Low Dose Radiotherapy in COVID-19 Pneumonia

Assessment of Adding Low Dose Pulmonary Radiotherapy to the National Protocol of COVID-19 Management: A Pilot Trial

Moderate to severe cases of SARS-associated ARDS based on inclusion/ exclusion criteria and the decision made in multi- disciplinary team are treated with 0.5 Gy whole lung radiation.

Study Overview

• Status: Unknown
• Conditions: COVID; SARS (Severe Acute Respiratory Syndrome)
• Intervention / Treatment: Radiation: Low Dose Radiotherapy

Detailed Description

SARS-associated ARDS (acute respiratory distress syndrome) is the most fatal outcome of COVID-19 systemic infection. To overcome the uncontrolled inflammation leading to ARDS and respiratory failure, several drugs have been investigated in this situation with the most promising results coming from anti-inflammatory agents that directly or indirectly inhibit IL-6 and its counterparts of inflammation.

Low dose radiation, as opposed to high dose, has documented anti-inflammatory effects that are exercised through various mechanisms including decrease in pro-inflammatory cytokines such as IL-6.

In this pilot clinical trial, the patients are carefully selected according to inclusion /exclusion criteria and the clinical judgement of the multi- disciplinary team.Their diagnostic CT scan will be used to plan an AP/ PA radiotherapy treatment to both lungs and the set-up positioning information is obtained from anatomical landmarks. The patient will be referred for a fraction of 0.5 Gy to both lungs and for the next 28 days the clinical para-clinical and radiologic variables of disease severity will be monitored closely. Should the patient's clinical course indicate and the multi- disciplinary team approves, they may be subjected to another fraction of 0.5 Gy to a maximum of 1 Gy in two fractions at least 72 hours apart. All the patients will also receive the standard national protocol of COVID-19 management.

A total of 5 patients will be enrolled in the RT arm, providing favourable results seen in the first set of patients, the team will decide on recruiting a larger number for a phase II clinical trial.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Imam Hossein Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed COVID-19 diagnosis ( PCR or serologic or radiographic)
• Presence of pulmonary involvement ( defined by P/F ratio or NIV need)
• Less than 3 days since the onset of ARDS
• Age > 60 years
• ↑ IL-6 ( if available)
• ↑ CRP

Exclusion Criteria:

• Lack of informed consent
• Inability to transfer to the radiation unit
• Hemodynamic instability
• Septic shock and organ dysfunction
• Severe ARDS P/F ratio ≤ 100 mmHg
• History of cardiac failure
• Contraindications to radiation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• 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: Low Dose Radiotherapy; 0.5 Gy radiation to both lungs in an AP/PA fashion	Radiation: Low Dose Radiotherapy; 0.5 Gy radiation to both lungs in an AP/PA treatment plan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline blood oxygenation	O2 saturation	28 days
Number of Hospital stay days	Total days the patient is admitted to hospital	28 days
Number of ICU stay days	Total days the patient is admitted to ICU	28 days
Number of intubation events	Total number of intubations performed after the treatment	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WBC	Changes in WBC count if base-line is abnormal	28 days
Platelets	Changes in Platelets count if base-line is abnormal	28 days
CRP	Changes in CRP serum level	Day 1
CRP	Changes in CRP serum level	Day 2
CRP	Changes in CRP serum level	Day 3
CRP	Changes in CRP serum level	Day 4
CRP	Changes in CRP serum level	Day 5
IL-6	Changes in IL-6 serum level	Day 1
IL-6	Changes in IL-6 serum level	Day 2
IL-6	Changes in IL-6 serum level	Day 3
IL-6	Changes in IL-6 serum level	Day 4
IL-6	Changes in IL-6 serum level	Day 5

Collaborators and Investigators

• Sponsor: Shahid Beheshti University of Medical Sciences
• Investigators: Study Chair: Ahmad Ameri, Prof., Shahid Beheshti University of Medical Sciences; Principal Investigator: Nazanin Rahnama, M.D., Shahid Beheshti University of Medical Sciences

Publications and helpful links

General Publications

• Kirkby C, Mackenzie M. Is low dose radiation therapy a potential treatment for COVID-19 pneumonia? Radiother Oncol. 2020 Jun;147:221. doi: 10.1016/j.radonc.2020.04.004. Epub 2020 Apr 6. No abstract available.
• Calabrese EJ, Dhawan G. How radiotherapy was historically used to treat pneumonia: could it be useful today? Yale J Biol Med. 2013 Dec 13;86(4):555-70.
• Large M, Hehlgans S, Reichert S, Gaipl US, Fournier C, Rodel C, Weiss C, Rodel F. Study of the anti-inflammatory effects of low-dose radiation: The contribution of biphasic regulation of the antioxidative system in endothelial cells. Strahlenther Onkol. 2015 Sep;191(9):742-9. doi: 10.1007/s00066-015-0848-9. Epub 2015 Jun 8.
• Clayton B. Hess, MD, MPH, and Mohammad K. Khan, MD, PhD, "Low dose chest radiation for COVID-19 patients" Winship Emory News post, April 27, 2020
• Kefayat A, Ghahremani F. Low dose radiation therapy for COVID-19 pneumonia: A double-edged sword. Radiother Oncol. 2020 Jun;147:224-225. doi: 10.1016/j.radonc.2020.04.026. Epub 2020 Apr 20. No abstract available.
• Stefano M Magrini, Prof et al. COVID-19 Pneumonitis Low Dose Lung Radiotherapy (COLOR-19). ClinicalTrials.gov Identifier: NCT04377477

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2020
• Primary Completion (Actual): August 30, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: May 13, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 15, 2020

Study Record Updates

• Last Update Posted (Actual): November 10, 2020
• Last Update Submitted That Met QC Criteria: November 6, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: COVID-19; anti-inflammatory; Low Dose Lung 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; Severe Acute Respiratory Syndrome; COVID-19
• Other Study ID Numbers: 23568; IRCT20200509047366N1 (Registry Identifier: Iranian Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared after the completion of study to other researchers.
• IPD Sharing Time Frame: After the completion of trial for one year.
• IPD Sharing Access Criteria: Verified researchers
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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