Inhalation Low Dose Radionuclide Therapy in Treatment COVID-19

Conditions

Covid19, Pneumonia, Viral

Keywords

COVID-19, viral pneumonia, radionuclide therapy

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.

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Interventions

RADIATION99mTc-pertechnetate aerosol

99mTc-pertechnetate is 99mTc-labeled carbon ultrafine aerosol

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

1. Positive SARS-Cov-2 polymerase chain reaction (PCR) 2. CT confirmed pneumonia 3. Men and non-pregnant women ≥ 18 y/o with early laboratory signs of cytokine storm 4. Men and non-pregnant women \<65 y/o and/or with early laboratory signs of cytokine storm 5. Informed consent obtained for participation

Exclusion criteria

1. Age ≤ 18 2. Severe course of COVID-19 3. Pregnant or breast-feeding females 4. Severe concomitant pathology 5. Previous and/or present treatment of oncology disease (e.g. immunotherapy) 6. Autoimmune diseases, severe cardiac disease, bone marrow and/or visceral transplantation 7. Surgical treatment and/or radiotherapy of chest pathology 8. Treatment with specific antiviral and anticytokine agents a day before inhalation procedure 9. Absence of informed consent obtained for participation

Design outcomes

Primary

Measure	Time frame	Description
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.
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.
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.
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.
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.

Secondary

Measure	Time frame	Description
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.
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.

Countries

Russia

Participant flow

Participants by arm

Arm	Count
Patient With COVID-19 Pneumonia 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. 99mTc-pertechnetate aerosol: 99mTc-pertechnetate is 99mTc-labeled carbon ultrafine aerosol	11
Patient With COVID-19 Pneumonia Without Intervention Blood tests at 1, 3 and 7 days.	14
Total	25

Baseline characteristics

Characteristic	Patient With COVID-19 Pneumonia Without Intervention	Total	Patient With COVID-19 Pneumonia
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	8 Participants	12 Participants	4 Participants
Age, Categorical Between 18 and 65 years	6 Participants	13 Participants	7 Participants
Age, Continuous	59.9 Years	57.5 Years	54.3 Years
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	14 Participants	25 Participants	11 Participants
Region of Enrollment Russia	14 participants	25 participants	11 participants
Sex: Female, Male Female	5 Participants	9 Participants	4 Participants
Sex: Female, Male Male	9 Participants	16 Participants	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 11	0 / 14
other Total, other adverse events	0 / 11	0 / 14
serious Total, serious adverse events	0 / 11	0 / 14

Outcome results

Primary

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.

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.