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

Primary Purpose

COVID-19 Acute Respiratory Distress Syndrome, Cytokine Release Syndrome, Pulmonary Fibrosis

Status

Completed

Phase

Phase 3

Locations

Egypt

Study Type

Interventional

Intervention

cyclosporine

About this trial

This is an interventional treatment trial for COVID-19 Acute Respiratory Distress Syndrome focused on measuring COVID-19, Cyclosporine, secondary haemophagocytic lymphohistiocytosis (sHLH), acute respiratory distress syndrome (ARDS)

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Current infection with COVID-19
written informed consent
Confirmed diagnosis of COVID-19 by PCR 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::
1. Leukopenia or lymphopenia,
2. Ferritin > 500ng/mL or D-dimers ≥ 500 ng/mL
3. 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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Sites / Locations

Alexandria university

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

cyclosporine

Standard of care treatment

Arm Description

patients will receive cyclosporine + (standard care treatment (± anticoagulant± antibiotic± antipyretic± steroid) according to Alexandria university hospitals protocol )

patients will receive standard treatment (antiviral ± anticoagulant± antibiotic± antipyretic± steroid± interleukin ) according to Alexandria university hospitals protocol.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Duration of hospital admission

efficacy of CsA (cyclosporine) in reducing days in hospital

Rate of decline OF Soluble interleukin-2 (IL-2) receptor alpha. (sCD25)

change from baseline in IL-2 levels

Rate of decline OF interleukin-1

change from baseline in IL-1 levels

Rate of decline OF interleukin-10(IL-10)

change from baseline in IL-10 levels

Rate of decline OF Interleukin-6,( IL-6)

change from baseline in IL-6levels

Rate of decline OF Tumour necrosis factor α (TNFα)

change from baseline in TNFα levels

Time to 50% a decrease of ferritin levels compared to peak value during trial

change from baseline in ferritin levels

Lung imaging improvement time

COVID19 Lung imaging determination

Time for non-invasive or invasive initial use

efficacy of CSA in reducing days of ventilators

Time to improvement in oxygenation

defined as independence from supplemental oxygen

Number of days safe from ventilators

efficacy of CSA in reducing days of ventilators

Number of days on mechanical ventilation

to evaluate the efficacy of CSA in reducing days of ventilators

Number of days in the intensive care unit after randomization

to evaluate the efficacy of CSA in reducing days in the intensive care unit

Incidence of (Adverse Events) and Incidence of nosocomial bacterial or invasive fungal infection

to evaluate the safety of CSA

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

Mean improvement in Clinical Deterioration Changed Early Warning Score (MEWS) between 1, 15 days)

efficacy of CsA in Clinical improvement

rate of Mortality

efficacy of CsA in reducing mortality

all-cause mortality will be measured.

efficacy of CsA in reducing mortality

Full Information

NCT ID

NCT04979884

First Posted

July 14, 2021

Last Updated

July 24, 2023

Sponsor

Alexandria University

Collaborators

Science and Technology Development Fund (STDF), ,Egypt

1. Study Identification

Unique Protocol Identification Number

NCT04979884

Brief Title

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

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

January 3, 2022 (Actual)

Primary Completion Date

September 9, 2022 (Actual)

Study Completion Date

December 9, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alexandria University

Collaborators

Science and Technology Development Fund (STDF), ,Egypt

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19 Acute Respiratory Distress Syndrome, Cytokine Release Syndrome, Pulmonary Fibrosis

Keywords

COVID-19, Cyclosporine, secondary haemophagocytic lymphohistiocytosis (sHLH), acute respiratory distress syndrome (ARDS)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

102 (Actual)

8. Arms, Groups, and Interventions

Arm Title

cyclosporine

Arm Type

Experimental

Arm Description

patients will receive cyclosporine + (standard care treatment (± anticoagulant± antibiotic± antipyretic± steroid) according to Alexandria university hospitals protocol )

Arm Title

Standard of care treatment

Arm Type

Active Comparator

Arm Description

patients will receive standard treatment (antiviral ± anticoagulant± antibiotic± antipyretic± steroid± interleukin ) according to Alexandria university hospitals protocol.

Intervention Type

Drug

Intervention Name(s)

cyclosporine

Other Intervention Name(s)

interleukin-2

Intervention Description

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

Primary Outcome Measure Information:

Title

Percentage of subjects with a 6-point ordinal scale showing each severity level

Description

Time Frame

7-14 days after randomization

Secondary Outcome Measure Information:

Title

Duration of hospital admission

Description

efficacy of CsA (cyclosporine) in reducing days in hospital

Time Frame

through study completion, an average of 4 weeks

Title

Rate of decline OF Soluble interleukin-2 (IL-2) receptor alpha. (sCD25)

Description

change from baseline in IL-2 levels

Time Frame

Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks)

Title

Rate of decline OF interleukin-1

Description

change from baseline in IL-1 levels

Time Frame

Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks)

Title

Rate of decline OF interleukin-10(IL-10)

Description

change from baseline in IL-10 levels

Time Frame

Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)

Title

Rate of decline OF Interleukin-6,( IL-6)

Description

change from baseline in IL-6levels

Time Frame

Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)

Title

Rate of decline OF Tumour necrosis factor α (TNFα)

Description

change from baseline in TNFα levels

Time Frame

Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)

Title

Time to 50% a decrease of ferritin levels compared to peak value during trial

Description

change from baseline in ferritin levels

Time Frame

up to 28 days

Title

Lung imaging improvement time

Description

COVID19 Lung imaging determination

Time Frame

up to 28 days

Title

Time for non-invasive or invasive initial use

Description

efficacy of CSA in reducing days of ventilators

Time Frame

during hospital admission (up to 28 days)]

Title

Time to improvement in oxygenation

Description

defined as independence from supplemental oxygen

Time Frame

up to 28 days) from hospitalization

Title

Number of days safe from ventilators

Description

efficacy of CSA in reducing days of ventilators

Time Frame

during hospital admission (up to 28 days)

Title

Number of days on mechanical ventilation

Description

to evaluate the efficacy of CSA in reducing days of ventilators

Time Frame

during hospital admission (up to 28 days)

Title

Number of days in the intensive care unit after randomization

Description

to evaluate the efficacy of CSA in reducing days in the intensive care unit

Time Frame

during hospital admission (up to 28 days)]

Title

Incidence of (Adverse Events) and Incidence of nosocomial bacterial or invasive fungal infection

Description

to evaluate the safety of CSA

Time Frame

during hospital admission (up to 28 days)]

Title

Mean change of SOFA score in ICU patients

Description

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

Time Frame

between 1, 15 days) hospital discharge

Title

Mean improvement in Clinical Deterioration Changed Early Warning Score (MEWS) between 1, 15 days)

Description

efficacy of CsA in Clinical improvement

Time Frame

between 1, 15 days) hospital discharge

Title

rate of Mortality

Description

efficacy of CsA in reducing mortality

Time Frame

throughout 30 and 90 days

Title

all-cause mortality will be measured.

Description

efficacy of CsA in reducing mortality

Time Frame

At 28, 30, and 90 days,

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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. -

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Maged El-Setouhy

Organizational Affiliation

Alexandria University

Official's Role

Study Director

Facility Information:

Facility Name

Alexandria university

City

Alexandria

ZIP/Postal Code

21523

Country

Egypt

12. IPD Sharing Statement

Citations:

PubMed Identifier

31446206

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.

Results Reference

background

PubMed Identifier

8129618

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.

Results Reference

background

PubMed Identifier

19821520

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.

Results Reference

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

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