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

March 14, 2022 updated by: Fundacion GenesisCare

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

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.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain, 28010
        • Hospital La Milagrosa, GenesisCare
      • Valencia, Spain, 46007
        • Hospital Vithas Valencia Consuelo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Oxygen Therapy Status at Day 2
Time Frame: 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).)
At 2 after RT
Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2
Time Frame: 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)
At 2 days after RT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Gas Analysis at Day 2
Time Frame: At 2 days after RT
Pa02 / Fi02 > 300 mmHg
At 2 days after RT
Blood Test at Day 2
Time Frame: 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)
At 2 days after RT
Oxygen Therapy Status at Day 5
Time Frame: 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).)
At 5 after RT
Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5
Time Frame: 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)
At 5 days after RT
Blood Test at Day 5
Time Frame: 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)
At 5 days after RT
Oxygen Therapy Status at Day 7
Time Frame: 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).)
At 7 after RT
Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7
Time Frame: 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)
At 7 days after RT
Blood Test at Day 7
Time Frame: 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)
At 7 days after RT
Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7
Time Frame: 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)
At 7 days after RT
Recovery time
Time Frame: 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)
From RT administration until hospital discharge or death
COVID-19 status
Time Frame: At 7 days after RT
COVID-19 negativization test
At 7 days after RT
Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1
Time Frame: 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)
At 1 month after RT
Acute Toxicity
Time Frame: 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.
1-3 months after RT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundacion GenesisCare

Collaborators

Hospital La Milagrosa
Hospital Vithas Valencia Consuelo

Investigators

  • Principal Investigator: Escarlata López Ramírez, MD, PhD, Fundacion GenesisCare

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 21, 2020

Primary Completion (Actual)

December 31, 2020

Study Completion (Anticipated)

March 21, 2022

Study Registration Dates

First Submitted

May 15, 2020

First Submitted That Met QC Criteria

May 16, 2020

First Posted (Actual)

May 19, 2020

Study Record Updates

Last Update Posted (Actual)

March 29, 2022

Last Update Submitted That Met QC Criteria

March 14, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20.4.1597-GHM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Informed Consent Form (ICF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pneumonia, Viral

Clinical Trials on Ultra-Low-dose radiotherapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Saudi Arabia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe