Trial Outcomes & Findings for Early Treatment of Cytokine Storm Syndrome in Covid-19 (NCT NCT04362111)
NCT ID: NCT04362111
Last Updated: 2023-08-24
Results Overview
Percentage of subjects discharged from hospital alive and who did not require intubation and mechanical ventilation
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
32 participants
Primary outcome timeframe
Variable up to Day 28
Results posted on
2023-08-24
Participant Flow
Subjects for enrollment were identified by pre-screening all patients admitted to the University of Alabama Hospital for treatment of Covid-19 pneumonia from August 1, 2020-January 15, 2021. Patients who were admitted with a new requirement for supplemental oxygen to maintain arterial oxygen saturation \>93% but not yet requiring mechanical ventilation and who had admission laboratory studies meeting study inclusion criteria for evidence of inflammation were approached for enrollment.
Patients who met inclusion/exclusion criteria and who had ongoing or increasing oxygen requirement were consented and enrolled. Once consented and enrolled, all subjects were randomly assigned to the two treatment groups. No participants were excluded after enrollment and randomization. Two subjects withdrew consent within 48 hours of enrollment.
Participant milestones
| Measure |
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.
Anakinra: The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
|
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.
Normal saline: The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
17
|
|
Overall Study
COMPLETED
|
15
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Early Treatment of Cytokine Storm Syndrome in Covid-19
Baseline characteristics by cohort
| Measure |
Anakinra Group
n=15 Participants
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.
Anakinra: The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
|
Control Group
n=15 Participants
The control group will receive normal saline placebo subcutaneously every 6 hours for period of 10 days. For subjects meeting complete repsonse criteria at 5 days, dosing wll be decreased to twice daily for the remaining 5 days.
Normal saline: The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.2 years
STANDARD_DEVIATION 8.2 • n=99 Participants
|
61.8 years
STANDARD_DEVIATION 12.2 • n=107 Participants
|
63.0 years
STANDARD_DEVIATION 10.2 • n=206 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Co-morbidities
Cardiovascular Disease
|
4 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Co-morbidities
Diabetes
|
5 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Co-morbidities
Hypertension
|
11 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
21 Participants
n=206 Participants
|
|
Number of Participants that Smoke
|
6 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Variable up to Day 28Percentage of subjects discharged from hospital alive and who did not require intubation and mechanical ventilation
Outcome measures
| Measure |
Anakinra Group
n=15 Participants
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.
Anakinra: The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
|
Control Group
n=15 Participants
The control group will receive normal saline placebo subcutaneously every 6 hours for period of 10 days. For subjects meeting complete repsonse criteria at 5 days, dosing wll be decreased to twice daily for the remaining 5 days.
Normal saline: The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
|
|---|---|---|
|
Subjects Discharged From the Hospital Alive and Without the Need for Mechanical Ventilation.
|
10 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: 48 hours after taking initial dose of anakinra/placebo25% change (decrease) in noted baseline elevations of serum ferritin and CRP measured 48-72 hours after following initial dosing of anakinra/placebo.
Outcome measures
| Measure |
Anakinra Group
n=15 Participants
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.
Anakinra: The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
|
Control Group
n=15 Participants
The control group will receive normal saline placebo subcutaneously every 6 hours for period of 10 days. For subjects meeting complete repsonse criteria at 5 days, dosing wll be decreased to twice daily for the remaining 5 days.
Normal saline: The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
|
|---|---|---|
|
Percentage of Subjects With 25% Change (Decrease) in Cytokine Storm Markers at 48-72 Hours After Dosing With Study Agent
|
6 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: 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)
Outcome measures
| Measure |
Anakinra Group
n=15 Participants
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.
Anakinra: The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
|
Control Group
n=15 Participants
The control group will receive normal saline placebo subcutaneously every 6 hours for period of 10 days. For subjects meeting complete repsonse criteria at 5 days, dosing wll be decreased to twice daily for the remaining 5 days.
Normal saline: The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
|
|---|---|---|
|
Percentage of Subjects Without Increase in Oxygen Requirement and no Increase in Oxygen Delivery/Respiratory Support Measures After 48 Hours.
|
8 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: 0-10 daysPercentage of participants requiring no more than 2 L/min nasal canula oxygen to maintain oxygen saturation \>93% by Day 10
Outcome measures
| Measure |
Anakinra Group
n=15 Participants
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.
Anakinra: The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
|
Control Group
n=15 Participants
The control group will receive normal saline placebo subcutaneously every 6 hours for period of 10 days. For subjects meeting complete repsonse criteria at 5 days, dosing wll be decreased to twice daily for the remaining 5 days.
Normal saline: The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
|
|---|---|---|
|
Patients Requiring Minimal Oxygen Support at Day 10
|
8 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: Day 10Normalization 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.
Outcome measures
| Measure |
Anakinra Group
n=15 Participants
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.
Anakinra: The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
|
Control Group
n=15 Participants
The control group will receive normal saline placebo subcutaneously every 6 hours for period of 10 days. For subjects meeting complete repsonse criteria at 5 days, dosing wll be decreased to twice daily for the remaining 5 days.
Normal saline: The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
|
|---|---|---|
|
Percentage of Subjects With Resolution of Laboratory Markers of Cytokine Storm Syndrome
|
0 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Day 0-28Occurence of new bacterial or fungal or viral infection through the time of hospital discharge or Day 28.
Outcome measures
| Measure |
Anakinra Group
n=15 Participants
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.
Anakinra: The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
|
Control Group
n=15 Participants
The control group will receive normal saline placebo subcutaneously every 6 hours for period of 10 days. For subjects meeting complete repsonse criteria at 5 days, dosing wll be decreased to twice daily for the remaining 5 days.
Normal saline: The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
|
|---|---|---|
|
Percentage of Subjects Who Develop Bacterial or Fungal or Non-Covid-19 Viral Infection
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 0-10 DaysPercentage of participants able to maintain oxygen saturation \>93% on room air by Day 10
Outcome measures
| Measure |
Anakinra Group
n=15 Participants
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.
Anakinra: The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
|
Control Group
n=15 Participants
The control group will receive normal saline placebo subcutaneously every 6 hours for period of 10 days. For subjects meeting complete repsonse criteria at 5 days, dosing wll be decreased to twice daily for the remaining 5 days.
Normal saline: The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
|
|---|---|---|
|
Absence of Supplemental Oxygen Requirement at Day 10
|
4 Participants
|
9 Participants
|
Adverse Events
Anakinra Group
Serious events: 9 serious events
Other events: 14 other events
Deaths: 4 deaths
Control Group
Serious events: 7 serious events
Other events: 13 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
Anakinra Group
n=15 participants at risk
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.
Anakinra: The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
|
Control Group
n=15 participants at risk
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.
Normal saline: The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome
|
60.0%
9/15 • Number of events 9 • 60 days
|
46.7%
7/15 • Number of events 9 • 60 days
|
|
Vascular disorders
Arterial ischemia
|
26.7%
4/15 • Number of events 4 • 60 days
|
33.3%
5/15 • Number of events 5 • 60 days
|
Other adverse events
| Measure |
Anakinra Group
n=15 participants at risk
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.
Anakinra: The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
|
Control Group
n=15 participants at risk
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.
Normal saline: The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
|
|---|---|---|
|
Blood and lymphatic system disorders
Venous thrombosis
|
26.7%
4/15 • Number of events 4 • 60 days
|
20.0%
3/15 • Number of events 3 • 60 days
|
|
Renal and urinary disorders
Acute Renal Failure
|
46.7%
7/15 • Number of events 7 • 60 days
|
40.0%
6/15 • Number of events 6 • 60 days
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.7%
1/15 • Number of events 1 • 60 days
|
0.00%
0/15 • 60 days
|
|
Blood and lymphatic system disorders
Anemia
|
93.3%
14/15 • Number of events 14 • 60 days
|
86.7%
13/15 • Number of events 13 • 60 days
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
33.3%
5/15 • Number of events 5 • 60 days
|
33.3%
5/15 • Number of events 5 • 60 days
|
|
Gastrointestinal disorders
Gastrointestinal bleeding
|
6.7%
1/15 • Number of events 1 • 60 days
|
0.00%
0/15 • 60 days
|
Additional Information
Walter Winn Chatham MD
University of Alabama at Birmingham
Phone: 205-612-7402
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place