Cytokine StormPhase 3NCT04362111
Early Treatment of Cytokine Storm Syndrome in Covid-19
A Phase 3 study testing Anakinra and Normal saline in people with Cytokine Storm and COVID-19, run by University of Alabama at Birmingham at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cytokine Storm, COVID-19
- What is being tested?
- Anakinra and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2020to 1 Jun 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 12Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
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.
Read the 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.
- Conditions
- Cytokine Storm, COVID-19
- Being tested
- Anakinra, Normal saline
- Medical subject headings
- Cytokine Release Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnakinraDrug
Also called recombinant human IL-ra (rhIL-1ra)
The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
Normal salineDrug
Also called NS
The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
| Study group | Role | What they receive |
|---|---|---|
| Anakinra Group | Experimental | 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. Receives: Drug: Anakinra |
| Control Group | Placebo comparator | 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. Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Variable up to Day 28
Secondary outcomes (6)
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.
Measured: 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.
Supplemental oxygen requirement to maintain oxygen saturation >90% stable or decreased without escalation of respiratory support measures (addition of CPAP, initiation of mechanical ventilation)
Measured: Day 2 (48 hours)-Day 10 (240 hours)
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
Measured: 0-10 days
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.
Measured: Day 10
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.
Measured: Day 0-28
Absence of Supplemental Oxygen Requirement at Day 10
Percentage of participants able to maintain oxygen saturation >93% on room air by Day 10
Measured: 0-10 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start1 Aug 2020
- Primary completion31 Dec 2021
- Study completion1 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cytokine StormStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two parallel treatment arms
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, W Winn Chatham, University of Alabama at Birmingham
- Investigators
- Walter W Chatham, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04362111
- Sponsor's protocol ID
- Chatham-Cytokine Covid-19
- Status last verified
- Aug 2023
- First submitted
- 21 Apr 2020
- Last updated
- 24 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Contact PI by e-mail for protocol specifics Submission of results for peer reviewed publication
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Treatment of Cytokine Storm Syndrome in Covid-19
- ClinicalTrials.gov ID
- NCT04362111
- Acronym / sponsor ID
- Chatham-Cytokine Covid-19
- Conditions
- Cytokine Storm, COVID-19
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 1 Aug 2020 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 1 Jun 2023 (actual)
- First posted
- 24 Apr 2020 (actual)
- Results
- Posted 24 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Two parallel treatment arms
| Arm | Type | Receives |
|---|---|---|
| Anakinra Group | Experimental | Drug: AnakinraThe 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. |
| Control Group | Placebo comparator | Drug: Normal salineThe 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnakinraAlso: recombinant human IL-ra (rhIL-1ra)The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days | Drug | Anakinra Group |
| Normal salineAlso: NSThe control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days | Drug | Control Group |
Primary outcome
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
6 secondary outcomes
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
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)
Patients Requiring Minimal Oxygen Support at Day 10
Time frame: 0-10 days
Percentage of Subjects With Resolution of Laboratory Markers of Cytokine Storm Syndrome
Time frame: Day 10
Percentage of Subjects Who Develop Bacterial or Fungal or Non-Covid-19 Viral Infection
Time frame: Day 0-28
Absence of Supplemental Oxygen Requirement at Day 10
Time frame: 0-10 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Contact PI by e-mail for protocol specifics Submission of results for peer reviewed publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Walter W Chatham, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Anakinra and Normal saline in people with Cytokine Storm and COVID-19, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Subjects Discharged From the Hospital Alive and Without the Need for Mechanical Ventilation. (time frame: Variable up to Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2023.