.
Secondary	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;
Secondary	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
Secondary	CRP	C-Reactive Protein in mg/L	Up to follow-up day 14 after study start
Secondary	Serum chemistry + complete blood cell (CBC) with differential	Will be summarized descriptively.	Up to follow-up day 14 after study start
Secondary	Blood gases pH(when available)	pH (no unit)	Up to follow-up day 14 after study start
Secondary	Albumin	Albumin in gm/dL	Up to follow-up day 14 after study start
Secondary	Procalcitonin	Procalcitonin in ng/mL	Up to follow-up day 14 after study start
Secondary	Aspartate aminotransferase (AST)	Asparatate Aminotransferase in units/L	Up to follow-up day 14 after study start
Secondary	Creatine kinase	Creatinine in mg/dL	Up to follow-up day 14 after study start
Secondary	Prothrombin time (PT)/partial thromboplastin time (PTT)	Coagulation pathway time in seconds	Up to follow-up day 14 after study start
Secondary	Troponin	Troponin-I in ng/mL	Up to follow-up day 14 after study start
Secondary	Lactate	Lactic Acid in mmol/L	Up to follow-up day 14 after study start
Secondary	NT-pBNP (cardiac injury)	B-Natriuretic Peptid in pg/mL	Up to follow-up day 14 after study start
Secondary	Gamma-glutamyl transferase (GGT)	Gamma-glutamyl transferase in units/L	Up to follow-up day 14 after study start
Secondary	Triglycerides	Trygliciericdes in mg/dL	Up to follow-up day 14 after study start
Secondary	Fibrinogen	Fibrinogen in mg/dL	Up to follow-up day 14 after study start
Secondary	Changes in CD8 T cells	Will be summarized descriptively.	Up to follow-up day 14 after study start
Secondary	Changes in CD4 T cells	Will be summarized descriptively.	Up to follow-up day 14 after study start
Secondary	Changes in serum antibodies against COVID-19 epitope	Will be summarized descriptively.	Up to follow-up day 14 after study start
Secondary	LDH	Lactate Dehydrogenase in units/L	Up to follow-up day 14 after study start
Secondary	D-Dimer	D-Dimer in ng/mL	Up to follow-up day 14 after study start
Secondary	IL-6	Interleukin-6 in pg/mL	Up to follow-up day 14 after study start
Secondary	Myoglobin	Myoglobin in ng/mL	Up to follow-up day 14 after study start
Secondary	Potassium	Potassium in mmol/L	Up to follow-up day 14 after study start
Secondary	Ferritin	Ferritin in ng/mL	Up to follow-up day 14 after study start
Secondary	ALT	Alanine Aminotransferase in units/L	Up to follow-up day 14 after study start

External Links

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