SARS-CoV-2 infection causing respiratory disease and cytokine release syndrome MedDRA version: 20.0 Level: LLT Classification code 10051905 Term: Coronavirus infection System Organ Class: 100000004862 MedDRA version: 21.1 Level: PT Classification code 10001052 Term: Acute respiratory distress syndrome System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Kevzara 200mg
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: SARILUMAB
CAS Number: 1189541-98-7
Concentration unit: mg/ml milligram(s)/millilitre
Concen
Sponsors
Fundación para la Investigación Biomédica de Córdoba
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years and 40 pg / ml. In its absence, D-Dimer (DD)> 1500 or> 1000 may be included if progressive increases are documented 5. Negative pregnancy test in women of childbearing age 6. Signature of informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. SOFA score> 6 points 2. Patient who, in the researcher's opinion, is not a subsidiary of invasive mechanical ventilation 3. Neutrophil count 5 times the upper limit of normal 6. Severe renal failure (CrCr <30 ml / min) 7. Active bacterial infectious process 8. Active tuberculosis, history of not completing treatment against tuberculosis, suspicion of extrapulmonary tuberculosis 9. History of intestinal ulcer or diverticulitis 10. History of hypersensitivity reactions to Sarilumab or its excipients 11. Treatment with TNF antagonists 13. Previous treatment with anti-IL6 in the previous 30 days 14. Chronic prior treatment with corticosteroids at doses greater than 0.5 mg / kg / day of prednisone or equivalent. Yes, inhaled and topical corticosteroids are acceptable 15. Concomitant treatment with immunomodulators, among which are Vitamin D or statins. Macrolides such as azithromycin are acceptable 16. Patients on immunosuppressive treatment for any cause 17. HIV-infected patients with CD4 <200 / mm3 18. Past or current history of autoimmune disease or systemic inflammatory disease 19. Patients who have received or are planning therapy with immunomodulatory antibodies, including immunoglobulins 20. Participation in any clinical trial that evaluated any investigational product in the last 3 months or less than 5 half-lives of the investigational product 21. Pregnancy 22. Any other condition that, in clinical judgment, prevents adherence to the patient's protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Decrease cases of ARDS in adults requiring HFNO or either non-invasive or invasive mechanical ventilation;Secondary Objective: To reduce crude mortality at 28 days To reduce the time (in days) to clinical improvement To reduce the time (in days) until improvement in oxygenation for at least 48 hours To reduce the proportion of patients who require invasive mechanical ventilation To study the effect of the drug on the negativization of the PCR to COVID-19 To study the effect of the drug on the profile of cytokines To study the safety of the experimental drug;Primary end point(s): Proportion of patients requiring or time (in days) until required: - High flow nasal oxygenation (HFNO) - Non-invasive mechanical ventilation type BiPAP - Non-invasive mechanical ventilation type CPAP - Invasive mechanical ventilation;Timepoint(s) of evaluation of this end point: At day 28 or when the subject is discharged (whichever occurs first) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a. Crude mortality at 28 days b. Time to clinical improvement: defined as the mean change or time in days from randomization to any of the following criteria: (i) improvement of two points on the ordinal scale of 7 points of severity or, (ii) hospital discharge with lifetime. The criteria reached before are used. The 7 point gravity scale includes the following categories: 1 - Not hospitalized with normal activity 2 - Not hospitalized but unable to have normal activity 3 - Hospitalized, without requiring oxygen supplementation 4 - Hospitalized, requiring oxygen supplementation 5 - Hospitalized, requiring ONAF, non-invasive mechanical ventilation or both 6 - Hospitalized requiring ECMO, invasive mechanical ventilation or both 7 - Death c. Time (in days) until improvement in oxygenation for at least 48 hours: - Time to verify an increase in the SpO2 / FiO2 ratio with respect to the worst SpO2 / FiO2 prior to treatment with Sarilumab and stratified according to levels of IL-6 or DD - Time to absence of oxygen requirement to maintain saturation in ambient air = 93% - Number of days in need of supplemental oxygen d. Proportion of patients requiring invasive mechanical ventilation e. Proportion of patients having negative COVID-19 CRP at each visit f. Mean of serum cytokine levels: the panel of cytokines to quantify; IL1-??, IL1-ß, IL6, IL8, IL10, IL12, IL18, IL38, INF?, TNF??, CCL2, CCL3, CCL4, MIF and PAI-1 g. Incidence of adverse events related to medication and its administration h. Incidence in the appearance of serious bacterial, fungal or opportunistic infections i. Incidence of perforation of the gastrointestinal tract j. Leukocyte and neutrophil count mean k. Mean hemoglobin levels l. Platelet count mean m. Average levels of creatinemia n. Average bilirubin levels o. ALT and AST average levels;Timepoint(s) of evaluation of this end point: At day 28 or when the subject is discharged (whichever occurs first) | — |
Countries
Spain
Contacts
Public ContactAntonio Luque
Fundación para la Investigación Biomédica de Córdoba
Outcome results
None listed