SARS, SARS-CoV 2
Conditions
Brief summary
Early administration of sarilumab in hospitalized patients infected with COVID-19 who have pulmonary infiltrates and are at high risk of unfavorable evolution could decrease/prevent progression to acute respiratory distress syndrome (ARDS) requiring high flow nasal oxygenation (HFNO) or either invasive or non-invasive mechanical ventilation.
Interventions
Best available treatment up to 14 days plus Sarilumab 200 mg
DRUGSarilumab 400 MG/2.28 ML Subcutaneous Solution [KEVZARA]
Best available treatment up to 14 days plus Sarilumab 400 mg
Best available treatment up to 14 days
Sponsors
Junta de Andalucia
Red Andaluza de Ensayos Clínicos en Enfermedades Infecciosas (Red ANCRAID)
Maimónides Biomedical Research Institute of Córdoba
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years and \<75 years * Admission for confirmed respiratory symptoms to COVID-19 based on a positive PCR in a sample of the respiratory tract in the local laboratory in the absence of respiratory distress syndrome requiring ONAF or mechanical ventilation * Interstitial pneumonia confirmed by chest radiography or CT * IL-6 levels\> 40 pg / ml. In its absence, D-Dimer (DD)\> 1500 or\> 1000 may be included if progressive increases are documented * Negative pregnancy test in women of childbearing age * Signature of informed consent
Exclusion criteria
* SOFA score\> 6 points * Patient who, in the researcher's opinion, is not a subsidiary of invasive mechanical ventilation * Neutrophil count \<2 x 103 / μL * Platelet count \<100 x 103 / μL * ALT or AST levels\> 5 times the upper limit of normal * Severe renal failure (CrCr \<30 ml / min) * Active bacterial infectious process * Active tuberculosis, history of not completing treatment against tuberculosis, suspicion of extrapulmonary tuberculosis * History of intestinal ulcer or diverticulitis * History of hypersensitivity reactions to Sarilumab or its excipients * Treatment with TNF antagonists * Previous treatment with anti-IL6 in the previous 30 days * 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 * Concomitant treatment with immunomodulators, among which are Vitamin D or statins. Macrolides such as azithromycin are acceptable * Patients on immunosuppressive treatment for any cause * HIV-infected patients with CD4 \<200 / mm3 * Past or current history of autoimmune disease or systemic inflammatory disease * Patients who have received or are planning therapy with immunomodulatory antibodies, including immunoglobulins * 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 * Pregnancy * Any other condition that, in clinical judgment, prevents adherence to the patient's protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventilation requirements | At day 28 or when the subject is discharged (whichever occurs first) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to clinical improvement | At day 28 or when the subject is discharged (whichever occurs first) | 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 |
| Time until improvement in oxygenation | At day 28 or when the subject is discharged (whichever occurs first) | 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 |
| Proportion of patients requiring invasive mechanical ventilation | At day 28 or when the subject is discharged (whichever occurs first) | Proportion of patients requiring invasive mechanical ventilation in the trial |
| Proportion of patients having negative COVID-19 CRP at each visit | At day 28 or when the subject is discharged (whichever occurs first) | Proportion of patients having negative COVID-19 CRP at each visit of the trial |
| Mean of serum cytokine levels | At day 28 or when the subject is discharged (whichever occurs first) | Mean of serum cytokine levels: the panel of cytokines to quantify; IL1-��, IL1-β, IL6, IL8, IL10, IL12, IL18, IL38, INFɣ, TNF��, CCL2, CCL3, CCL4, MIF and PAI-1 |
| Adverse events related to medication and its administration | At day 28 or when the subject is discharged (whichever occurs first) | Incidence of adverse events related to medication and its administration |
| Incidence in the appearance of serious bacterial, fungal or opportunistic infections | At day 28 or when the subject is discharged (whichever occurs first) | Incidence in the appearance of serious bacterial, fungal or opportunistic infections in the subjects |
| Crude mortality | At day 28 or when the subject is discharged (whichever occurs first) | Crude mortality at 28 days |
| Leukocyte and neutrophil count | At day 28 or when the subject is discharged (whichever occurs first) | Leukocyte and neutrophil count mean |
| Hemoglobin levels | At day 28 or when the subject is discharged (whichever occurs first) | Mean hemoglobin levels |
| Platelet count | At day 28 or when the subject is discharged (whichever occurs first) | Platelet count mean |
| Levels of creatinemia | At day 28 or when the subject is discharged (whichever occurs first) | Average levels of creatinemia |
| Bilirubin levels | At day 28 or when the subject is discharged (whichever occurs first) | Average bilirubin levels |
| ALT and AST levels | At day 28 or when the subject is discharged (whichever occurs first) | ALT and AST average levels |
| Incidence of perforation of the gastrointestinal tract | At day 28 or when the subject is discharged (whichever occurs first) | Incidence of perforation of the gastrointestinal tract in subjects |
Countries
Spain
Outcome results
None listed