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

NCT04394182 | Suspended

• 1 other identifier: 20.4.1597-GHM
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

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.

Conditions

Pneumonia, Viral; Cytokine Storm

Keywords

Low Dose Radiotherapy; COVID19 pneumonia; Anti-inflammatory effects; Acute Respiratory Distress Syndrome (ARDS)

Outcome Measures

Primary Outcomes (2)

• 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).)

  At 2 after RT

• 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)

  At 2 days after RT

Secondary Outcomes (13)

• Blood Gas Analysis at Day 2

  At 2 days after RT

• Blood Test at Day 2

  At 2 days after RT

• Oxygen Therapy Status at Day 5

  At 5 after RT

• Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5

  At 5 days after RT

• Blood Test at Day 5

  At 5 days after RT

Study Arms (1)

An experimental group receiving radiotherapy

EXPERIMENTAL

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; 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

Interventions

Ultra-Low-dose radiotherapy 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.

An experimental group receiving radiotherapy

ventilatory support with oxygen therapy DEVICE

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

An experimental group receiving radiotherapy

Lopinavir/ritonavir DRUG

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

Also known as: Kaletra

An experimental group receiving radiotherapy

Hydroxychloroquine DRUG

200 mg/12h

Also known as: Dolquine

An experimental group receiving radiotherapy

Azithromycin DRUG

500 mg/24h, 3 days

An experimental group receiving radiotherapy

Piperacillin/tazobactam 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

An experimental group receiving radiotherapy

Low molecular weight heparin DRUG

prophylactic doses

An experimental group receiving radiotherapy

Corticosteroid injection DRUG

250mg x 3 boluses

Also known as: Urbason

An experimental group receiving radiotherapy

Tocilizumab DRUG

600mg single dose

An experimental group receiving radiotherapy

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundacion GenesisCare: lead
• Hospital La Milagrosa: collaborator
• Hospital Vithas Valencia Consuelo: collaborator

Study Sites (2)

Hospital La Milagrosa, GenesisCare

Madrid, 28010, Spain

Location

Hospital Vithas Valencia Consuelo

Valencia, 46007, Spain

Location

Related Publications (11)

• 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.

  PMID: 32342871 RESULT

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

  PMID: 1750226 RESULT

• 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.

  PMID: 24348219 RESULT

• 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.

  PMID: 31933547 RESULT

• 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.

  PMID: 22907572 RESULT

• 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.

  PMID: 31060383 RESULT

• 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.

  PMID: 17487675 RESULT

• 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.

  PMID: 16368644 RESULT

• 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.

  PMID: 32140081 RESULT

• 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.

  PMID: 32373721 RESULT

• 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.

  PMID: 33502567 DERIVED

Related Links

• 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

MeSH Terms

Conditions

Pneumonia, Viral; Cytokine Release Syndrome; Respiratory Distress Syndrome

Interventions

Oxygen Inhalation Therapy; Lopinavir; lopinavir-ritonavir drug combination; Hydroxychloroquine; Azithromycin; Piperacillin, Tazobactam Drug Combination; Heparin, Low-Molecular-Weight; Adrenal Cortex Hormones; Methylprednisolone; tocilizumab

Condition Hierarchy (Ancestors)

Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Respiration Disorders

Intervention Hierarchy (Ancestors)

Respiratory Therapy; Therapeutics; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Tazobactam; Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Piperacillin; Ampicillin; Penicillin G; Sulfur Compounds; Sulfones; Drug Combinations; Pharmaceutical Preparations; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Escarlata López Ramírez, MD, PhD

  Fundacion GenesisCare

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: an experimental group will receive ultra low-dose lung radiotherapy

Study Record Dates

• First Submitted: May 15, 2020
• First Posted: May 19, 2020
• Study Start: April 21, 2020
• Primary Completion: December 31, 2020
• Study Completion: March 21, 2022
• Last Updated: March 29, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

ES (2)