Clinical Trial of Sarilumab in Adults With COVID-19

SARS-CoV 2 Clinical Trial

— SARICOR  

Official title:

Clinical Trial of Sarilumab in Adults Hospitalized With COVID-19 Presenting Cytokine Release Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04357860
• Other study ID #: SARICOR
• Status: Completed
• Phase: Phase 2
• Start date: April 28, 2020
• Est. completion date: April 6, 2021

Study information

• Verified date: April 2020
• Source: Maimónides Biomedical Research Institute of Córdoba
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: April 6, 2021
• Est. primary completion date: March 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• SARS
• SARS-CoV 2

Intervention

Drug:
• Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA]
Best available treatment up to 14 days plus Sarilumab 200 mg
• Sarilumab 400 MG/2.28 ML Subcutaneous Solution [KEVZARA]
Best available treatment up to 14 days plus Sarilumab 400 mg
• Best available treatment
Best available treatment up to 14 days

Locations

Country	Name	City	State
Spain	Hospital Universitario Reina Sofía	Córdoba

Sponsors (3)

Lead Sponsor	Collaborator
Maimónides Biomedical Research Institute of Córdoba	Consejería de Salud y Familias - Junta de Andalucía, Red Andaluza de Ensayos Clínicos en Enfermedades Infecciosas (Red ANCRAID)

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ventilation requirements	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	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Crude mortality	Crude mortality at 28 days	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Time to clinical improvement	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: - Not hospitalized with normal activity; - Not hospitalized but unable to have normal activity; - Hospitalized, without requiring oxygen supplementation; - Hospitalized, requiring oxygen supplementation; - Hospitalized, requiring ONAF, non-invasive mechanical ventilation or both; - Hospitalized requiring ECMO, invasive mechanical ventilation or both; - Death	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Time until improvement in oxygenation	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	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Proportion of patients requiring invasive mechanical ventilation	Proportion of patients requiring invasive mechanical ventilation in the trial	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Proportion of patients having negative COVID-19 CRP at each visit	Proportion of patients having negative COVID-19 CRP at each visit of the trial	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Mean of serum cytokine levels	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	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Adverse events related to medication and its administration	Incidence of adverse events related to medication and its administration	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Incidence in the appearance of serious bacterial, fungal or opportunistic infections	Incidence in the appearance of serious bacterial, fungal or opportunistic infections in the subjects	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Incidence of perforation of the gastrointestinal tract	Incidence of perforation of the gastrointestinal tract in subjects	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Leukocyte and neutrophil count	Leukocyte and neutrophil count mean	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Hemoglobin levels	Mean hemoglobin levels	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Platelet count	Platelet count mean	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Levels of creatinemia	Average levels of creatinemia	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	Bilirubin levels	Average bilirubin levels	At day 28 or when the subject is discharged (whichever occurs first)
Secondary	ALT and AST levels	ALT and AST average levels	At day 28 or when the subject is discharged (whichever occurs first)