Clinical trial NCT04979884: Safety and Effectiveness of Cyclosporin in the Management of COVID19 ARDS Patients in Alexandria University Hospital
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19 Acute Respiratory Distress Syndrome
Cytokine Release Syndrome
Pulmonary Fibrosis
Keywords: COVID-19
Cyclosporine
secondary haemophagocytic lymphohistiocytosis (sHLH)
acute respiratory distress syndrome (ARDS)
Lead sponsor: Alexandria University
Sponsor class: OTHER
Collaborators: name: Science and Technology Development Fund (STDF), ,Egypt
First posted: 2021-07-28
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

Eligibility criteria: 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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Primary outcomes:
measure: Percentage of subjects with a 6-point ordinal scale showing each severity level
timeFrame: 7-14 days after randomization
Secondary outcomes:
measure: Duration of hospital admission
timeFrame: through study completion, an average of 4 weeks
measure: Rate of decline OF Soluble interleukin-2 (IL-2) receptor alpha. (sCD25)
timeFrame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks)
measure: Rate of decline OF interleukin-1
timeFrame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks)
measure: Rate of decline OF interleukin-10(IL-10)
timeFrame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)
measure: Rate of decline OF Interleukin-6,( IL-6)
timeFrame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)
measure: Rate of decline OF Tumour necrosis factor α (TNFα)
timeFrame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)
measure: Time to 50% a decrease of ferritin levels compared to peak value during trial
timeFrame: up to 28 days
measure: Lung imaging improvement time
timeFrame: up to 28 days
measure: Time for non-invasive or invasive initial use
timeFrame: during hospital admission (up to 28 days)]
measure: Time to improvement in oxygenation
timeFrame: up to 28 days) from hospitalization
measure: Number of days safe from ventilators
timeFrame: during hospital admission (up to 28 days)
measure: Number of days on mechanical ventilation
timeFrame: during hospital admission (up to 28 days)
measure: Number of days in the intensive care unit after randomization
timeFrame: during hospital admission (up to 28 days)]
measure: Incidence of (Adverse Events) and Incidence of nosocomial bacterial or invasive fungal infection
timeFrame: during hospital admission (up to 28 days)]
measure: Mean change of SOFA score in ICU patients
timeFrame: between 1, 15 days) hospital discharge
measure: Mean improvement in Clinical Deterioration Changed Early Warning Score (MEWS) between 1, 15 days)
timeFrame: between 1, 15 days) hospital discharge
measure: rate of Mortality
timeFrame: throughout 30 and 90 days
measure: all-cause mortality will be measured.
timeFrame: At 28, 30, and 90 days,
Other outcomes:
Locations:
city: Alexandria
country: Egypt
facility: Alexandria university
Study officials:
affiliation: Alexandria University
name: Maged El-Setouhy
role: STUDY_DIRECTOR
References:
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.
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.
citation: 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.