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.
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
32
The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
University of Alabama at Birmingham
Birmingham, Alabama, United States
Subjects Discharged From the Hospital Alive and Without the Need for Mechanical Ventilation.
Percentage of subjects discharged from hospital alive and who did not require intubation and mechanical ventilation
Time frame: Variable up to Day 28
Percentage of Subjects With 25% Change (Decrease) in Cytokine Storm Markers at 48-72 Hours After Dosing With Study Agent
25% change (decrease) in noted baseline elevations of serum ferritin and CRP measured 48-72 hours after following initial dosing of anakinra/placebo.
Time frame: 48 hours after taking initial dose of anakinra/placebo
Percentage of Subjects Without Increase in Oxygen Requirement and no Increase in Oxygen Delivery/Respiratory Support Measures After 48 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)
Time frame: Day 2 (48 hours)-Day 10 (240 hours)
Patients Requiring Minimal Oxygen Support at Day 10
Percentage of participants requiring no more than 2 L/min nasal canula oxygen to maintain oxygen saturation \>93% by Day 10
Time frame: 0-10 days
Percentage of Subjects With Resolution of Laboratory Markers of Cytokine Storm Syndrome
Normalization or ≥ 75% improvement by Day 10 (120 hours) in each (all) of the following laboratory CSS attributes elevated beyond the normal range at randomization: ferritin, d-dimer, CRP, and LDH.
Time frame: Day 10
Percentage of Subjects Who Develop Bacterial or Fungal or Non-Covid-19 Viral Infection
Occurence of new bacterial or fungal or viral infection through the time of hospital discharge or Day 28.
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Time frame: Day 0-28
Absence of Supplemental Oxygen Requirement at Day 10
Percentage of participants able to maintain oxygen saturation \>93% on room air by Day 10
Time frame: 0-10 Days