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

Phase 3

Completed

• Conditions: COVID-19 Acute Respiratory Distress Syndrome; Cytokine Release Syndrome; Pulmonary Fibrosis
• Interventions: Drug: cyclosporine

• Registration Number: NCT04979884
• Lead Sponsor: Alexandria University

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)

Study Timeline

• Status Verified: 2021-07
• Study First Submitted: 2021-07-14
• Study First Submitted QC: 2021-07-26
• Study First Posted: 2021-07-28
• Study Start: 2022-01-03
• Primary Completion: 2022-09-09
• Study Completion: 2022-12-09
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care treatment	cyclosporine	patients will receive standard treatment (antiviral ± anticoagulant± antibiotic± antipyretic± steroid± interleukin ) according to Alexandria university hospitals protocol.
cyclosporine	cyclosporine	patients will receive cyclosporine + (standard care treatment (± anticoagulant± antibiotic± antipyretic± steroid) according to Alexandria university hospitals protocol )

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
all-cause mortality will be measured.	At 28, 30, and 90 days,	efficacy of CsA in reducing mortality
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-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 improvement in oxygenation	up to 28 days) from hospitalization	defined as independence from supplemental oxygen
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
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 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
Time to 50% a decrease of ferritin levels compared to peak value during trial	up to 28 days	change from baseline in ferritin levels
Number of days safe from ventilators	during hospital admission (up to 28 days)	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
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
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

Trial Locations

Locations (1)

Alexandria university; 🇪🇬 Alexandria, Egypt