Clinical trial NCT04394182: Ultra Low Doses of Therapy With Radiation Applicated to COVID-19
Official title: Low Doses of Lung Radiation Therapy in Cases of COVID-19 Pneumonia: Prospective Multicentric Study in Radiation Oncology Centers
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Pneumonia, Viral
Cytokine Storm
Keywords: Low Dose Radiotherapy
COVID19 pneumonia
Anti-inflammatory effects
Acute Respiratory Distress Syndrome (ARDS)
Lead sponsor: Fundacion GenesisCare
Sponsor class: NETWORK
Collaborators: name: Hospital La Milagrosa
name: Hospital Vithas Valencia Consuelo
First posted: 2020-05-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: an experimental group will receive ultra low-dose lung radiotherapy
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Oxygen Therapy Status at Day 2
timeFrame: At 2 after RT
measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2
timeFrame: At 2 days after RT
Secondary outcomes:
measure: Blood Gas Analysis at Day 2
timeFrame: At 2 days after RT
measure: Blood Test at Day 2
timeFrame: At 2 days after RT
measure: Oxygen Therapy Status at Day 5
timeFrame: At 5 after RT
measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5
timeFrame: At 5 days after RT
measure: Blood Test at Day 5
timeFrame: At 5 days after RT
measure: Oxygen Therapy Status at Day 7
timeFrame: At 7 after RT
measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7
timeFrame: At 7 days after RT
measure: Blood Test at Day 7
timeFrame: At 7 days after RT
measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7
timeFrame: At 7 days after RT
measure: Recovery time
timeFrame: From RT administration until hospital discharge or death
measure: COVID-19 status
timeFrame: At 7 days after RT
measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1
timeFrame: At 1 month after RT
measure: Acute Toxicity
timeFrame: 1-3 months after RT
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital La Milagrosa, GenesisCare
city: Valencia
country: Spain
facility: Hospital Vithas Valencia Consuelo
Study officials:
affiliation: Fundacion GenesisCare
name: Escarlata López Ramírez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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.