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

Phase 3

Active, not recruiting

• Conditions: Pneumonia; Severe Acute Respiratory Syndrome; Symptomatic COVID-19 Infection Laboratory-Confirmed
• Interventions: Radiation: Low Dose Radiation Therapy; Other: Best Practice

• Registration Number: NCT04433949
• Lead Sponsor: Emory University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-06-12
• Study First Submitted QC: 2020-06-15
• Study First Posted: 2020-06-16
• Study Start: 2020-06-23
• Primary Completion: 2022-10-19
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-08
• Last Update Posted: 2023-08-14
• Study Completion: 2024-05-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 14

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (LDRT)	Low Dose Radiation Therapy	Patients receive best supportive care + low dose RT (whole lung)
Arm I (physician choice)	Best Practice	Patients get best supportive care + physician choice of treatment

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Emory University Hospital/Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States