COVID-19 Acute Respiratory Distress SyndromePhase 3NCT04979884
Safety and Effectiveness of Cyclosporin in the Management of COVID19 ARDS Patients in Alexandria University Hospital
A Phase 3 study testing cyclosporine in people with COVID-19 Acute Respiratory Distress Syndrome and Cytokine Release Syndrome, run by Alexandria University at 1 site in Egypt.
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 Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- COVID-19 Acute Respiratory Distress Syndrome, Cytokine Release Syndrome, Pulmonary Fibrosis
- What is being tested?
- cyclosporine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteEgypt
- Study dates
- 3 Jan 2022to 9 Dec 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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.
- -
Trial locations and contacts
1 site in 1 country.
About this study
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
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
Read the 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)
- Conditions
- COVID-19 Acute Respiratory Distress Syndrome, Cytokine Release Syndrome, Pulmonary Fibrosis
- Being tested
- cyclosporine
- Keywords
- COVID-19, Cyclosporine, secondary haemophagocytic lymphohistiocytosis (sHLH), acute respiratory distress syndrome (ARDS)
- Medical subject headings
- Cytokine Release Syndrome, Pulmonary Fibrosis, COVID-19, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclosporineDrug
Also called interleukin-2
Dose of Cyclosporine oral capsule of 6 mg/kg/day divided into two doses with normal kidney function for 8-14 days
| Study group | Role | What they receive |
|---|---|---|
| cyclosporine | Experimental | patients will receive cyclosporine + (standard care treatment (± anticoagulant± antibiotic± antipyretic± steroid) according to Alexandria university hospitals protocol ) Receives: Drug: cyclosporine |
| Standard of care treatment | Active comparator | patients will receive standard treatment (antiviral ± anticoagulant± antibiotic± antipyretic± steroid± interleukin ) according to Alexandria university hospitals protocol. Receives: Drug: cyclosporine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of subjects with a 6-point ordinal scale showing each severity level
- 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
Measured: 7-14 days after randomization
Secondary outcomes (18)
Duration of hospital admission
efficacy of CsA (cyclosporine) in reducing days in hospital
Measured: through study completion, an average of 4 weeks
Rate of decline OF Soluble interleukin-2 (IL-2) receptor alpha. (sCD25)
change from baseline in IL-2 levels
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: up to 28 days
Lung imaging improvement time
COVID19 Lung imaging determination
Measured: up to 28 days
Time for non-invasive or invasive initial use
efficacy of CSA in reducing days of ventilators
Measured: during hospital admission (up to 28 days)]
Time to improvement in oxygenation
defined as independence from supplemental oxygen
Measured: up to 28 days) from hospitalization
Number of days safe from ventilators
efficacy of CSA in reducing days of ventilators
Measured: during hospital admission (up to 28 days)
Number of days on mechanical ventilation
to evaluate the efficacy of CSA in reducing days of ventilators
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: between 1, 15 days) hospital discharge
rate of Mortality
efficacy of CsA in reducing mortality
Measured: throughout 30 and 90 days
all-cause mortality will be measured.
efficacy of CsA in reducing mortality
Measured: At 28, 30, and 90 days,
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2021
- Study start3 Jan 2022
- Primary completion9 Sep 2022
- Study completion9 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for COVID-19 Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by Alexandria UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexandria University
- Sponsor type
- University, hospital or other
- Collaborators
- Science and Technology Development Fund (STDF), ,Egypt
- Responsible party
- Sponsor
- Investigators
- Maged El-Setouhy, Study director, Alexandria University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04979884
- Sponsor's protocol ID
- cyclosporine in COVID-19
- Status last verified
- Jul 2021
- First submitted
- 14 Jul 2021
- Last updated
- 14 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 31446206Damaso CR, Keller SJ. Cyclosporin A inhibits vaccinia virus replication in vitro. Arch Virol. 1994;134(3-4):303-19. doi: 10.1007/BF01310569.
PubMed 8129618Ciesek 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.
PubMed 19821520
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04979884
- Acronym / sponsor ID
- cyclosporine in COVID-19
- 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)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Alexandria UniversityUniversity, hospital or other
- Collaborators
- Science and Technology Development Fund (STDF), ,Egypt
- Study start
- 3 Jan 2022 (actual)
- Primary completion
- 9 Sep 2022 (actual)
- Study completion
- 9 Dec 2022 (actual)
- First posted
- 28 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cyclosporine | Experimental | Drug: cyclosporinepatients will receive cyclosporine + (standard care treatment (± anticoagulant± antibiotic± antipyretic± steroid) according to Alexandria university hospitals protocol ) |
| Standard of care treatment | Active comparator | Drug: cyclosporinepatients will receive standard treatment (antiviral ± anticoagulant± antibiotic± antipyretic± steroid± interleukin ) according to Alexandria university hospitals protocol. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclosporineAlso: interleukin-2Dose of Cyclosporine oral capsule of 6 mg/kg/day divided into two doses with normal kidney function for 8-14 days | Drug | Standard of care treatment, cyclosporine |
Primary outcome
Percentage of subjects with a 6-point ordinal scale showing each severity level
Time frame: 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
18 secondary outcomes
Duration of hospital admission
Time frame: through study completion, an average of 4 weeks
Rate of decline OF Soluble interleukin-2 (IL-2) receptor alpha. (sCD25)
Time frame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks)
Rate of decline OF interleukin-1
Time frame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 6 weeks)
Rate of decline OF interleukin-10(IL-10)
Time frame: Days 1, 8, 15 or at hospital discharge(through study completion, an average of 4 weeks)
Rate of decline OF Interleukin-6,( IL-6)
Time frame: 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)
Time frame: 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
Time frame: up to 28 days
Lung imaging improvement time
Time frame: up to 28 days
Time for non-invasive or invasive initial use
Time frame: during hospital admission (up to 28 days)]
Time to improvement in oxygenation
Time frame: up to 28 days) from hospitalization
Number of days safe from ventilators
Time frame: during hospital admission (up to 28 days)
Number of days on mechanical ventilation
Time frame: during hospital admission (up to 28 days)
Number of days in the intensive care unit after randomization
Time frame: during hospital admission (up to 28 days)]
Incidence of (Adverse Events) and Incidence of nosocomial bacterial or invasive fungal infection
Time frame: during hospital admission (up to 28 days)]
Mean change of SOFA score in ICU patients
Time frame: between 1, 15 days) hospital discharge
Mean improvement in Clinical Deterioration Changed Early Warning Score (MEWS) between 1, 15 days)
Time frame: between 1, 15 days) hospital discharge
rate of Mortality
Time frame: throughout 30 and 90 days
all-cause mortality will be measured.
Time frame: At 28, 30, and 90 days,
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Background: PubMed 31446206Fellman 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.
- Background: PubMed 8129618Damaso CR, Keller SJ. Cyclosporin A inhibits vaccinia virus replication in vitro. Arch Virol. 1994;134(3-4):303-19. doi: 10.1007/BF01310569.
- Background: PubMed 19821520Ciesek 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maged El-Setouhy study director
Alexandria University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing cyclosporine in people with COVID-19 Acute Respiratory Distress Syndrome and Cytokine Release Syndrome, run by Alexandria University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of subjects with a 6-point ordinal scale showing each severity level (time frame: 7-14 days after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04979884, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.