Ultra Low Doses of Therapy With Radiation Applicated to COVID-19

Not Applicable

Suspended

• Conditions: Pneumonia, Viral; Cytokine Storm
• Interventions: Radiation: Ultra-Low-dose radiotherapy; Device: ventilatory support with oxygen therapy; Drug: Lopinavir/ritonavir; Drug: Hydroxychloroquine; Drug: Azithromycin; Drug: Piperacillin/tazobactam; Drug: Low molecular weight heparin; Drug: Corticosteroid injection; Drug: Tocilizumab

• Registration Number: NCT04394182
• Lead Sponsor: Fundacion GenesisCare

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.

Study Timeline

• Study Start: 2020-04-21
• Study First Submitted: 2020-05-15
• Study First Submitted QC: 2020-05-16
• Study First Posted: 2020-05-19
• Primary Completion: 2020-12-31
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-14
• Study Completion: 2022-03-21
• Last Update Posted: 2022-03-29

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
An experimental group receiving radiotherapy	Ultra-Low-dose radiotherapy	an experimental group with a poor or no response to standard medical treatment and without invasive mechanical ventilation (IMV) will receive ultra low-dose lung radiotherapy (0.8 Gy single dose)
An experimental group receiving radiotherapy	ventilatory support with oxygen therapy	an experimental group with a poor or no response to standard medical treatment and without invasive mechanical ventilation (IMV) will receive ultra low-dose lung radiotherapy (0.8 Gy single dose)
An experimental group receiving radiotherapy	Lopinavir/ritonavir	an experimental group with a poor or no response to standard medical treatment and without invasive mechanical ventilation (IMV) will receive ultra low-dose lung radiotherapy (0.8 Gy single dose)
An experimental group receiving radiotherapy	Piperacillin/tazobactam	an experimental group with a poor or no response to standard medical treatment and without invasive mechanical ventilation (IMV) will receive ultra low-dose lung radiotherapy (0.8 Gy single dose)
An experimental group receiving radiotherapy	Low molecular weight heparin	an experimental group with a poor or no response to standard medical treatment and without invasive mechanical ventilation (IMV) will receive ultra low-dose lung radiotherapy (0.8 Gy single dose)
An experimental group receiving radiotherapy	Corticosteroid injection	an experimental group with a poor or no response to standard medical treatment and without invasive mechanical ventilation (IMV) will receive ultra low-dose lung radiotherapy (0.8 Gy single dose)
An experimental group receiving radiotherapy	Hydroxychloroquine	an experimental group with a poor or no response to standard medical treatment and without invasive mechanical ventilation (IMV) will receive ultra low-dose lung radiotherapy (0.8 Gy single dose)
An experimental group receiving radiotherapy	Azithromycin	an experimental group with a poor or no response to standard medical treatment and without invasive mechanical ventilation (IMV) will receive ultra low-dose lung radiotherapy (0.8 Gy single dose)
An experimental group receiving radiotherapy	Tocilizumab	an experimental group with a poor or no response to standard medical treatment and without invasive mechanical ventilation (IMV) will receive ultra low-dose lung radiotherapy (0.8 Gy single dose)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Blood Gas Analysis at Day 2	At 2 days after RT	Pa02 / Fi02 \> 300 mmHg
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 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)
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)
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)
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.
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

Trial Locations

Locations (2)

Hospital La Milagrosa, GenesisCare; 🇪🇸 Madrid, Spain

Hospital Vithas Valencia Consuelo; 🇪🇸 Valencia, Spain