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

Sponsor

Fundacion GenesisCare (Other)

Overall Status

Suspended

CT.gov ID

NCT04394182

Collaborator

Hospital La Milagrosa (Other), Hospital Vithas Valencia Consuelo (Other)

Enrollment

Locations

Arm

Anticipated Duration (Months)

7.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Viral Cytokine Storm	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	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

an experimental group will receive ultra low-dose lung radiotherapyan experimental group will receive ultra low-dose lung radiotherapy

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

Low Doses of Lung Radiation Therapy in Cases of COVID-19 Pneumonia: Prospective Multicentric Study in Radiation Oncology Centers

Actual Study Start Date :

Apr 21, 2020

Actual Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Mar 21, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: An experimental group receiving 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)	Radiation: Ultra-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. Device: ventilatory support with oxygen therapy Oxygen Therapy: Nasal Cannula (NC); Ventimask (VMK) or VMK with reservoir Drug: Lopinavir/ritonavir 100/400 mg/12h; 7-10 days Other Names: Kaletra Drug: Hydroxychloroquine 200 mg/12h Other Names: Dolquine Drug: Azithromycin 500 mg/24h, 3 days Drug: Piperacillin/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 Drug: Low molecular weight heparin prophylactic doses Drug: Corticosteroid injection 250mg x 3 boluses Other Names: Urbason Drug: Tocilizumab 600mg single dose

Arm

Intervention/Treatment

Experimental: An experimental group receiving 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)

Radiation: Ultra-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.

Device: ventilatory support with oxygen therapy

Oxygen Therapy: Nasal Cannula (NC); Ventimask (VMK) or VMK with reservoir

Drug: Lopinavir/ritonavir

100/400 mg/12h; 7-10 days

Other Names:

Kaletra

Drug: Hydroxychloroquine

200 mg/12h

Other Names:

Dolquine

Drug: Azithromycin

500 mg/24h, 3 days

Drug: Piperacillin/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

Drug: Low molecular weight heparin

prophylactic doses

Drug: Corticosteroid injection

250mg x 3 boluses

Other Names:

Urbason

Drug: Tocilizumab

600mg single dose

Outcome Measures

Primary Outcome Measures

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

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)
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)
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > 18 years-old.
Diagnosis of pneumonia due to COVID-19 serologically proven by polymerase chain reaction (PCR) or highly suspected to be COVID-related.
Charlson Comorbidity Index (CCI) less than 6 score.
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.

Eastern Cooperative Oncology Group (ECOG) Status < or = 3
Life expectancy (LE)> 1 month at hospital admission for COVID-19
No previous thoracic RT (relative-individualization criteria) or chemotherapy (chemoinduced pulmonary toxicity, eg Bleomycin).
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.