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Early Treatment of Cytokine Storm Syndrome in Covid-19

Primary Purpose

Cytokine Storm, COVID-19

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Anakinra
Normal saline
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cytokine Storm

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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. 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

Sites / Locations

  • University of Alabama at Birmingham

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Anakinra Group

Control Group

Arm 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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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)
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
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.
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.
Absence of Supplemental Oxygen Requirement at Day 10
Percentage of participants able to maintain oxygen saturation >93% on room air by Day 10

Full Information

First Posted
April 21, 2020
Last Updated
August 1, 2023
Sponsor
University of Alabama at Birmingham
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1. Study Identification

Unique Protocol Identification Number
NCT04362111
Brief Title
Early Treatment of Cytokine Storm Syndrome in Covid-19
Official Title
Early Treatment of Cytokine Storm Syndrome in Covid-19
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
August 1, 2020 (Actual)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
June 1, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytokine Storm, COVID-19

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Two parallel treatment arms
Masking
ParticipantCare ProviderInvestigator
Masking Description
Investigator, care provider, and participant blinded
Allocation
Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Anakinra Group
Arm Type
Experimental
Arm 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.
Arm Title
Control Group
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Anakinra
Other Intervention Name(s)
recombinant human IL-ra (rhIL-1ra)
Intervention Description
The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
Intervention Type
Drug
Intervention Name(s)
Normal saline
Other Intervention Name(s)
NS
Intervention Description
The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
Primary Outcome Measure Information:
Title
Subjects Discharged From the Hospital Alive and Without the Need for Mechanical Ventilation.
Description
Percentage of subjects discharged from hospital alive and who did not require intubation and mechanical ventilation
Time Frame
Variable up to Day 28
Secondary Outcome Measure Information:
Title
Percentage of Subjects With 25% Change (Decrease) in Cytokine Storm Markers at 48-72 Hours After Dosing With Study Agent
Description
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
Title
Percentage of Subjects Without Increase in Oxygen Requirement and no Increase in Oxygen Delivery/Respiratory Support Measures After 48 Hours.
Description
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)
Title
Patients Requiring Minimal Oxygen Support at Day 10
Description
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
Title
Percentage of Subjects With Resolution of Laboratory Markers of Cytokine Storm Syndrome
Description
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
Title
Percentage of Subjects Who Develop Bacterial or Fungal or Non-Covid-19 Viral Infection
Description
Occurence of new bacterial or fungal or viral infection through the time of hospital discharge or Day 28.
Time Frame
Day 0-28
Title
Absence of Supplemental Oxygen Requirement at Day 10
Description
Percentage of participants able to maintain oxygen saturation >93% on room air by Day 10
Time Frame
0-10 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18 years old or older Molecular (pcRNA) diagnosis of SARS-CoV-2 infection Chest imaging studies consistent with Covid-19 pneumonia Hyperferritinemia (>700 ng/ml) History of fever >38 degrees C Any three of the following: Elevated d-dimer (> 500 ng/ml) thrombocytopenia (< 130,000/mm3) leucopenia (WBC <3500/mm3) or lymphopenia (<1000/mm3) elevated AST or ALT (> 2X ULN) elevated LDH (> 2X ULN) CRP > 100 mg/L Exclusion Criteria: Participation in other investigational treatment protocols for Covid-19 infection Culture confirmed active bacterial infection requiring antibiotic therapy On mechanical ventilation Previous known hypersensitivity reaction to anakinra Previous known hypersensitivity reaction to E Coli derived proteins Pregnant or breast-feeding females
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Walter W Chatham, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Contact PI by e-mail for protocol specifics Submission of results for peer reviewed publication
IPD Sharing Time Frame
During study enrollment
IPD Sharing Access Criteria
wchatham@uabmc.edu

Learn more about this trial

Early Treatment of Cytokine Storm Syndrome in Covid-19

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