Low Dose Radiotherapy in COVID-19 Pneumonia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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COVID, SARS (Severe Acute Respiratory Syndrome)

Intervention / Treatment
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* Radiation: Low Dose Radiotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose Radiotherapy<br>0.5 Gy radiation to both lungs in an AP/PA fashion | Radiation: Low Dose Radiotherapy<br>* 0.5 Gy radiation to both lungs in an AP/PA treatment plan<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Low Dose Lung Radiotherapy, anti-inflammatory