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Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR)

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ClinicalTrials.gov Identifier: NCT04357860
Recruitment Status : Not yet recruiting
First Posted : April 22, 2020
Last Update Posted : April 27, 2020
Sponsor:
Collaborators:
Consejería de Salud y Familias - Junta de Andalucía
Red Andaluza de Ensayos Clínicos en Enfermedades Infecciosas (Red ANCRAID)
Information provided by (Responsible Party):
Maimónides Biomedical Research Institute of Córdoba

Tracking Information
First Submitted Date  ICMJE April 20, 2020
First Posted Date  ICMJE April 22, 2020
Last Update Posted Date April 27, 2020
Estimated Study Start Date  ICMJE April 27, 2020
Estimated Primary Completion Date July 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2020)
Ventilation requirements [ Time Frame: 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2020)
  • Crude mortality [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Crude mortality at 28 days
  • Time to clinical improvement [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Leukocyte and neutrophil count mean
  • Hemoglobin levels [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Mean hemoglobin levels
  • Platelet count [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Platelet count mean
  • Levels of creatinemia [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Average levels of creatinemia
  • Bilirubin levels [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Average bilirubin levels
  • ALT and AST levels [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    ALT and AST average levels
Original Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2020)
  • Crude mortality [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Crude mortality at 28 days
  • Time to clinical improvement [ Time Frame: 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 [ Time Frame: 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
  • Patients requiring invasive mechanical ventilation [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Proportion of patients requiring invasive mechanical ventilation
  • Patients having negative COVID-19 CRP at each visit [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Proportion of patients having negative COVID-19 CRP at each visit
  • Mean of serum cytokine levels [ Time Frame: 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 [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Incidence of adverse events related to medication and its administration
  • Appearance of serious bacterial, fungal or opportunistic infections [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Incidence in the appearance of serious bacterial, fungal or opportunistic infections
  • Perforation of the gastrointestinal tract [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Incidence of perforation of the gastrointestinal tract
  • Leukocyte and neutrophil count [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Leukocyte and neutrophil count mean
  • Hemoglobin levels [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Mean hemoglobin levels
  • Platelet count [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Platelet count mean
  • Levels of creatinemia [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Average levels of creatinemia
  • Bilirubin levels [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    Average bilirubin levels
  • ALT and AST levels [ Time Frame: At day 28 or when the subject is discharged (whichever occurs first) ]
    ALT and AST average levels
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Trial of Sarilumab in Adults With COVID-19
Official Title  ICMJE Clinical Trial of Sarilumab in Adults Hospitalized With COVID-19 Presenting Cytokine Release Syndrome
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • SARS-CoV 2
  • SARS
Intervention  ICMJE
  • Drug: Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA]
    Best available treatment up to 14 days plus Sarilumab 200 mg
  • Drug: Sarilumab 400 MG/2.28 ML Subcutaneous Solution [KEVZARA]
    Best available treatment up to 14 days plus Sarilumab 400 mg
  • Drug: Best available treatment
    Best available treatment up to 14 days
Study Arms  ICMJE
  • Experimental: Sarilumab 200 mg
    Subjects treated with the best available treatment up to 14 days plus Sarilumab 200 mg single dose.
    Intervention: Drug: Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA]
  • Experimental: Sarilumab 400 mg
    Subjects treated with the best available treatment up to 14 days plus Sarilumab 400 mg single dose.
    Intervention: Drug: Sarilumab 400 MG/2.28 ML Subcutaneous Solution [KEVZARA]
  • Active Comparator: Control
    Subjects treated with the best available treatment up to 14 days.
    Intervention: Drug: Best available treatment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 20, 2020)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 27, 2020
Estimated Primary Completion Date July 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Antonio Luque 0034671596070 uicec@imibic.org
Contact: José Carlos Garrido Gracia uicec@imibic.org
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04357860
Other Study ID Numbers  ICMJE SARICOR
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: All the information will be published and it will be available in open access.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: After the end of the trial.
Access Criteria: Contact uicec@imibic.org
Responsible Party Maimónides Biomedical Research Institute of Córdoba
Study Sponsor  ICMJE Maimónides Biomedical Research Institute of Córdoba
Collaborators  ICMJE
  • Consejería de Salud y Familias - Junta de Andalucía
  • Red Andaluza de Ensayos Clínicos en Enfermedades Infecciosas (Red ANCRAID)
Investigators  ICMJE
Study Director: Julián de la Torre Cisneros, MD Hospital Universitario Reina Sofía
PRS Account Maimónides Biomedical Research Institute of Córdoba
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP