Clinical trial NCT04331470: Evaluation of Efficacy of Levamisole and Formoterol+Budesonide in Treatment of COVID-19
Official title: Evaluation of Efficacy of Pharmacotherapy Treatment of COVID- 19 Infection Using Oral Levamisole and Formoterol+Budesonide Inhaler and Comparison of This Treatment Protocol With Standard National Treatment of the Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: COVID-19
Lead sponsor: Fasa University of Medical Sciences
Sponsor class: OTHER
First posted: 2020-04-02
Enrollment: 30
Sex: ALL
Minimum age (years): 15
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study is two armed , double blind, parallel, randomized clinical trial.
Primary purpose: TREATMENT

Brief summary: New Corona virus (COVID-19) has made a horrible situation for all of the countries. This disease is not only a health problem but also economy, culture and the whole entity of the countries is under attack by the virus. This disease seems to affect the body in two different pathology pathways. From one side virus can decrease activity of immune system in the blood stream and whole body and from other side it can attack the respiratory cells. Tissue biopsy shows that immune cells penetrate into the Lung tissue and we have accumulation and over activity of Immune cells in the lung. This inflammation in respiratory tract probably is the major cause of Cytokine storm and release of TNF-α and IL-6 into the blood.

It seems that by three strategy disease can be treated. 1- By using systemic immune simulators. 2- By using topical anti-inflammatory drug in the respiratory system (Steroids or NSAIDs) 3- By inhibition of replication of the virus in the attacked cells.

Detailed description: Looking at the pathology of this disease shows that COVID-19 virus binds to the Angiotensin converting enzyme II (ACE II) which is located on the surface of different cells in the body and specially on the cells of respiratory system. This enzyme is responsible to turn angiotensin II into angiotensin1-7. It is also turns angiotensin I into angiotensin 1-9.

When ACEII would be blocked by virus level of angiotensin II will be increased and this enzyme along with vasoconstriction, makes cells to manufacture TNF α and IL-6 which are responsible for cytokine storm and Lymphopenia. Also presence of virus and virus shell on the surface of the infected cells make immune system to attack to the respiratory system hence effect of angiotensin II inside the cell causes fibrosis of the respiratory cells. This inflammation and tissue damage make Acute Respiratory Distress syndrome (ARDS) which is lethal for patients. There is a dilemma in treatment of this infection. From one side it doesn't make sense to decrease the immune response hence it will make the infection worse. And from other side stimulation of the immune response because of respiratory inflammation can expedite process of lethal ARDS. A new strategy for treatment of this disease which consists of local anti- inflammatory and systemic immune stimulant drugs can be considered as a reasonable strategy.As immunostimulator, Levamisole can increase Lymphocytes and empower the immunity of the body. This drug can also bind to Papaine Like Protease(PL-pro) of the shell of the virus which is necessary for virulence of COVID-19. It also can decrease level of TNF α and IL-6, and as a chemical adjutant can introduce the virus to the immune system. In addition to Levamisole, Formoterol+Budesonide inhaler can be used in this protocol. Budesonide is a steroid and can suppress the immune reaction locally in the respiratory system. Formoterol is β2 agonist and can open airways. It also can bind to PL-pro and can neutralize the virus according to the published articles.

Eligibility criteria: Inclusion Criteria:

Definitely positive COVID-19 patients

Exclusion Criteria:

Patients with acute respiratory problems including patients with:

1. Spo2\<60%
2. Severe respiratory distress
3. Heamodynamic instabilitty
4. Acid base disturbance
5. Severe Anemia Patients with severe hepatic diseases Patients with Nurvous system diseases

Primary outcomes:
measure: Clear chest CT-scan
timeFrame: between 3-7 days
measure: PCR test
timeFrame: between 3-7 days
Secondary outcomes:
measure: Physical statues of patient
timeFrame: Between 3-7 days
Other outcomes:
Locations:
city: Fasa
country: Iran, Islamic Republic of
facility: Vali-Asr Hospital
state: Fars
Study officials:
affiliation: Fasa University of Medical Sciences
name: Siamack Afazeli
role: PRINCIPAL_INVESTIGATOR
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