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

Sponsor

Alexandria University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04979884

Collaborator

Science and Technology Development Fund (STDF), ,Egypt (Other)

150

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Acute Respiratory Distress Syndrome Cytokine Release Syndrome Pulmonary Fibrosis	Drug: cyclosporine	Phase 3

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)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2021

Anticipated Primary Completion Date :

Feb 1, 2022

Anticipated Study Completion Date :

Apr 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: cyclosporine patients will receive cyclosporine + (standard care treatment (± anticoagulant± antibiotic± antipyretic± steroid) according to Alexandria university hospitals protocol )	Drug: cyclosporine Dose of Cyclosporine oral capsule of 6 mg/kg/day divided into two doses with normal kidney function for 8-14 days Other Names: interleukin-2
Active Comparator: Standard of care treatment patients will receive standard treatment (antiviral ± anticoagulant± antibiotic± antipyretic± steroid± interleukin ) according to Alexandria university hospitals protocol.	Drug: cyclosporine Dose of Cyclosporine oral capsule of 6 mg/kg/day divided into two doses with normal kidney function for 8-14 days Other Names: interleukin-2

Arm

Intervention/Treatment

Experimental: cyclosporine

patients will receive cyclosporine + (standard care treatment (± anticoagulant± antibiotic± antipyretic± steroid) according to Alexandria university hospitals protocol )

Drug: cyclosporine

Dose of Cyclosporine oral capsule of 6 mg/kg/day divided into two doses with normal kidney function for 8-14 days

Other Names:

interleukin-2

Active Comparator: Standard of care treatment

patients will receive standard treatment (antiviral ± anticoagulant± antibiotic± antipyretic± steroid± interleukin ) according to Alexandria university hospitals protocol.

Drug: cyclosporine

Dose of Cyclosporine oral capsule of 6 mg/kg/day divided into two doses with normal kidney function for 8-14 days

Other Names:

interleukin-2

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Duration of hospital admission [through study completion, an average of 4 weeks]
efficacy of CsA 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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Current infection with COVID-19
written informed consent
Confirmed diagnosis of COVID-19 by PCR 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.