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Early Treatment of Cytokine Storm Syndrome in Covid-19

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ClinicalTrials.gov Identifier: NCT04362111
Recruitment Status : Recruiting
First Posted : April 24, 2020
Last Update Posted : September 11, 2020
Sponsor:
Information provided by (Responsible Party):
W Winn Chatham, University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE April 21, 2020
First Posted Date  ICMJE April 24, 2020
Last Update Posted Date September 11, 2020
Actual Study Start Date  ICMJE July 29, 2020
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 8, 2020)
Percentage of patients discharged from the hospital alive and without the need for mechanical ventilation. [ Time Frame: Variable up to Day 28 ]
Percentage of subjects discharged from hospital without the need for intubation and mechanical ventilation
Original Primary Outcome Measures  ICMJE
 (submitted: April 23, 2020)
No increase in oxygen requirement and no increase in respiratory support measures [ Time Frame: 48 hours ]
Supplemental oxygen requirement to maintain oxygen saturation >90% stable or decreased without escalation of respiratory measures (addition of CPAP, initiation of mechanical ventilation)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2020)
  • Percentage of subjects with 25% change (decrease) in cytokine storm markers at 48 hours [ Time Frame: 48 hours ]
    25% change (decrease) in noted baseline elevations of serum ferritin, LDH, CRP, and d-dimer.
  • Percentage of subjects without increase in oxygen requirement and no increase in oxygen delivery/respiratory support measures after 48 hours. [ Time Frame: Day 2 (48 hours)-Day 10 (240 hours) ]
    Supplemental oxygen requirement to maintain oxygen saturation >90% stable or decreased without escalation of respiratory support measures (addition of CPAP, initiation of mechanical ventilation)
  • Average time in days to achieve sustained ≥93% oxygen saturation without oxygen/respiratory support [ Time Frame: 0-10 days ]
    Time from initial dosing of IP to achievement of ≥93% oxygen saturation on room air for 24 hours
  • Percentage of subjects with resolution of laboratory markers of Cytokine Storm syndrome [ Time Frame: Day 10 ]
    Normalization or ≥ 75% improvement by Day 10 (120 hours) in each of the following laboratory CSS attributes elevated beyond the normal range at randomization: ferritin, fibrinogen, AST, ALT, leucopenia, thrombocytopenia, d-dimer, CRP, triglycerides, sCD25.
  • Percentage of subjects who develop bacterial or fungal or non-Covid-19 viral infection [ Time Frame: Day 0-28 ]
    No increased prevalence of bacterial or fungal or viral infection through the time of hospital discharge until Day 28.
  • Percentage of subjects who develop neutralizing antibody to Covid-19 [ Time Frame: Day 28 ]
    No failure to develop neutralizing antibody to Covid-19 measured at Day 28.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2020)
  • Improvement in Cytokine Storm markers [ Time Frame: 72 hours ]
    25% decrease in noted baseline elevations of serum ferritin, LDH, CRP, and d-dimer.
  • No requirement for mechanical ventilation [ Time Frame: Day 5 (120 hours) ]
    Subjects discharged from hospital without the need for mechanical ventilation
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Early Treatment of Cytokine Storm Syndrome in Covid-19
Official Title  ICMJE Early Treatment of Cytokine Storm Syndrome in Covid-19
Brief Summary This proposal addresses the problem of preventing the very high mortality and morbidity associated with the development of Cytokine Storm Syndrome (CSS) associated respiratory failure in Covid-19 infection.
Detailed Description The first aim of this project is to determine whether rapidly assayed early clinical laboratory markers of CSS (eCSS: leucopenia, lymphopenia, and elevated ferritin, d-dimer, LDH, CRP, and AST/ALT) in patients admitted to the hospital with respiratory compromise in the setting of Covid-19 infection can accurately identify patients with CSS as defined by validated CSS case definitions (H-Score, aHLH-2004). Confirmation of eCSS predictive of evolving CSS will identify patients at risk for rapid deterioration of lung function and inform early initiation of treatment for CSS. Genotyping studies will also be performed on patients with confirmed CSS to determine whether perforin pathway mutations commonly present in CSS associated with other disorders are present. The second aim is to determine whether early treatment with rhIL-1Ra (anakinra) in patients admitted to the hospital with markers of CSS improves or prevents deterioration of respiratory dysfunction and prevents the development of respiratory failure requiring mechanical ventilation.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Two parallel treatment arms
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Investigator, care provider, and participant blinded
Primary Purpose: Treatment
Condition  ICMJE
  • Cytokine Storm
  • COVID-19
Intervention  ICMJE
  • Drug: Anakinra
    The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
    Other Name: recombinant human IL-ra (rhIL-1ra)
  • Drug: Normal saline
    The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
    Other Name: NS
Study Arms  ICMJE
  • Experimental: Anakinra Group
    The active treatment group will receive anakinra 100 mg subcutaneously every 6 hours for period of 10 days. For subjects meeting complete response criteria at 5 days, dosing will be decreased to 100 mg twice daily for the remaining 5 days.
    Intervention: Drug: Anakinra
  • Placebo Comparator: Control Group
    The control group will receive normal saline placebo subcutaneously every 6 hours for period of 10 days. For subjects meeting complete repsonse criteria at 5 days, dosing wll be decreased to twice daily for the remaining 5 days.
    Intervention: Drug: Normal saline
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 8, 2020)
30
Original Estimated Enrollment  ICMJE
 (submitted: April 23, 2020)
20
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 18 years old or older
  2. Molecular (pcRNA) diagnosis of SARS-CoV-2 infection
  3. Chest imaging studies consistent with Covid-19 pneumonia
  4. Hyperferritinemia (>700 ng/ml)
  5. Fever >38 degrees C
  6. Any three of the following:

    1. Elevated d-dimer (> 500 ng/ml)
    2. thrombocytopenia (< 130,000/mm3)
    3. leucopenia (WBC <3500/mm3) or lymphopenia (<1000/mm3)
    4. elevated AST or ALT (> 2X ULN)
    5. elevated LDH (> 2X ULN)
    6. CRP > 100 mg/L

Exclusion Criteria:

  1. Participation in other investigational treatment protocols for Covid-19 infection
  2. Culture confirmed active bacterial infection requiring antibiotic therapy
  3. On mechanical ventilation
  4. Previous known hypersensitivity reaction to anakinra
  5. Previous known hypersensitivity reaction to E Coli derived proteins
  6. Pregnant or breast-feeding females
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Walter W Chatham, MD 800-822-6478 wchatham@uabmc.edu
Contact: Angela Kendrach 205-996-5602 akendrach@uab.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04362111
Other Study ID Numbers  ICMJE Chatham-Cytokine Covid-19
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Contact PI by e-mail for protocol specifics Submission of results for peer reviewed publication
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: During study enrollment
Access Criteria: wchatham@uabmc.edu
Responsible Party W Winn Chatham, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Walter W Chatham, MD University of Alabama at Birmingham
PRS Account University of Alabama at Birmingham
Verification Date September 2020

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