Back to resultsUltra Low Doses of Therapy With Radiation Applicated to COVID-19 (ULTRA-COVID)
Primary Purpose
Pneumonia, Viral, Cytokine Storm
Status
Suspended
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Ultra-Low-dose radiotherapy
ventilatory support with oxygen therapy
Lopinavir/ritonavir
Hydroxychloroquine
Azithromycin
Piperacillin/tazobactam
Low molecular weight heparin
Corticosteroid injection
Tocilizumab
Sponsored by
About this trial
This is an interventional supportive care trial for Pneumonia, Viral focused on measuring Low Dose Radiotherapy, COVID19 pneumonia, Anti-inflammatory effects, Acute Respiratory Distress Syndrome (ARDS)
Eligibility Criteria
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.
Sites / Locations
- Hospital La Milagrosa, GenesisCare
- Hospital Vithas Valencia Consuelo
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
An experimental group receiving radiotherapy
Arm Description
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)
Outcomes
Primary Outcome Measures
Oxygen Therapy Status at Day 2
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
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
Pa02 / Fi02 > 300 mmHg
Blood Test at Day 2
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
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
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
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
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
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
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
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
Recovery time after RT administration until hospital discharge or death (<48h; 2-7 days; >7 days; clinical worsening or death)
COVID-19 status
COVID-19 negativization test
Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1
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
Toxicity was assessed and rated according to the NIH Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and RTOG scales.
Full Information
NCT ID
NCT04394182
First Posted
May 15, 2020
Last Updated
March 14, 2022
Sponsor
Fundacion GenesisCare
Collaborators
Hospital La Milagrosa, Hospital Vithas Valencia Consuelo
1. Study Identification
Unique Protocol Identification Number
NCT04394182
Brief Title
Ultra Low Doses of Therapy With Radiation Applicated to COVID-19
Acronym
ULTRA-COVID
Official Title
Low Doses of Lung Radiation Therapy in Cases of COVID-19 Pneumonia: Prospective Multicentric Study in Radiation Oncology Centers
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Suspended
Why Stopped
lack of recruitment
Study Start Date
April 21, 2020 (Actual)
Primary Completion Date
December 31, 2020 (Actual)
Study Completion Date
March 21, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundacion GenesisCare
Collaborators
Hospital La Milagrosa, Hospital Vithas Valencia Consuelo
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia, Viral, Cytokine Storm
Keywords
Low Dose Radiotherapy, COVID19 pneumonia, Anti-inflammatory effects, Acute Respiratory Distress Syndrome (ARDS)
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
an experimental group will receive ultra low-dose lung radiotherapy
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
An experimental group receiving radiotherapy
Arm Type
Experimental
Arm Description
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)
Intervention Type
Radiation
Intervention Name(s)
Ultra-Low-dose radiotherapy
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
ventilatory support with oxygen therapy
Intervention Description
Oxygen Therapy: Nasal Cannula (NC); Ventimask (VMK) or VMK with reservoir
Intervention Type
Drug
Intervention Name(s)
Lopinavir/ritonavir
Other Intervention Name(s)
Kaletra
Intervention Description
100/400 mg/12h; 7-10 days
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Other Intervention Name(s)
Dolquine
Intervention Description
200 mg/12h
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Intervention Description
500 mg/24h, 3 days
Intervention Type
Drug
Intervention Name(s)
Piperacillin/tazobactam
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Low molecular weight heparin
Intervention Description
prophylactic doses
Intervention Type
Drug
Intervention Name(s)
Corticosteroid injection
Other Intervention Name(s)
Urbason
Intervention Description
250mg x 3 boluses
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Intervention Description
600mg single dose
Primary Outcome Measure Information:
Title
Oxygen Therapy Status at Day 2
Description
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).)
Time Frame
At 2 after RT
Title
Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2
Description
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)
Time Frame
At 2 days after RT
Secondary Outcome Measure Information:
Title
Blood Gas Analysis at Day 2
Description
Pa02 / Fi02 > 300 mmHg
Time Frame
At 2 days after RT
Title
Blood Test at Day 2
Description
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)
Time Frame
At 2 days after RT
Title
Oxygen Therapy Status at Day 5
Description
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).)
Time Frame
At 5 after RT
Title
Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5
Description
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)
Time Frame
At 5 days after RT
Title
Blood Test at Day 5
Description
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)
Time Frame
At 5 days after RT
Title
Oxygen Therapy Status at Day 7
Description
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).)
Time Frame
At 7 after RT
Title
Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7
Description
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)
Time Frame
At 7 days after RT
Title
Blood Test at Day 7
Description
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)
Time Frame
At 7 days after RT
Title
Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7
Description
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)
Time Frame
At 7 days after RT
Title
Recovery time
Description
Recovery time after RT administration until hospital discharge or death (<48h; 2-7 days; >7 days; clinical worsening or death)
Time Frame
From RT administration until hospital discharge or death
Title
COVID-19 status
Description
COVID-19 negativization test
Time Frame
At 7 days after RT
Title
Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1
Description
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)
Time Frame
At 1 month after RT
Title
Acute Toxicity
Description
Toxicity was assessed and rated according to the NIH Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and RTOG scales.
Time Frame
1-3 months after RT
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Escarlata López Ramírez, MD, PhD
Organizational Affiliation
Fundacion GenesisCare
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital La Milagrosa, GenesisCare
City
Madrid
ZIP/Postal Code
28010
Country
Spain
Facility Name
Hospital Vithas Valencia Consuelo
City
Valencia
ZIP/Postal Code
46007
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Medical history and biographical and clinical data of each patient will be recorded and shared.
The overall results of any research conducted will be available on study data publication.
Citations:
PubMed Identifier
32342871
Citation
Kirkby C, Mackenzie M. Is low dose radiation therapy a potential treatment for COVID-19 pneumonia? Radiother Oncol. 2020 Jun;147:221. doi: 10.1016/j.radonc.2020.04.004. Epub 2020 Apr 6. No abstract available.
Results Reference
result
PubMed Identifier
1750226
Citation
Berk LB, Hodes PJ. Roentgen therapy for infections: an historical review. Yale J Biol Med. 1991 Mar-Apr;64(2):155-65.
Results Reference
result
PubMed Identifier
24348219
Citation
Calabrese EJ, Dhawan G. How radiotherapy was historically used to treat pneumonia: could it be useful today? Yale J Biol Med. 2013 Dec 13;86(4):555-70.
Results Reference
result
PubMed Identifier
31933547
Citation
Cuttler JM. Application of Low Doses of Ionizing Radiation in Medical Therapies. Dose Response. 2020 Jan 6;18(1):1559325819895739. doi: 10.1177/1559325819895739. eCollection 2020 Jan-Mar.
Results Reference
result
PubMed Identifier
22907572
Citation
Arenas M, Sabater S, Hernandez V, Rovirosa A, Lara PC, Biete A, Panes J. Anti-inflammatory effects of low-dose radiotherapy. Indications, dose, and radiobiological mechanisms involved. Strahlenther Onkol. 2012 Nov;188(11):975-81. doi: 10.1007/s00066-012-0170-8. Epub 2012 Aug 22.
Results Reference
result
PubMed Identifier
31060383
Citation
Calabrese EJ, Dhawan G, Kapoor R, Kozumbo WJ. Radiotherapy treatment of human inflammatory diseases and conditions: Optimal dose. Hum Exp Toxicol. 2019 Aug;38(8):888-898. doi: 10.1177/0960327119846925. Epub 2019 May 6.
Results Reference
result
PubMed Identifier
17487675
Citation
Rodel F, Keilholz L, Herrmann M, Sauer R, Hildebrandt G. Radiobiological mechanisms in inflammatory diseases of low-dose radiation therapy. Int J Radiat Biol. 2007 Jun;83(6):357-66. doi: 10.1080/09553000701317358.
Results Reference
result
PubMed Identifier
16368644
Citation
Schaue D, Jahns J, Hildebrandt G, Trott KR. Radiation treatment of acute inflammation in mice. Int J Radiat Biol. 2005 Sep;81(9):657-67. doi: 10.1080/09553000500385556.
Results Reference
result
PubMed Identifier
32140081
Citation
Torres Royo L, Antelo Redondo G, Arquez Pianetta M, Arenas Prat M. Low-Dose radiation therapy for benign pathologies. Rep Pract Oncol Radiother. 2020 Mar-Apr;25(2):250-254. doi: 10.1016/j.rpor.2020.02.004. Epub 2020 Feb 22.
Results Reference
result
PubMed Identifier
32373721
Citation
Lara PC, Burgos J, Macias D. Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment. Clin Transl Radiat Oncol. 2020 Apr 25;23:27-29. doi: 10.1016/j.ctro.2020.04.006. eCollection 2020 Jul.
Results Reference
result
PubMed Identifier
33502567
Citation
Moreno-Olmedo E, Suarez-Gironzini V, Perez M, Filigheddu T, Minguez C, Sanjuan-Sanjuan A, Gonzalez JA, Rivas D, Gorospe L, Larrea L, Lopez E. COVID-19 pneumonia treated with ultra-low doses of radiotherapy (ULTRA-COVID study): a single institution report of two cases. Strahlenther Onkol. 2021 May;197(5):429-437. doi: 10.1007/s00066-020-01743-4. Epub 2021 Jan 27.
Results Reference
derived
Links:
URL
https://doi.org/10.1007/s00330-020-06817-6
Description
Li, K., Fang, Y., Li, W. et al. CT image visual quantitative evaluation and clinical classification of coronavirus disease (COVID-19). Eur Radiol (2020). https://doi.org/10.1007/s00330-020-06817-6
Learn more about this trial
Ultra Low Doses of Therapy With Radiation Applicated to COVID-19
We'll reach out to this number within 24 hrs