Clinical trial NCT04362111: Early Treatment of Cytokine Storm Syndrome in Covid-19
Official title: Early Treatment of Cytokine Storm Syndrome in Covid-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cytokine Storm
COVID-19
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two parallel treatment arms
Primary purpose: TREATMENT

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.

Eligibility 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. History of 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

Primary outcomes:
measure: Subjects Discharged From the Hospital Alive and Without the Need for Mechanical Ventilation.
timeFrame: Variable up to Day 28
Secondary outcomes:
measure: Percentage of Subjects With 25% Change (Decrease) in Cytokine Storm Markers at 48-72 Hours After Dosing With Study Agent
timeFrame: 48 hours after taking initial dose of anakinra/placebo
measure: Percentage of Subjects Without Increase in Oxygen Requirement and no Increase in Oxygen Delivery/Respiratory Support Measures After 48 Hours.
timeFrame: Day 2 (48 hours)-Day 10 (240 hours)
measure: Patients Requiring Minimal Oxygen Support at Day 10
timeFrame: 0-10 days
measure: Percentage of Subjects With Resolution of Laboratory Markers of Cytokine Storm Syndrome
timeFrame: Day 10
measure: Percentage of Subjects Who Develop Bacterial or Fungal or Non-Covid-19 Viral Infection
timeFrame: Day 0-28
measure: Absence of Supplemental Oxygen Requirement at Day 10
timeFrame: 0-10 Days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Walter W Chatham, MD
role: PRINCIPAL_INVESTIGATOR
References: