Cytokine Storm, Pneumonia, Viral
Conditions
Keywords
Low Dose Radiotherapy, COVID19 pneumonia, Anti-inflammatory effects, Acute Respiratory Distress Syndrome (ARDS)
Brief summary
The host response against the coronavirus 2 (SARS-CoV-2) appears to be mediated by a 'cytoquine storm' developing a systemic inflammatory mechanism and an acute respiratory distress syndrome (ARDS), in the form of a bilateral pneumonitis, requiring invasive mechanical ventilation (IMV) in an important group of patients. In terms of preventing progression to the critical phase with the consequent need of admission to the intensive care units (ICU), it has been recently proposed that this inflammatory cytoquine-mediated process can be safely treated by a single course of ultra-low radiotherapy (RT) dose \< 1 Gy. The main purpose of the study was to analyze the efficacy of ultra low-dose pulmonary RT, as an anti-inflammatory intention in patients with SARS-Cov-2 pneumonia with a poor or no response to standard medical treatment and without IMV.
Detailed description
The exceedingly high mortality rates of severe and critical COVID-19 warrant the evaluation of novel therapies that could potentially mitigate the advanced disease manifestations. In this context, is proposes a prospective multicenter study. It will include 15 patients, to assess the feasibility and efficacy of low-dose lung irradiation in COVID-19 pneumonia.
Interventions
DRUGPiperacillin/tazobactam
4 g / 0.5 g administered every 6-8 hours through a vein (directly into the bloodstream), for 5-14 days. Adjustment to kidney function
DRUGLow molecular weight heparin
prophylactic doses
DRUGCorticosteroid injection
250mg x 3 boluses
DRUGTocilizumab
600mg single dose
RADIATIONUltra-Low-dose radiotherapy
The total dose to be administered was 0.8 Gy in an only single session including both whole-lungs extended 1cm isometric in all directions.
DEVICEventilatory support with oxygen therapy
Oxygen Therapy: Nasal Cannula (NC); Ventimask (VMK) or VMK with reservoir
DRUGLopinavir/ritonavir
100/400 mg/12h; 7-10 days
DRUGHydroxychloroquine
200 mg/12h
DRUGAzithromycin
500 mg/24h, 3 days
Sponsors
Hospital La Milagrosa
Hospital Vithas Valencia Consuelo
Fundacion GenesisCare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
an experimental group will receive ultra low-dose lung radiotherapy
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
1. Age \> 18 years-old. 2. Diagnosis of pneumonia due to COVID-19 serologically proven by polymerase chain reaction (PCR) or highly suspected to be COVID-related. 3. Charlson Comorbidity Index (CCI) less than 6 score. 4. Poor or no response to standard medical treatment, based on: \*% Sat02 \<93% * Oxygen therapy escalation (Understanding from less to more need for support: Nasal Cannula-NC-; Ventimask -VMK- and VMK with reservoir) * Pa02 / Fi02 (blood gas analysis) \<300 mmHg * 1 or more inflammatory and immunological analytical parameters such as lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen with values above the normal range, except lymphocytes. * Radiological impairment defined as worsening of TSS throughout admission or score at admission: TSS\> 5 by a diagnostic baseline CT scan. 5. Eastern Cooperative Oncology Group (ECOG) Status \< or = 3 6. Life expectancy (LE)\> 1 month at hospital admission for COVID-19 7. No previous thoracic RT (relative-individualization criteria) or chemotherapy (chemoinduced pulmonary toxicity, eg Bleomycin). 8. Verbal information on the procedure, objective and secondary effects, acceptance and signing of informed consent by the patient or legal guardian.
Exclusion criteria
* Failure to meet the inclusion criteria. * Any uncontrolled intercurrent illness that would put the patient at greater risk or limit compliance with study requirements in the opinion of the investigator. * Patients admitted in ICU. * Refusal of treatment after verbal information.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oxygen Therapy Status at Day 2 | At 2 after RT | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir \>VMK \>Nasal Cannula-(NC).) |
| Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2 | At 2 days after RT | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy \>93% (Pulse oximeter measurement) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Test at Day 2 | At 2 days after RT | Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen) |
| Oxygen Therapy Status at Day 5 | At 5 after RT | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir \>VMK \>Nasal Cannula-(NC).) |
| Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5 | At 5 days after RT | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy \>93% (Pulse oximeter measurement) |
| Blood Test at Day 5 | At 5 days after RT | Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen) |
| Oxygen Therapy Status at Day 7 | At 7 after RT | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir \>VMK \>Nasal Cannula-(NC).) |
| Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7 | At 7 days after RT | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy \>93% (Pulse oximeter measurement) |
| Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7 | At 7 days after RT | To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in \> or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points) |
| Recovery time | From RT administration until hospital discharge or death | Recovery time after RT administration until hospital discharge or death (\<48h; 2-7 days; \>7 days; clinical worsening or death) |
| COVID-19 status | At 7 days after RT | COVID-19 negativization test |
| Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1 | At 1 month after RT | To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in \> or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points) |
| Acute Toxicity | 1-3 months after RT | Toxicity was assessed and rated according to the NIH Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and RTOG scales. |
| Blood Test at Day 7 | At 7 days after RT | Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen) |
| Blood Gas Analysis at Day 2 | At 2 days after RT | Pa02 / Fi02 \> 300 mmHg |
Countries
Spain
Outcome results
None listed