Clinical Trial to Assess Efficacy of cYclosporine Plus Standard of Care in Hospitalized Patients With COVID19

Open, Controlled, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Cyclosporine Plus Standard Treatment vs Standard Treatment Only in Hospitalized Patients With COVID-19 Infection

The study hypothesis is that cyclosporine, added to standard treatment of hospitalized patients with COVID19 infection may improve their prognosis.

Study Overview

• Status: Completed
• Conditions: COVID19 Infection
• Intervention / Treatment: Drug: Standard treatment; Drug: Cyclosporine

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain
    • Clínica Universitaria de Navarra
  • Galicia
    • La Coruña, Galicia, Spain
      • Complejo Hospitalario Universitario La Coruna
    • La Coruña, Galicia, Spain
      • Hospital Quiron La Coruña
  • Madrid
    • Mostoles, Madrid, Spain, 28933
      • Hospital Rey Juan Carlos
    • Valdemoro, Madrid, Spain, 28342
      • Hospital Infanta Elena
    • Villalba, Madrid, Spain, 28400
      • Hospital General de Villalba

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Women and men over 18 years old
2. Clinical diagnosis of COVID19 infection (to be subsequently confirmed by PCR or specific IgM isotype Ac and with entry criteria according to the protocol of action (see Annex 2)
3. Acceptance and signing of the consent for the study after having received the appropriate information.

Exclusion criteria

1. Known allergy or hypersensitivity to any of the medications included in the treatment arms or to any of their components.

2. Contraindication for the use of any of the medications included (*)

   • CsA: IR EST 4.5 (FG <30 ml / min according to the Cockcroft-Gault formula)
   • Antimalarials (Chloroquine, hydroxychloroquine): Retinopathy, Myasthenia gravis.
   • Lopinavir / ritonavir: severe liver failure
   • Remdesivir, darunovir-ritonavir
   • Doxycycline, Azithromycin
3. Kidney failure (Stages 4 and 5: GFR <30 ml / min according to the cockcroft-Gault formula).
4. Decompensated liver disease (Child-Pugh stages B or C) or chronic infection with virus B
5. Pregnancy or lactation
6. Age over 75 years
7. Participants in another clinical trial with medication in the 28 days prior to the start of recruitment. Participation in observational studies is allowed.
8. Refusal to participate
9. Patient with a poor state of health or nutrition who, in the opinion of the researcher, has sufficient criteria of severity to interfere with the development of the study or its conclusions
10. At the investigator's discretion, the patient's inability to understand or comply with the study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group A (control); The control group will consist on the standard treatment that patients will receive according to hospital standard of care protocol.	Drug: Standard treatment; Standard of care according to hospital protocol
EXPERIMENTAL: Group B (experimental); The experimental group will consist on cyclosporine added to the standard treatment that patients will receive according to hospital standard of care protocol.	Drug: Cyclosporine; In the experimental group, cyclosporine will be started according to patient weight, and then increased depending on patient tolerance (monitoring renal function and blood pressure)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity Category	efficacy of the association of CsA with standard treatment in reducing the severity of COVID19 infection in hospitalized patients.	12 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality Rate	efficacy of CsA in combination with standard treatment in reducing mortality	through study completion, an average of 6 weeks
Number of Days in hospital	efficacy of CsA in combination with standard treatment in reducing days in hospital	through study completion, an average of 6 weeks
Number of days in ICU beds	efficacy of CsA in combination with standard treatment in reducing days in ICU beds	through study completion, an average of 6 weeks
Fio2 Needs	efficacy of CsA in combination with standard treatment in reducing FiO2 needs.	through study completion, an average of 6 weeks
Adverse events rate	safety and tolerability of cyclosporine vs standard treatment administration	through study completion, an average of 6 weeks
Change in CRP	change from baseline in C reactive protein levels	every 48 hours from randomization until patient discharge, and at the end of study visit (14 days after discharge or 14 days after end of study treatment, depending of what applies)
Change in ferritin	change from baseline in ferritin levels	every 48 hours from randomization until patient discharge, and at the end of study visit (14 days after discharge or 14 days after end of study treatment, depending of what applies)
Change in LDH	change from baseline in LDH levels	every 48h during hospitalization and end of study visit (14 days after discharge or 14 days after end of study treatment)
Change in CPK	change from baseline in Creatin phosphokinase levels	every 48 hours from randomization until patient discharge, and at the end of study visit (14 days after discharge or 14 days after end of study treatment, depending of what applies)
Change in D Dimer	change from baseline in D Dimer levels	every 48 hours from randomization until patient discharge, and at the end of study visit (14 days after discharge or 14 days after end of study treatment, depending of what applies)
Change in IL-6	change from baseline in IL-6 levels	Days 1, 8, 15 and end of study visit (14 days after discharge or 14 days after end of study treatment)
Change in KL-6	change from baseline in KL-6 levels	Days 1, 8, 15 and end of study visit (14 days after discharge or 14 days after end of study treatment)
Change in Viral Load	COVID19 Viral load determination	Days 1,8,15 and end of study visit (14 days after discharge or 14 days after end of study treatment)
Change specific antibodies	Specific IgG and IgM determination	Days 1,8,15 and end of study visit (14 days after discharge or 14 days after end of study treatment)

Collaborators and Investigators

• Sponsor: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
• Investigators: Principal Investigator: Olga Sanchez Pernaute, MD, PhD, Fundacion Jimenez Diaz

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 16, 2020
• Primary Completion (ACTUAL): March 31, 2021
• Study Completion (ACTUAL): March 31, 2021

Study Registration Dates

• First Submitted: May 3, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (ACTUAL): May 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2022
• Last Update Submitted That Met QC Criteria: July 13, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: FJD-COVID19-20-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No