Low Dose Anti-inflammatory Radiotherapy for the Treatment of Pneumonia by COVID-19

Study Overview
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Brief Summary
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Low radiation doses produce anti-inflammatory effects, which may be useful in the treatment of respiratory complications of COVID-19. This type of treatment is non-invasive and therefore, a priori, it can be used in all types of patients. Main objective: To evaluate the efficacy of low-dose lung irradiation as an adjunctive treatment in interstitial pneumonia in patients with COVID-19 by improving the PAFI O2 by 20% measured 48h after treatment with respect to the pre baseline measurement. -irradiation.

Detailed Description
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Study design: This is a prospective multicenter study in 2 phases: Exploratory phase. It will include 10 patients, to assess the feasibility and efficacy of low-dose lung irradiation. If a minimum efficiency of 30% is not achieved, the study will not be continued. Comparative phase in two groups, a control group, which will only receive pharmacological treatment, and an experimental one. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm, which will receive low-dose lung irradiation.

Official Title
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Low Dose Anti-inflammatory Radiotherapy for the Treatment of Pneumonia by COVID-19: Multi-central Prospective Study

Conditions
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Pneumonia, Viral

Intervention / Treatment
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* Radiation: Low-dose radiotherapy
* Drug: Hydroxychloroquine Sulfate
* Drug: Ritonavir/lopinavir
* Drug: Tocilizumab Injection [Actemra]
* Drug: Azithromycin
* Drug: Corticosteroid
* Drug: Low molecular weight heparin
* Device: Oxygen supply


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >=18 years old Moderate to severe COVID-19 pneumonia with fewer than 8 days of symptom onset and currently receiving standard medication for COVID-19 at appropriate doses PAFIO2 of less than 300 mmHg or SaFI02 <315 mmHg Patients who are not candidates for admission to the Intensive Care Unit due to age, concomitant diseases or general condition. One of the following conditions: or IL6 greater than 40 or PCR> 100mg / l D-dimer greater than 1500ng / ml Suspected cytokine release syndrome Have read the information sheet and signed the informed consent Exclusion Criteria: Age <18 years Failure to meet the inclusion criteria Leukopenia <1000 Pregnancy Not understanding or refusing the purpose of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>a control group only receive pharmacological treatment | Drug: Hydroxychloroquine Sulfate<br>* 200 mg/12h for 5 days<br>* Other names: Dolquine;Drug: Ritonavir/lopinavir<br>* 400/100 mg/12h for 7-10 days<br>* Other names: Kaletra;Drug: Tocilizumab Injection [Actemra]<br>* 600 mg/day for 1-2 doses<br>* Other names: Actemra;Drug: Azithromycin<br>* 500 mg/24h for 3 days<br>Drug: Corticosteroid<br>* Corticosteroids (methylprednisolone/dexamethasone/prednisone)<br>Drug: Low molecular weight heparin<br>* low molecular weight heparin (LMWH) in prophylaxis of venous thromboembolism<br>Device: Oxygen supply<br>* Oxygen<br>|
| Experimental: Experimental group<br>an experimental group will receive low-dose lung irradiation | Radiation: Low-dose radiotherapy<br>* Bilateral low-dose lung irradiation: 0.5 Gy in a single fraction. Optionally, additional 0.5 Gy fraction 48h later<br>Drug: Hydroxychloroquine Sulfate<br>* 200 mg/12h for 5 days<br>* Other names: Dolquine;Drug: Ritonavir/lopinavir<br>* 400/100 mg/12h for 7-10 days<br>* Other names: Kaletra;Drug: Tocilizumab Injection [Actemra]<br>* 600 mg/day for 1-2 doses<br>* Other names: Actemra;Drug: Azithromycin<br>* 500 mg/24h for 3 days<br>Drug: Corticosteroid<br>* Corticosteroids (methylprednisolone/dexamethasone/prednisone)<br>Drug: Low molecular weight heparin<br>* low molecular weight heparin (LMWH) in prophylaxis of venous thromboembolism<br>Device: Oxygen supply<br>* Oxygen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of low-dose pulmonary irradiation assessed by change in PAFI O2 by 20% | To evaluate the efficacy of low-dose pulmonary irradiation as an adjunctive treatment in interstitial pneumonia in patients with COVID-19 by improving the PAFI O2 by 20% measured 48h after treatment with respect to baseline pre-irradiation measurement. . In cases of impossibility the SaFiO2 will be determined | Day 2 after interventional radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Lung toxicity measured according to CTCAEv5 | Day 30 and day 90 after interventional radiotherapy | 
| Change of the radiological image | Chest CT | Days 7 and day 30 after interventional radiotherapy | 
| Overall mortality | Death of any cause | Day 15 and Day 30 after interventional radiotherapy | 
| Measure of pro-inflammatory interleukins | Interleukins IL-6, IL-10, IL-1, IL-2, IL-8 (pg/ml) | Days 1, day 4 and day 7 after interventional radiotherapy | 
| Measure of trasforming growth factor (TGF-b) | TGF-β (ng/ml) | Days 1, day 4 and day 7 after interventional radiotherapy | 
| Measure of tumor necrosis factor alpha (TNF-a) | TNF-α (pg/ml) | Days 1, day 4 and day 7 after interventional radiotherapy | 
| Determining overexpression of pro-inflammatory selectin | Overexpression of L-, E-, and P-selectin | Days 1, day 4 and day 7 after interventional radiotherapy | 
| Determining cell adhesion molecules (CAMs) | Overexpression of ICAM-1, VCAM | Days 1, day 4 and day 7 after interventional radiotherapy | 
| Measure of marker of oxidative stress PON-1 | PON-1(paraoxonase and arylesterase activity) (IU/ml) | Days 1, day 4 and day 7 after interventional radiotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RADIATION, COVID 19, Anti-inflammatory effects