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

Pulmonary Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04979884
• Other study ID #: cyclosporine in COVID-19
• Status: Completed
• Phase: Phase 3
• Start date: January 3, 2022
• Est. completion date: December 9, 2022

Study information

• Verified date: July 2021
• Source: Alexandria University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: December 9, 2022
• Est. primary completion date: September 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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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Related Conditions & MeSH terms

• Acute Lung Injury
• COVID-19
• Cytokine Release Syndrome
• Pulmonary Fibrosis
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

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

Locations

Country	Name	City	State
Egypt	Alexandria university	Alexandria

Sponsors (2)

Lead Sponsor	Collaborator
Alexandria University	Science and Technology Development Fund (STDF), ,Egypt

Country where clinical trial is conducted

Egypt, 

References & Publications (3)

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. — View Citation

Damaso CR, Keller SJ. Cyclosporin A inhibits vaccinia virus replication in vitro. Arch Virol. 1994;134(3-4):303-19. doi: 10.1007/BF01310569. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Duration of hospital admission	efficacy of CsA (cyclosporine) in reducing days in hospital	through study completion, an average of 4 weeks
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Rate of decline OF Tumour necrosis factor a (TNFa)	change from baseline in TNFa levels	Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)
Secondary	Time to 50% a decrease of ferritin levels compared to peak value during trial	change from baseline in ferritin levels	up to 28 days
Secondary	Lung imaging improvement time	COVID19 Lung imaging determination	up to 28 days
Secondary	Time for non-invasive or invasive initial use	efficacy of CSA in reducing days of ventilators	during hospital admission (up to 28 days)]
Secondary	Time to improvement in oxygenation	defined as independence from supplemental oxygen	up to 28 days) from hospitalization
Secondary	Number of days safe from ventilators	efficacy of CSA in reducing days of ventilators	during hospital admission (up to 28 days)
Secondary	Number of days on mechanical ventilation	to evaluate the efficacy of CSA in reducing days of ventilators	during hospital admission (up to 28 days)
Secondary	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)]
Secondary	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)]
Secondary	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
Secondary	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
Secondary	rate of Mortality	efficacy of CsA in reducing mortality	throughout 30 and 90 days
Secondary	all-cause mortality will be measured.	efficacy of CsA in reducing mortality	At 28, 30, and 90 days,