Clinical Trial of Sarilumab in Adults With COVID-19
- Conditions
- SARS-CoV 2SARS
- Interventions
- Registration Number
- NCT04357860
- Lead Sponsor
- Maimónides Biomedical Research Institute of Córdoba
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 120
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sarilumab 400 mg Sarilumab 400 MG/2.28 ML Subcutaneous Solution [KEVZARA] Subjects treated with the best available treatment up to 14 days plus Sarilumab 400 mg single dose. Sarilumab 200 mg Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA] Subjects treated with the best available treatment up to 14 days plus Sarilumab 200 mg single dose. Control Best available treatment Subjects treated with the best available treatment up to 14 days.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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. - DeathProportion 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
Crude mortality At day 28 or when the subject is discharged (whichever occurs first) Crude mortality at 28 days
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 oxygenProportion 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
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
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
Trial Locations
- Locations (1)
Hospital Universitario Reina Sofía
🇪🇸Córdoba, Spain