Clinical Trial to Assess Efficacy of cYclosporine Plus Standard of Care in Hospitalized Patients With COVID19

Study Overview
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Brief Summary
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The study hypothesis is that cyclosporine, added to standard treatment of hospitalized patients with COVID19 infection may improve their prognosis.

Official Title
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Open, Controlled, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Cyclosporine Plus Standard Treatment vs Standard Treatment Only in Hospitalized Patients With COVID-19 Infection

Conditions
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COVID19 Infection

Intervention / Treatment
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* Drug: Cyclosporine
* Drug: Standard treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women and men over 18 years old Clinical diagnosis of COVID19 infection (to be subsequently confirmed by PCR or specific IgM isotype Ac and with entry criteria according to the protocol of action (see Annex 2) Acceptance and signing of the consent for the study after having received the appropriate information. Exclusion criteria Known allergy or hypersensitivity to any of the medications included in the treatment arms or to any of their components. Contraindication for the use of any of the medications included (*) CsA: IR EST 4.5 (FG <30 ml / min according to the Cockcroft-Gault formula) Antimalarials (Chloroquine, hydroxychloroquine): Retinopathy, Myasthenia gravis. Lopinavir / ritonavir: severe liver failure Remdesivir, darunovir-ritonavir Doxycycline, Azithromycin Kidney failure (Stages 4 and 5: GFR <30 ml / min according to the cockcroft-Gault formula). Decompensated liver disease (Child-Pugh stages B or C) or chronic infection with virus B Pregnancy or lactation Age over 75 years Participants in another clinical trial with medication in the 28 days prior to the start of recruitment. Participation in observational studies is allowed. Refusal to participate Patient with a poor state of health or nutrition who, in the opinion of the researcher, has sufficient criteria of severity to interfere with the development of the study or its conclusions At the investigator's discretion, the patient's inability to understand or comply with the study procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A (control)<br>The control group will consist on the standard treatment that patients will receive according to hospital standard of care protocol. | Drug: Standard treatment<br>* Standard of care according to hospital protocol<br>|
| Experimental: Group B (experimental)<br>The experimental group will consist on cyclosporine added to the standard treatment that patients will receive according to hospital standard of care protocol. | Drug: Cyclosporine<br>* In the experimental group, cyclosporine will be started according to patient weight, and then increased depending on patient tolerance (monitoring renal function and blood pressure)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity Category | efficacy of the association of CsA with standard treatment in reducing the severity of COVID19 infection in hospitalized patients. | 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality Rate | efficacy of CsA in combination with standard treatment in reducing mortality | through study completion, an average of 6 weeks | 
| Number of Days in hospital | efficacy of CsA in combination with standard treatment in reducing days in hospital | through study completion, an average of 6 weeks | 
| Number of days in ICU beds | efficacy of CsA in combination with standard treatment in reducing days in ICU beds | through study completion, an average of 6 weeks | 
| Fio2 Needs | efficacy of CsA in combination with standard treatment in reducing FiO2 needs. | through study completion, an average of 6 weeks | 
| Adverse events rate | safety and tolerability of cyclosporine vs standard treatment administration | through study completion, an average of 6 weeks | 
| Change in CRP | change from baseline in C reactive protein levels | every 48 hours from randomization until patient discharge, and at the end of study visit (14 days after discharge or 14 days after end of study treatment, depending of what applies) | 
| Change in ferritin | change from baseline in ferritin levels | every 48 hours from randomization until patient discharge, and at the end of study visit (14 days after discharge or 14 days after end of study treatment, depending of what applies) | 
| Change in LDH | change from baseline in LDH levels | every 48h during hospitalization and end of study visit (14 days after discharge or 14 days after end of study treatment) | 
| Change in CPK | change from baseline in Creatin phosphokinase levels | every 48 hours from randomization until patient discharge, and at the end of study visit (14 days after discharge or 14 days after end of study treatment, depending of what applies) | 
| Change in D Dimer | change from baseline in D Dimer levels | every 48 hours from randomization until patient discharge, and at the end of study visit (14 days after discharge or 14 days after end of study treatment, depending of what applies) | 
| Change in IL-6 | change from baseline in IL-6 levels | Days 1, 8, 15 and end of study visit (14 days after discharge or 14 days after end of study treatment) | 
| Change in KL-6 | change from baseline in KL-6 levels | Days 1, 8, 15 and end of study visit (14 days after discharge or 14 days after end of study treatment) | 
| Change in Viral Load | COVID19 Viral load determination | Days 1,8,15 and end of study visit (14 days after discharge or 14 days after end of study treatment) | 
| Change specific antibodies | Specific IgG and IgM determination | Days 1,8,15 and end of study visit (14 days after discharge or 14 days after end of study treatment) |