Inhalation Low Dose Radionuclide Therapy in Treatment COVID-19

Phase 1

Completed

Conditions: Pneumonia, Viral
Covid19

Interventions: Drug: 99mTc-pertechnetate aerosol

Registration Number: NCT04724538

Lead Sponsor: National Medical Research Radiological Centre of the Ministry of Health of Russia

Brief Summary: Coronavirus disease (COVID-19) is a pandemic of unprecedented proportions with an exponential increase in incidence. Airway epithelium infection caused by coronavirus (SARS-CoV-2) triggers a cascade of difficult-to-control reactions, a so-called "cytokine storm". In contrast to the previously used method of external beam radiation therapy for patients at high risk of a cytokine storm, in present study a different dose delivery mechanism through inhalation of 99mTc-labeled carbon ultrafine aerosol obtained from a TechnegasPlus generator is used. By utilizing anthropometric phantoms the dosimetric characteristics of the applied technique and obtained the coefficients of the transition from the count rate over the area of interest to the activity contained in this area (in kBq) were studied. By observing a group of healthy volunteers after inhalation of 99mTc-labeled carbon ultrafine aerosol, the accumulated dose in the human lungs under internal irradiation of 99mTc was determined. A novel technique has been developed and the possibility of using inhaled low-dose radionuclide therapy in the complex treatment of patients with COVID-19 - associated pneumonia has been studied. As a result, a significant improvement of hematological parameters in the group of patients after inhalation of 99mTc-labeled carbon ultrafine aerosol as compared to the control group is expected.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

Inclusion Criteria

Positive SARS-Cov-2 polymerase chain reaction (PCR)
CT confirmed pneumonia
Men and non-pregnant women ≥ 18 y/o with early laboratory signs of cytokine storm
Men and non-pregnant women <65 y/o and/or with early laboratory signs of cytokine storm
Informed consent obtained for participation

Exclusion Criteria

Age ≤ 18
Severe course of COVID-19
Pregnant or breast-feeding females
Severe concomitant pathology
Previous and/or present treatment of oncology disease (e.g. immunotherapy)
Autoimmune diseases, severe cardiac disease, bone marrow and/or visceral transplantation
Surgical treatment and/or radiotherapy of chest pathology
Treatment with specific antiviral and anticytokine agents a day before inhalation procedure
Absence of informed consent obtained for participation

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy volunteers	99mTc-pertechnetate aerosol	CT-scans for exclusion of pneumonia. Accumulated absorbed dose calculation of volunteers' lungs after inhalation of 99mTc-pertechnetate aerosol from commercial gas generator which was loaded by 833 MBq of 99mTc-pertechnetate.
Patient with COVID-19 pneumonia	99mTc-pertechnetate aerosol	Inhalation of 99mTc-pertechnetate aerosol from commercial gas generator which was loaded by 4165 MBq of 99mTc-pertechnetate. CT scans a day before, 7 and 14 days after inhalation procedure. Blood tests a day before, 1, 3 and 7 days after inhalation procedure.

Primary Outcome Measures

Name	Time	Method
Absolute Neutrophil Count (ANC) After 99mTc-pertechnetate Aerosol Inhalation for Adverse Events Monitoring as Evaluation Safety of This Procedure in Patients With COVID-19 Viral Pneumonia.	Days 1, 3 and 7 after inhalation	Patients with COVID-19 viral pneumonia were observed for safety after administration of 99mTc-pertechnetate aerosol inhalation, and followed up at 1, 3, 7 days after inhalation. Patients did blood test to observe for abnormalities in clinical parameters and compare to baseline results as assessed by CTCAE v5.0. These tests were also performed in patients with COVID-19 viral pneumonia receiving standard treatment. The results were compared between the two groups.
Count of White Blood Cells (WBC) After 99mTc-pertechnetate Aerosol Inhalation for Adverse Events Monitoring as Evaluation Safety of This Procedure in Patients With COVID-19 Viral Pneumonia.	Days 1, 3 and 7 after inhalation	Patients with COVID-19 viral pneumonia were observed for safety after administration of 99mTc-pertechnetate aerosol inhalation, and followed up at 1, 3, 7 days after inhalation. Patients did blood test to observe for abnormalities in clinical parameters and compare to baseline results as assessed by CTCAE v5.0. These tests were also performed in patients with COVID-19 viral pneumonia receiving standard treatment. The results were compared between the two groups.
Absolute Lymphocyte Count (ALC) After 99mTc-pertechnetate Aerosol Inhalation for Adverse Events Monitoring as Evaluation Safety of This Procedure in Patients With COVID-19 Viral Pneumonia.	Days 1, 3 and 7 after inhalation	Patients with COVID-19 viral pneumonia were observed for safety after administration of 99mTc-pertechnetate aerosol inhalation, and followed up at 1, 3, 7 days after inhalation. Patients did blood test to observe for abnormalities in clinical parameters and compare to baseline results as assessed by CTCAE v5.0. These tests were also performed in patients with COVID-19 viral pneumonia receiving standard treatment. The results were compared between the two groups.
Level of Lactate in the Blood After 99mTc-pertechnetate Aerosol Inhalation for Adverse Events Monitoring as Evaluation Safety of This Procedure in Patients With COVID-19 Viral Pneumonia.	Days 1, 3 and 7 after inhalation	Patients with COVID-19 viral pneumonia were observed for safety after administration of 99mTc-pertechnetate aerosol inhalation, and followed up at 1, 3, 7 days after inhalation. Patients did blood test to observe for abnormalities in clinical parameters and compare to baseline results as assessed by CTCAE v5.0. These tests were also performed in patients with COVID-19 viral pneumonia receiving standard treatment. The results were compared between the two groups.
Level of D-dimer in Blood After 99mTc-pertechnetate Aerosol Inhalation for Adverse Events Monitoring as Evaluation Safety of This Procedure in Patients With COVID-19 Viral Pneumonia.	Days 1, 3 and 7 after inhalation	Patients with COVID-19 viral pneumonia were observed for safety after administration of 99mTc-pertechnetate aerosol inhalation, and followed up at 1, 3, 7 days after inhalation. Patients did blood test to observe for abnormalities in clinical parameters and compare to baseline results as assessed by CTCAE v5.0. These tests were also performed in patients with COVID-19 viral pneumonia receiving standard treatment. The results were compared between the two groups.
Count of Red Blood Cells (RBC) After 99mTc-pertechnetate Aerosol Inhalation for Adverse Events Monitoring as Evaluation Safety of This Procedure in Patients With COVID-19 Viral Pneumonia.	Days 1, 3 and 7 after inhalation	Patients with COVID-19 viral pneumonia were observed for safety after administration of 99mTc-pertechnetate aerosol inhalation, and followed up at 1, 3, 7 days after inhalation. Patients did blood test to observe for abnormalities in clinical parameters and compare to baseline results as assessed by CTCAE v5.0. These tests were also performed in patients with COVID-19 viral pneumonia receiving standard treatment. The results were compared between the two groups.
Hemoglobin Count (Hb) After 99mTc-pertechnetate Aerosol Inhalation for Adverse Events Monitoring as Evaluation Safety of This Procedure in Patients With COVID-19 Viral Pneumonia.	Days 1, 3 and 7 after inhalation	Patients with COVID-19 viral pneumonia were observed for safety after administration of 99mTc-pertechnetate aerosol inhalation, and followed up at 1, 3, 7 days after inhalation. Patients did blood test to observe for abnormalities in clinical parameters and compare to baseline results as assessed by CTCAE v5.0. These tests were also performed in patients with COVID-19 viral pneumonia receiving standard treatment. The results were compared between the two groups.
Percentage of Neutrophils (N) After 99mTc-pertechnetate Aerosol Inhalation for Adverse Events Monitoring as Evaluation Safety of This Procedure in Patients With COVID-19 Viral Pneumonia.	Days 1, 3 and 7 after inhalation	Patients with COVID-19 viral pneumonia were observed for safety after administration of 99mTc-pertechnetate aerosol inhalation, and followed up at 1, 3, 7 days after inhalation. Patients did blood test to observe for abnormalities in clinical parameters and compare to baseline results as assessed by CTCAE v5.0. These tests were also performed in patients with COVID-19 viral pneumonia receiving standard treatment. The results were compared between the two groups.

Secondary Outcome Measures

Name	Time	Method
Level of CD4+ T-cells in Blood After 99mTc-pertechnetate Aerosol Inhalation for Evaluation of Cellular Immune Response After This Procedure in Patients With COVID-19 Viral Pneumonia	Days 1, 3 and 7 after inhalation	Patients with COVID-19 viral pneumonia were observed for safety after administration of 99mTc-pertechnetate aerosol inhalation, and followed up at 1, 3, 7 days after inhalation. Patients did blood test to observe for abnormalities in clinical parameters and compare to baseline results as assessed by CTCAE v5.0. These tests were also performed in patients with COVID-19 viral pneumonia receiving standard treatment. The results were compared between the two groups.
Level of NK-cells in Blood After 99mTc-pertechnetate Aerosol Inhalation for Evaluation of Cellular Immune Response After This Procedure in Patients With COVID-19 Viral Pneumonia	Days 1, 3 and 7 after inhalation	Patients with COVID-19 viral pneumonia were observed for safety after administration of 99mTc-pertechnetate aerosol inhalation, and followed up at 1, 3, 7 days after inhalation. Patients did blood test to observe for abnormalities in clinical parameters and compare to baseline results as assessed by CTCAE v5.0. These tests were also performed in patients with COVID-19 viral pneumonia receiving standard treatment. The results were compared between the two groups.