Safety and Effectiveness of Cyclosporin in the Management of COVID19 ARDS Patients in Alexandria University Hospital

Study Overview
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Brief Summary
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The study to evaluate the effect of cyclosporine ( IL2 inhibitor and antiviral) verse standard care treatment on decrease ADRS, hyper inflammation, hypercytokinemia, and the mortality rate

Detailed Description
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To test the efficacy of IL-2 inhibitors (Cyclosporine) compared to the Standard of care according to hospital protocol on COVID-19 patients concerning the clinical outcome (cytokines level, clinical improvement, and PCR of SARS-CoV-2 through the study period). AIM: The slow progression of the disease, improving survival among COVID-19 patients, and Standard assessment of patient improvement. Standard assessment of patient improvement: PCR-SARS-CoV-2 negative No fever No cytopenia (Hb ≥90 g/L, ANC ≥0.5x109/L, platelets ≥100x109/L) • No hyperferritinemia ≥500 μg/L (Decrease of IL2)

Official Title
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Safety and Therapeutic Efficacy of Cyclosporine Plus Standard of Care Treatment on ARDS in COVID -19 Patients at Alexandria University Hospitals in 2021: a Comparative Study

Conditions
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COVID-19 Acute Respiratory Distress Syndrome, Cytokine Release Syndrome, Pulmonary Fibrosis

Intervention / Treatment
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* Drug: cyclosporine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current infection with COVID-19 written informed consent Confirmed diagnosis of COVID-19 by PCR (polymerase chain reaction) tests and/or Positive Serology or any existing and validated diagnostic COVID-19 parameters during this time. 18yrs ≥ Age <66 yrs Chest X-ray showing suggestive of COVID-19 disease. Both gender The presence of Pulmonary fibrosis or hyper inflammation signs or A syndrome of cytokine release defined as any of the following:: Leukopenia or lymphopenia, Ferritin > 500ng/mL or D-dimers ≥ 500 ng/mL Hs>90 Exclusion Criteria: Lactation and Pregnancy women unlikely to survive beyond 48h Need for mechanical ventilation. cases of multiorgan failure or abnormal renal function and shock. malignancies, autoimmune disease, Perforation of the bowels or diverticulitis. active bacterial or fungal infection. We define impairment of cardiac function as poorly controlled heart diseases, cardiac insufficiency, unstable angina pectoris, myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia needs treatment or intervention, Uncontrolled hypertension (>180/110 mmHg. Levels of serum transaminase >5 upper references rang Symptoms of active tuberculosis or human immunodeficiency virus (HIV) positivity the patient receiving Vaccines: Live, attenuated vaccines Subjects received monoclonal antibodies within one week before admission. Patients receiving high-dose systemic steroids (> 20 mg methylprednisolone or equivalent), immunosuppressant or immunomodulatory drugs Contraindications for use in people with psoriasis include concomitant treatment with methotrexate, other immunosuppressant agents, coal tar, or radiation therapy. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Experimental: cyclosporine<br>patients will receive cyclosporine + (standard care treatment (± anticoagulant± antibiotic± antipyretic± steroid) according to Alexandria university hospitals protocol ) | Drug: cyclosporine<br>* Dose of Cyclosporine oral capsule of 6 mg/kg/day divided into two doses with normal kidney function for 8-14 days<br>* Other names: interleukin-2;|
| Active Comparator: Standard of care treatment<br>patients will receive standard treatment (antiviral ± anticoagulant± antibiotic± antipyretic± steroid± interleukin ) according to Alexandria university hospitals protocol. | Drug: cyclosporine<br>* Dose of Cyclosporine oral capsule of 6 mg/kg/day divided into two doses with normal kidney function for 8-14 days<br>* Other names: interleukin-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with a 6-point ordinal scale showing each severity level | i. Death ii. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation iii. Hospitalized, on non-invasive ventilation or high flow oxygen devices iv. Hospitalized, requiring supplemental oxygen v. Hospitalized, not requiring supplemental oxygen vi. Not hospitalized | 7-14 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of hospital admission | efficacy of CsA (cyclosporine) in reducing days in hospital | through study completion, an average of 4 weeks | 
| Rate of decline OF Soluble interleukin-2 (IL-2) receptor alpha. (sCD25) | change from baseline in IL-2 levels | Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks) | 
| Rate of decline OF interleukin-1 | change from baseline in IL-1 levels | Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks) | 
| Rate of decline OF interleukin-10(IL-10) | change from baseline in IL-10 levels | Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks) | 
| Rate of decline OF Interleukin-6,( IL-6) | change from baseline in IL-6levels | Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks) | 
| Rate of decline OF Tumour necrosis factor α (TNFα) | change from baseline in TNFα levels | Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks) | 
| Time to 50% a decrease of ferritin levels compared to peak value during trial | change from baseline in ferritin levels | up to 28 days | 
| Lung imaging improvement time | COVID19 Lung imaging determination | up to 28 days | 
| Time for non-invasive or invasive initial use | efficacy of CSA in reducing days of ventilators | during hospital admission (up to 28 days)] | 
| Time to improvement in oxygenation | defined as independence from supplemental oxygen | up to 28 days) from hospitalization | 
| Number of days safe from ventilators | efficacy of CSA in reducing days of ventilators | during hospital admission (up to 28 days) | 
| Number of days on mechanical ventilation | to evaluate the efficacy of CSA in reducing days of ventilators | during hospital admission (up to 28 days) | 
| Number of days in the intensive care unit after randomization | to evaluate the efficacy of CSA in reducing days in the intensive care unit | during hospital admission (up to 28 days)] | 
| Incidence of (Adverse Events) and Incidence of nosocomial bacterial or invasive fungal infection | to evaluate the safety of CSA | during hospital admission (up to 28 days)] | 
| Mean change of SOFA score in ICU patients | The Sequential Organ Failure Assessment (SOFA) score: 0 (best) - 24 (worse) The SOFA score will be used to assess the probability of organ failure and mortality in ICU patients | between 1, 15 days) hospital discharge | 
| Mean improvement in Clinical Deterioration Changed Early Warning Score (MEWS) between 1, 15 days) | efficacy of CsA in Clinical improvement | between 1, 15 days) hospital discharge | 
| rate of Mortality | efficacy of CsA in reducing mortality | throughout 30 and 90 days | 
| all-cause mortality will be measured. | efficacy of CsA in reducing mortality | At 28, 30, and 90 days, | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Cyclosporine, secondary haemophagocytic lymphohistiocytosis (sHLH), acute respiratory distress syndrome (ARDS)