Early Treatment of Cytokine Storm Syndrome in Covid-19

The University of Alabama at Birmingham

Status and phase: Completed; Phase 3

Conditions: COVID-19; Cytokine Storm

Treatments: Drug: Anakinra; Drug: Normal saline

Study type: Interventional

Funder types: Other

Identifiers

NCT04362111

Chatham-Cytokine Covid-19

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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32 participants in 2 patient groups, including a placebo group

Anakinra Group

Experimental group

Description:

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.

Treatment:

Drug: Anakinra

Control Group

Placebo Comparator group

Description:

The control group will receive normal saline placebo subcutaneously every 6 hours for period of 10 days. For subjects meeting complete response criteria at 5 days, dosing will be decreased to twice daily for the remaining 5 days.

Treatment:

Drug: Normal saline