Early Treatment of Cytokine Storm Syndrome in Covid-19

COVID-19 Clinical Trial

Official title:

Early Treatment of Cytokine Storm Syndrome in Covid-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04362111
• Other study ID #: Chatham-Cytokine Covid-19
• Status: Completed
• Phase: Phase 3
• Start date: August 1, 2020
• Est. completion date: June 1, 2023

Study information

• Verified date: August 2023
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 1, 2023
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Cytokine Release Syndrome
• Cytokine Storm

Intervention

Drug:
• Anakinra
The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
• Normal saline
The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Variable up to Day 28
Secondary	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.	48 hours after taking initial dose of anakinra/placebo
Secondary	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)	Day 2 (48 hours)-Day 10 (240 hours)
Secondary	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	0-10 days
Secondary	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.	Day 10
Secondary	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.	Day 0-28
Secondary	Absence of Supplemental Oxygen Requirement at Day 10	Percentage of participants able to maintain oxygen saturation >93% on room air by Day 10	0-10 Days