Clinical trial NCT04357860: Clinical Trial of Sarilumab in Adults With COVID-19
Official title: Clinical Trial of Sarilumab in Adults Hospitalized With COVID-19 Presenting Cytokine Release Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: SARS-CoV 2
SARS
Lead sponsor: Maimónides Biomedical Research Institute of Córdoba
Sponsor class: OTHER
Collaborators: name: Junta de Andalucia
name: Red Andaluza de Ensayos Clínicos en Enfermedades Infecciosas (Red ANCRAID)
First posted: 2020-04-22
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Ventilation requirements
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
Secondary outcomes:
measure: Crude mortality
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Time to clinical improvement
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Time until improvement in oxygenation
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Proportion of patients requiring invasive mechanical ventilation
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Proportion of patients having negative COVID-19 CRP at each visit
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Mean of serum cytokine levels
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Adverse events related to medication and its administration
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Incidence in the appearance of serious bacterial, fungal or opportunistic infections
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Incidence of perforation of the gastrointestinal tract
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Leukocyte and neutrophil count
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Hemoglobin levels
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Platelet count
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Levels of creatinemia
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: Bilirubin levels
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
measure: ALT and AST levels
timeFrame: At day 28 or when the subject is discharged (whichever occurs first)
Other outcomes:
Locations:
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
Study officials:
affiliation: Hospital Universitario Reina Sofía
name: Julián de la Torre Cisneros, MD
role: STUDY_DIRECTOR
References:
citation: Merchante N, Carcel S, Garrido-Gracia JC, Trigo-Rodriguez M, Moreno MAE, Leon-Lopez R, Espindola-Gomez R, Alonso EA, Garcia DV, Romero-Palacios A, Perez-Camacho I, Gutierrez-Gutierrez B, Martinez-Marcos FJ, Fernandez-Roldan C, Perez-Crespo PMM, Cano AA, Leon E, Corzo JE, de la Fuente C, Torre-Cisneros J. Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial. Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0210721. doi: 10.1128/AAC.02107-21. Epub 2021 Dec 13.
citation: Leon Lopez R, Fernandez SC, Limia Perez L, Romero Palacios A, Fernandez-Roldan MC, Aguilar Alonso E, Perez Camacho I, Rodriguez-Bano J, Merchante N, Olalla J, Esteban-Moreno MA, Santos M, Luque-Pineda A, Torre-Cisneros J. Efficacy and safety of early treatment with sarilumab in hospitalised adults with COVID-19 presenting cytokine release syndrome (SARICOR STUDY): protocol of a phase II, open-label, randomised, multicentre, controlled clinical trial. BMJ Open. 2020 Nov 14;10(11):e039951. doi: 10.1136/bmjopen-2020-039951.