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Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to Covid-19 (ANA-COVID-GEAS) (ANA-COVID-GEAS)

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ClinicalTrials.gov Identifier: NCT04443881
Recruitment Status : Recruiting
First Posted : June 23, 2020
Last Update Posted : June 23, 2020
Sponsor:
Information provided by (Responsible Party):
Fundacion Miguel Servet

Brief Summary:
Phase 2/3 randomized, parallel group, 2-arm study (treatment vs. control), investigating the efficacy and safety of intravenous administration of anakinra, an interleukin 1 receptor antagonist ( IL-1), added to standard treatment, compared to standard treatment alone, to reduce hyperinflammation and respiratory distress in patients with SARS-CoV-2 infection.

Condition or disease Intervention/treatment Phase
COVID-19 Pnemonia Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret] Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A phase 2/3, randomized, open label, parallel group, 2-arm, multicenter study investigating the efficacy and safety of intravenous administrations of the study drug,
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to Covid-19. A Phase 2/3, Randomized, Open-label, Parallel Group, 2-arm, Multicenter Study Investigating the Efficacy and Safety of Intravenous Administrations of Anakinra, an Interleukin-1(IL-1) Receptor Antagonist, Added to Standard of Care, Versus Standard of Care, in Reducing Hyper-inflammation and Respiratory Distress in Patients With SARS- CoV-2 Infection
Actual Study Start Date : May 8, 2020
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Anakinra

Arm Intervention/treatment
Experimental: Anakinra Arm
Standard of care plus Anakinra (100mg) administered as 4-times daily i.v. infusions for a maximun of 15 days
Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]
Anakinra (100 mg/ 6 hours) i.v infusión during 15 days

No Intervention: Control Arm
Standard of care



Primary Outcome Measures :
  1. Treatment success, defined as number of patients not requiring mechanical ventilation to assess the effect of anakinra in addition to standard treatment on the need for mechanical ventilation in patients with severe COVID-19 and CSS pneumonia. [ Time Frame: Day 15 ]
    Treatment success, defined as number of patients not requiring mechanical ventilation by Day 15.

  2. Number of patients not requiring mechanical ventilation to assess the effect of anakinra in addition to standard treatment on the need for mechanical ventilation in patients with severe COVID-19 and CSS pneumonia. [ Time Frame: Day 28 ]
    Number of patients not requiring mechanical ventilation

  3. Time to mechanical ventilation to assess the effect of anakinra in addition to standard treatment on the need for mechanical ventilation in patients with severe COVID-19 and CSS pneumonia. [ Time Frame: Up to 28 days ]
    Time to mechanical ventilation

  4. Time to oxygen saturation normalization to assess the effect of anakinra in addition to standard treatment on the need for mechanical ventilation in patients with severe COVID-19 and CSS pneumonia. [ Time Frame: Up to 28 days ]
    Time to oxygen saturation normalization

  5. Stay in ICU and hospitalization to assess the effect of anakinra in addition to standard treatment on the need for mechanical ventilation in patients with severe COVID-19 and CSS pneumonia. [ Time Frame: Up to 28 days ]
    Stay in ICU and hospitalization


Secondary Outcome Measures :
  1. Total mortality rate to assess the effect of anakinra in addition to standard treatment on mortality in patients with severe COVID-19 and CSS pneumonia. [ Time Frame: day 28 ]
    Total mortality rate

  2. Mortality 48 hours, 7 days, in ICU and hospital to assess the effect of anakinra in addition to standard treatment on mortality in patients with severe COVID-19 and CSS pneumonia. [ Time Frame: 48 hours, 7 days ]
    Mortality 48 hours, 7 days, in ICU and hospital

  3. Viral clearance / viral shedding to assess the effect of anakinra in addition to standard treatment on mortality in patients with severe COVID-19 and CSS pneumonia. [ Time Frame: Up to 28 days ]
    Viral clearance / viral shedding

  4. To assess the effect of anakinra in addition to standard treatment on mortality in patients with severe COVID-19 and CSS pneumonia. [ Time Frame: At day 28 ]
    Frequency and severity of AEs: Treatment-emergent severe fatal and life-threatening serious adverse events (SAEs), Adverse events leading to premature discontinuation of study treatment, Anaphylactic/anaphylactoid reactions, Anakinra treatment group: Severe neutropenia, Treatment-emergent laboratory abnormalities.


Other Outcome Measures:
  1. Change in IL-6 to assess the effect of anakinra on IL-6, ferritin, and selected biomarkers relevant for hyperinflammation, MAS and cytokine storm change from baseline. [ Time Frame: During 28 days ]
    Change (improvement) in IL-6

  2. Change in ferritin to assess the effect of anakinra [ Time Frame: During 28 days ]
    Change (improvement) in ferritin

  3. Change in D-dimer to assess the effect of anakinra [ Time Frame: During 28 days ]
    Change (improvement) in D-dimer

  4. Change in TGs to assess the effect of anakinra [ Time Frame: During 28 days ]
    Change (improvement) in TGs

  5. Change in lymphopenia to assess the effect of anakinra [ Time Frame: During 28 days ]
    Change (improvement) in lymphopenia

  6. Change in CRP to assess the effect of anakinra [ Time Frame: During 28 days ]
    Change (improvement) in CRP

  7. Change in ESR to assess the effect of anakinra [ Time Frame: During 28 days ]
    Change (improvement) in ESR

  8. Change in LDH to assess the effect of anakinra [ Time Frame: During 28 days ]
    Change (improvement) in LDH

  9. Time to defervescence to assess the effect of anakinra [ Time Frame: During 28 days ]
    Time to defervescence (fever end)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • Inclusion Criteria:

    • Age 18-80 years.
    • Severe pneumonia COVID-19 defined as:
    • Nasopharyngeal smear with RCP positive for SARS-CoV-2
    • X-Rays (or other technique) pulmonary infiltrates compatible with pneumonia.
    • 1 or more of the following criteria:
    • Ambient air oxygen saturation <= 94% measured with a pulse oximeter.
    • Pa:FiO2 (partial pressure O2/fraction of inspired O2) <=300.
    • Sa:FiO2 (O2 saturation measured with pulse oximeter/ fraction of inspired O2) <=350.
    • High suspicion of CSS that could resemble MAS-like: represented by IL-6 values > 40 pg/mL and/or ferritin >500 ug/L and/or PCR > 30 mg/L (rationale: ≥ 5 upper normal limit) and/or LDH >300 UI/L. We have chosen these parameters because they are implemented in all the participating hospitals, they are a reflection of the cytokine storm and they have also been significant in terms of predicting mortality in patients with COVID-19 (9).
    • Written informed consent. The protocol will be explained to the patient in front of a nurse who will act as a legal witness by signing the document on behalf of the patient.
  • Exclusion Criteria:

    • Need for oro-tracheal intubation and/or invasive mechanical ventilation at the start of the study.
    • AST/ALT with values greater than 5 times normal levels.
    • Neutrophils < 1.500 cell/mmc.
    • Platelets < 50.000 cell/mmc.
    • Sepsis or pneumonia documented by other pathogens than SARS-CoV-2.
    • Existence of any life-threatening comorbidity or any other medical condition that, in the investigator's opinion, makes the patient unsuitable for inclusion.
    • Inability to obtain informed consent.
    • Positivity for HBV, HCV or tuberculin test serology.
    • Pregnancy.
    • Use of other previous or concomitant biological treatments. Patients in concomitant treatment with other biologicals that may interfere will be excluded: tocilizumab, canakinumab, TNFalfa inhibitors, JAKiinibs
    • Severe renal dysfunction (estimated glomerular filtration rate ≤ 30 ml / min / 1.73 m2) or receive continuous renal replacement therapy, hemodialysis or peritoneal dialysis.
    • Uncontrolled hypertension (sitting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg).
    • Administration of plasma from convalescent patients who have recovered from SARS-CoV-2 infection.
    • History of hypersensitivity or allergy to any component of the study drug.
    • Enrollment in another concurrent intervention clinical trial, or intake of an investigational medication within three months or 5 half-lives prior to inclusion in this study, if deemed to interfere with the objectives of this study as assessed by the investigator.
    • Predictable inability to cooperate with given instructions or study procedures.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04443881


Contacts
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Contact: Patricia Fanlo Mateo, PhD 848422163 patricia.fanlo.mateo@navarra.es
Contact: Ruth Garcia Rey 848422163 ruth.garcia.rey@navarra.es

Locations
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Spain
Hospital Clinic Recruiting
Barcelona, Cataluña, Spain
Contact: Sergio Prieto Gonzalez, PhD       SPRIETO@clinic.cat   
Hospital Universitario Vall d´Hebron Recruiting
Barcelona, Cataluña, Spain
Contact: Segundo Bujan Rivas, MD       bigarrenb@gmail.com   
Complexo Hospitalario Universitario de Santiago Recruiting
Santiago De Compostela, Galicia, Spain
Contact: Maria Carmen Freire Dapena, MD       mayka.freire@gmail.com   
Hospital Universitario Son Espases Recruiting
Palma De Mallorca, Mallorca, Spain
Contact: Lucio Pallarés Ferreres, MD         
Complejo Hospitalario de Navarra Recruiting
Pamplona, Navarra, Spain, 31008
Contact: Patricia Fanlo Mateo, PhD       patricia.fanlo.mateo@navarra.es   
Contact: Ruth García Rey    848422163    ruth.garcia.rey@navarra.es   
Hospital Universitario La Paz Recruiting
Madrid, Spain
Contact: Angel Robles Marhuenda, MD         
Principal Investigator: Francisco Arnalich Fernandez, MD         
Hospital Universitario Ramon y Cajal Recruiting
Madrid, Spain
Contact: Andres Gonzalez Garcia, Md       andres_gonzalez_garcia@hotmail.com   
Hospital Universitario y Politecnico La Fe Recruiting
Valencia, Spain
Contact: Jose Antonio Todoli Parra, MD       todoli75@gmail.com   
Complejo Hospitalario Universitario de Vigo Recruiting
Vigo, Spain
Contact: Ana Belen Argibay Filgueira, MD       anaargy@hotmail.com   
Hospital Clínico Universitario Lozano Blesa Recruiting
Zaragoza, Spain
Contact: Borja del Carmelo Gracia Tello, MD       gaunt_87@hotmail.com   
Sponsors and Collaborators
Fundacion Miguel Servet
Investigators
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Principal Investigator: Patricia Fanlo Mateo, PhD Complejo Hospitalario de Navarra
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Responsible Party: Fundacion Miguel Servet
ClinicalTrials.gov Identifier: NCT04443881    
Other Study ID Numbers: ANA-COVID-GEAS
First Posted: June 23, 2020    Key Record Dates
Last Update Posted: June 23, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: All collected IPD will be available for exploitation in future research projects. This statement also includes the availability of the study protocol, the statistical analysis plan, the informed consent form, the clinical study report and the analytic code.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Fundacion Miguel Servet:
Covid-19 disease
pneumonia
Cytokine Storm Sindrome
Anti IL-1
Anakinra
Additional relevant MeSH terms:
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Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents