COVID-19 Acute Respiratory Distress Syndrome, Cytokine Release Syndrome, Pulmonary Fibrosis
Conditions
Keywords
COVID-19, Cyclosporine, secondary haemophagocytic lymphohistiocytosis (sHLH), acute respiratory distress syndrome (ARDS)
Brief summary
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
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)
Interventions
DRUGcyclosporine
Dose of Cyclosporine oral capsule of 6 mg/kg/day divided into two doses with normal kidney function for 8-14 days
Sponsors
Science and Technology Development Fund (STDF), ,Egypt
Alexandria University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Current infection with COVID-19 2. written informed consent 3. 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. 4. 18yrs ≥ Age \<66 yrs 5. Chest X-ray showing suggestive of COVID-19 disease. 6. Both gender 7. The presence of Pulmonary fibrosis or hyper inflammation signs or A syndrome of cytokine release defined as any of the following:: 1. Leukopenia or lymphopenia, 2. Ferritin \> 500ng/mL or D-dimers ≥ 500 ng/mL 3. Hs\>90
Exclusion criteria
1. Lactation and Pregnancy women 2. unlikely to survive beyond 48h 3. Need for mechanical ventilation. 4. cases of multiorgan failure or abnormal renal function and shock. 5. malignancies, autoimmune disease, Perforation of the bowels or diverticulitis. 6. active bacterial or fungal infection. 7. 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. 8. Levels of serum transaminase \>5 upper references rang 9. Symptoms of active tuberculosis or human immunodeficiency virus (HIV) positivity 10. the patient receiving Vaccines: Live, attenuated vaccines 11. Subjects received monoclonal antibodies within one week before admission. 12. Patients receiving high-dose systemic steroids (\> 20 mg methylprednisolone or equivalent), immunosuppressant or immunomodulatory drugs 13. Contraindications for use in people with psoriasis include concomitant treatment with methotrexate, other immunosuppressant agents, coal tar, or radiation therapy. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of subjects with a 6-point ordinal scale showing each severity level | 7-14 days after randomization | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to improvement in oxygenation | up to 28 days) from hospitalization | defined as independence from supplemental oxygen |
| Number of days safe from ventilators | during hospital admission (up to 28 days) | efficacy of CSA in reducing days of ventilators |
| Duration of hospital admission | through study completion, an average of 4 weeks | efficacy of CsA (cyclosporine) in reducing days in hospital |
| Rate of decline OF Soluble interleukin-2 (IL-2) receptor alpha. (sCD25) | Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks) | change from baseline in IL-2 levels |
| Rate of decline OF interleukin-1 | Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks) | change from baseline in IL-1 levels |
| Rate of decline OF interleukin-10(IL-10) | Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks) | change from baseline in IL-10 levels |
| Rate of decline OF Interleukin-6,( IL-6) | Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks) | change from baseline in IL-6levels |
| Rate of decline OF Tumour necrosis factor α (TNFα) | Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks) | change from baseline in TNFα levels |
| Time to 50% a decrease of ferritin levels compared to peak value during trial | up to 28 days | change from baseline in ferritin levels |
| Lung imaging improvement time | up to 28 days | COVID19 Lung imaging determination |
| Time for non-invasive or invasive initial use | during hospital admission (up to 28 days)] | efficacy of CSA in reducing days of ventilators |
| Number of days on mechanical ventilation | during hospital admission (up to 28 days) | to evaluate the efficacy of CSA in reducing days of ventilators |
| Number of days in the intensive care unit after randomization | during hospital admission (up to 28 days)] | to evaluate the efficacy of CSA in reducing days in the intensive care unit |
| Incidence of (Adverse Events) and Incidence of nosocomial bacterial or invasive fungal infection | during hospital admission (up to 28 days)] | to evaluate the safety of CSA |
| Mean change of SOFA score in ICU patients | between 1, 15 days) hospital discharge | 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 |
| Mean improvement in Clinical Deterioration Changed Early Warning Score (MEWS) between 1, 15 days) | between 1, 15 days) hospital discharge | efficacy of CsA in Clinical improvement |
| rate of Mortality | throughout 30 and 90 days | efficacy of CsA in reducing mortality |
| all-cause mortality will be measured. | At 28, 30, and 90 days, | efficacy of CsA in reducing mortality |
Countries
Egypt
Outcome results
None listed