- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04979884
Safety and Effectiveness of Cyclosporin in the Management of COVID19 ARDS Patients in Alexandria University Hospital
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Ahmed Gad
- Phone Number: 00201144666619
- Email: ahmedyoussf0416@gmail.com
Study Locations
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Alexandria, Egypt, 21523
- Alexandria University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
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Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: cyclosporine
patients will receive cyclosporine + (standard care treatment (± anticoagulant± antibiotic± antipyretic± steroid) according to Alexandria university hospitals protocol )
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Dose of Cyclosporine oral capsule of 6 mg/kg/day divided into two doses with normal kidney function for 8-14 days
Other Names:
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Active Comparator: Standard of care treatment
patients will receive standard treatment (antiviral ± anticoagulant± antibiotic± antipyretic± steroid± interleukin ) according to Alexandria university hospitals protocol.
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Dose of Cyclosporine oral capsule of 6 mg/kg/day divided into two doses with normal kidney function for 8-14 days
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of subjects with a 6-point ordinal scale showing each severity level
Time Frame: 7-14 days after randomization
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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
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7-14 days after randomization
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of decline OF Soluble interleukin-2 (IL-2) receptor alpha. (sCD25)
Time Frame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks)
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change from baseline in IL-2 levels
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Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks)
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Rate of decline OF interleukin-1
Time Frame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks)
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change from baseline in IL-1 levels
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Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks)
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Rate of decline OF interleukin-10(IL-10)
Time Frame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)
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change from baseline in IL-10 levels
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Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)
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Rate of decline OF Interleukin-6,( IL-6)
Time Frame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)
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change from baseline in IL-6levels
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Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)
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Rate of decline OF Tumour necrosis factor α (TNFα)
Time Frame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)
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change from baseline in TNFα levels
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Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)
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Time to 50% a decrease of ferritin levels compared to peak value during trial
Time Frame: up to 28 days
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change from baseline in ferritin levels
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up to 28 days
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Lung imaging improvement time
Time Frame: up to 28 days
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COVID19 Lung imaging determination
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up to 28 days
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Time for non-invasive or invasive initial use
Time Frame: during hospital admission (up to 28 days)]
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efficacy of CSA in reducing days of ventilators
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during hospital admission (up to 28 days)]
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Time to improvement in oxygenation
Time Frame: up to 28 days) from hospitalization
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defined as independence from supplemental oxygen
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up to 28 days) from hospitalization
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Number of days safe from ventilators
Time Frame: during hospital admission (up to 28 days)
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efficacy of CSA in reducing days of ventilators
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during hospital admission (up to 28 days)
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Number of days on mechanical ventilation
Time Frame: during hospital admission (up to 28 days)
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to evaluate the efficacy of CSA in reducing days of ventilators
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during hospital admission (up to 28 days)
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Number of days in the intensive care unit after randomization
Time Frame: during hospital admission (up to 28 days)]
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to evaluate the efficacy of CSA in reducing days in the intensive care unit
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during hospital admission (up to 28 days)]
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Incidence of (Adverse Events) and Incidence of nosocomial bacterial or invasive fungal infection
Time Frame: during hospital admission (up to 28 days)]
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to evaluate the safety of CSA
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during hospital admission (up to 28 days)]
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Mean change of SOFA score in ICU patients
Time Frame: between 1, 15 days) hospital discharge
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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
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between 1, 15 days) hospital discharge
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Mean improvement in Clinical Deterioration Changed Early Warning Score (MEWS) between 1, 15 days)
Time Frame: between 1, 15 days) hospital discharge
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efficacy of CsA in Clinical improvement
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between 1, 15 days) hospital discharge
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rate of Mortality
Time Frame: throughout 30 and 90 days
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efficacy of CsA in reducing mortality
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throughout 30 and 90 days
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all-cause mortality will be measured.
Time Frame: At 28, 30, and 90 days,
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efficacy of CsA in reducing mortality
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At 28, 30, and 90 days,
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Duration of hospital admission
Time Frame: through study completion, an average of 4 weeks
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efficacy of CsA (cyclosporine) in reducing days in hospital
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through study completion, an average of 4 weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Maged El-Setouhy, Alexandria University
Publications and helpful links
General Publications
- Fellman CL, Archer TM, Wills RW, Mackin AJ. Effects of cyclosporine and dexamethasone on canine T cell expression of interleukin-2 and interferon-gamma. Vet Immunol Immunopathol. 2019 Oct;216:109892. doi: 10.1016/j.vetimm.2019.109892. Epub 2019 Jul 11.
- Damaso CR, Keller SJ. Cyclosporin A inhibits vaccinia virus replication in vitro. Arch Virol. 1994;134(3-4):303-19. doi: 10.1007/BF01310569.
- Ciesek S, Steinmann E, Wedemeyer H, Manns MP, Neyts J, Tautz N, Madan V, Bartenschlager R, von Hahn T, Pietschmann T. Cyclosporine A inhibits hepatitis C virus nonstructural protein 2 through cyclophilin A. Hepatology. 2009 Nov;50(5):1638-45. doi: 10.1002/hep.23281.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Respiration Disorders
- Pneumonia, Viral
- Pneumonia
- Lung Diseases
- Systemic Inflammatory Response Syndrome
- Inflammation
- Disease
- Infant, Newborn, Diseases
- Shock
- Fibrosis
- Lung Diseases, Interstitial
- Lung Injury
- Infant, Premature, Diseases
- COVID-19
- Syndrome
- Pulmonary Fibrosis
- Respiratory Distress Syndrome
- Respiratory Distress Syndrome, Newborn
- Acute Lung Injury
- Cytokine Release Syndrome
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Antifungal Agents
- Calcineurin Inhibitors
- Cyclosporine
- Cyclosporins
- Interleukin-2
Other Study ID Numbers
- cyclosporine in COVID-19
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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