Early Treatment of Cytokine Storm Syndrome in Covid-19

August 1, 2023 updated by: W Winn Chatham, University of Alabama at Birmingham
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.

Study Overview

Status

Completed

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.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anakinra Group
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 active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
Other Names:
  • recombinant human IL-ra (rhIL-1ra)
Placebo Comparator: Control Group
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.
The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
Other Names:
  • NS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjects Discharged From the Hospital Alive and Without the Need for Mechanical Ventilation.
Time Frame: Variable up to Day 28
Percentage of subjects discharged from hospital alive and who did not require intubation and mechanical ventilation
Variable up to Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Subjects With 25% Change (Decrease) in Cytokine Storm Markers at 48-72 Hours After Dosing With Study Agent
Time Frame: 48 hours after taking initial dose of anakinra/placebo
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
Percentage of Subjects Without Increase in Oxygen Requirement and no Increase in Oxygen Delivery/Respiratory Support Measures After 48 Hours.
Time Frame: Day 2 (48 hours)-Day 10 (240 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)
Patients Requiring Minimal Oxygen Support at Day 10
Time Frame: 0-10 days
Percentage of participants requiring no more than 2 L/min nasal canula oxygen to maintain oxygen saturation >93% by Day 10
0-10 days
Percentage of Subjects With Resolution of Laboratory Markers of Cytokine Storm Syndrome
Time Frame: Day 10
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
Percentage of Subjects Who Develop Bacterial or Fungal or Non-Covid-19 Viral Infection
Time Frame: Day 0-28
Occurence of new bacterial or fungal or viral infection through the time of hospital discharge or Day 28.
Day 0-28
Absence of Supplemental Oxygen Requirement at Day 10
Time Frame: 0-10 Days
Percentage of participants able to maintain oxygen saturation >93% on room air by Day 10
0-10 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Walter W Chatham, MD, University of Alabama at Birmingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2020

Primary Completion (Actual)

December 31, 2021

Study Completion (Actual)

June 1, 2023

Study Registration Dates

First Submitted

April 21, 2020

First Submitted That Met QC Criteria

April 23, 2020

First Posted (Actual)

April 24, 2020

Study Record Updates

Last Update Posted (Actual)

August 24, 2023

Last Update Submitted That Met QC Criteria

August 1, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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