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

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

Study Overview

• Status: Completed
• Conditions: Pulmonary Fibrosis; Cytokine Release Syndrome; COVID-19 Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: cyclosporine

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: Interventional
• Enrollment (Actual): 66
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt, 21523
    • Alexandria University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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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)

Number of Arms

2

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 )	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

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	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
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,
Duration of hospital admission	efficacy of CsA (cyclosporine) in reducing days in hospital	through study completion, an average of 4 weeks

Collaborators and Investigators

• Sponsor: Alexandria University
• Collaborators: Science and Technology Development Fund (STDF), ,Egypt
• 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): January 3, 2022
• Primary Completion (Actual): September 9, 2022
• Study Completion (Actual): December 9, 2022

Study Registration Dates

• First Submitted: July 14, 2021
• First Submitted That Met QC Criteria: July 26, 2021
• First Posted (Actual): July 28, 2021

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; Cyclosporine; acute respiratory distress syndrome (ARDS); secondary haemophagocytic lymphohistiocytosis (sHLH)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Disease; Systemic Inflammatory Response Syndrome; Inflammation; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Lung Diseases, Interstitial; Fibrosis; Shock; Lung Injury; COVID-19; Cytokine Release Syndrome; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Pulmonary Fibrosis; Acute Lung Injury; Anti-Infective Agents; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Dermatologic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Calcineurin Inhibitors; Cyclosporine; Cyclosporins; Interleukin-2
• Other Study ID Numbers: cyclosporine in COVID-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes