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

NCT ID: NCT04394182

Last Updated: 2022-03-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

NA

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-21

Study Completion Date

2022-03-21

Brief Summary

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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

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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.

Conditions

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Pneumonia, Viral Cytokine Storm

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

an experimental group will receive ultra low-dose lung radiotherapy
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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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)

Group Type EXPERIMENTAL

Ultra-Low-dose radiotherapy

Intervention Type RADIATION

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.

ventilatory support with oxygen therapy

Intervention Type DEVICE

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

Lopinavir/ritonavir

Intervention Type DRUG

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

Hydroxychloroquine

Intervention Type DRUG

200 mg/12h

Azithromycin

Intervention Type DRUG

500 mg/24h, 3 days

Piperacillin/tazobactam

Intervention Type DRUG

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

Low molecular weight heparin

Intervention Type DRUG

prophylactic doses

Corticosteroid injection

Intervention Type DRUG

250mg x 3 boluses

Tocilizumab

Intervention Type DRUG

600mg single dose

Interventions

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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.

Intervention Type RADIATION

ventilatory support with oxygen therapy

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

Intervention Type DEVICE

Lopinavir/ritonavir

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

Intervention Type DRUG

Hydroxychloroquine

200 mg/12h

Intervention Type DRUG

Azithromycin

500 mg/24h, 3 days

Intervention Type 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

Intervention Type DRUG

Low molecular weight heparin

prophylactic doses

Intervention Type DRUG

Corticosteroid injection

250mg x 3 boluses

Intervention Type DRUG

Tocilizumab

600mg single dose

Intervention Type DRUG

Other Intervention Names

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Kaletra Dolquine Urbason

Eligibility Criteria

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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.

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital La Milagrosa

UNKNOWN

Sponsor Role collaborator

Hospital Vithas Valencia Consuelo

UNKNOWN

Sponsor Role collaborator

Fundacion GenesisCare

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Escarlata López Ramírez, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fundacion GenesisCare

Locations

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Hospital La Milagrosa, GenesisCare

Madrid, , Spain

Site Status

Hospital Vithas Valencia Consuelo

Valencia, , Spain

Site Status

Countries

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Spain

References

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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.

Reference Type RESULT
PMID: 32342871 (View on PubMed)

Berk LB, Hodes PJ. Roentgen therapy for infections: an historical review. Yale J Biol Med. 1991 Mar-Apr;64(2):155-65.

Reference Type RESULT
PMID: 1750226 (View on PubMed)

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.

Reference Type RESULT
PMID: 24348219 (View on PubMed)

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.

Reference Type RESULT
PMID: 31933547 (View on PubMed)

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.

Reference Type RESULT
PMID: 22907572 (View on PubMed)

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.

Reference Type RESULT
PMID: 31060383 (View on PubMed)

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.

Reference Type RESULT
PMID: 17487675 (View on PubMed)

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.

Reference Type RESULT
PMID: 16368644 (View on PubMed)

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.

Reference Type RESULT
PMID: 32140081 (View on PubMed)

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.

Reference Type RESULT
PMID: 32373721 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33502567 (View on PubMed)

Related Links

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https://doi.org/10.1007/s00330-020-06817-6

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

Other Identifiers

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20.4.1597-GHM

Identifier Type: -

Identifier Source: org_study_id

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