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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

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.

Condition or disease Intervention/treatment Phase
Cytokine Storm COVID-19 Drug: Anakinra Drug: Normal saline Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
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
Official Title: Early Treatment of Cytokine Storm Syndrome in Covid-19
Actual Study Start Date : July 29, 2020
Estimated Primary Completion Date : January 2021
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 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.
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)

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.
Drug: Normal saline
The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
Other Name: NS




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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)

  3. 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

  4. 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.

  5. 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.

  6. 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.



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:

  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

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): NCT04362111


Contacts
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Contact: Walter W Chatham, MD 800-822-6478 wchatham@uabmc.edu
Contact: Angela Kendrach 205-996-5602 akendrach@uab.edu

Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Angelia Kendrach       akendrach@uabmc.edu   
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
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Principal Investigator: Walter W Chatham, MD University of Alabama at Birmingham
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Responsible Party: W Winn Chatham, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT04362111    
Other Study ID Numbers: Chatham-Cytokine Covid-19
First Posted: April 24, 2020    Key Record Dates
Last Update Posted: September 11, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: During study enrollment
Access Criteria: wchatham@uabmc.edu

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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
Additional relevant MeSH terms:
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Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents