Heart Failure
Conditions
Brief summary
Anakinra ADHF is a double-blind randomized clinical trial of anakinra, recombinant human interleukin-1 receptor blocker, or placebo in patients with acute decompensated heart failure with the aim to quench the acute inflammatory response, as measured by the area-under-the-curve for C reactive protein over 14 days.
Interventions
DRUGAnakinra (high dose)
Anakinra 100 mg daily twice daily for days 1, 2, and 3
DRUGAnakinra (standard dose)
Anakinra 100 mg daily for days 4-14
DRUGPlacebo
Placebo twice daily for days 1, 2, and 3
Sponsors
American Heart Association
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
All 5 criteria need to be met for enrollment of the patient in the study 1. Primary diagnosis of acute decompensated heart failure within the last 24 hours as evidenced by both of the following: 1. dyspnea or respiratory distress or tachypnea at rest or with minimal exertion 2. evidence of elevated cardiac filling pressure or pulmonary congestion (at least one of the conditions must be met); i. pulmonary congestion/edema at physical exam OR chest x-ray; ii. plasma Brain Natriuretic Peptide (BNP) levels ≥200 pg/mL; iii.invasive measurement of left ventricular end-diastolic pressure \>18 mmHg or of pulmonary artery occluding pressure (wedge) \>16 mmHg. 2. Left ventricular systolic dysfunction (LVEF\<40%) during index hospitalization or prior 12 months. 3. Age ≥18 years old 4. Willing and able to provide written informed consent. 5. Screening plasma C-reactive protein levels \>5 mg/L.
Exclusion criteria
Subjects will not be eligible if they meet any of the following 15
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C Reactive Protein | 3 days | The proportional area-under-the-curve for plasma C reactive protein (CRP) levels measured during the first 3 days of admission. The proportion (y-axis) is calculated at each time-point with respect to the baseline CRP. The resultant y-axis is a unitless proportion. The x-axis is listed as days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Ejection Fraction | 14 days | Change in left ventricular ejection fraction (LVEF) between admission and 14 day follow up. This value is expressed as absolute change in measured LVEF. For example, if baseline LVEF = 20% and 14 day LVEF = 25%, this would be reported as an absolute change of 5%. |
| Brachial Artery Vasoreactivity | 14 days | Change in flow mediated vasodilatation (FMD) of the brachial artery. Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter. The change is FMD is reported as the % change in FMD from baseline to 14 days. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anakinra (Short) Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14
Anakinra (high dose): Anakinra 100 mg daily twice daily for days 1, 2, and 3
Anakinra (standard dose): Anakinra 100 mg daily for days 4-14 | 15 |
| Placebo Placebo injections twice daily for the first 3 days then once daily for days 4-14.
Placebo: Placebo twice daily for days 1, 2, and 3
Placebo: Placebo daily for days 4-14 | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Total | Anakinra (Short) | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 13 Participants | 13 Participants |
| Age, Continuous | 58 years | 60 years | 54 years |
| C-reactive protein | 23.8 mg/L | 22.3 mg/L | 27.4 mg/L |
| Region of Enrollment United States | 30 participants | 15 participants | 15 participants |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 21 Participants | 9 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 15 | 6 / 15 |
| serious Total, serious adverse events | 2 / 15 | 4 / 15 |
Outcome results
Primary
C Reactive Protein
The proportional area-under-the-curve for plasma C reactive protein (CRP) levels measured during the first 3 days of admission. The proportion (y-axis) is calculated at each time-point with respect to the baseline CRP. The resultant y-axis is a unitless proportion. The x-axis is listed as days
Time frame: 3 days
Population: 1 patient in each group withdrew from the study prior to collection of data for the primary endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anakinra (Short) | C Reactive Protein | 2.09 days |
| Placebo | C Reactive Protein | 2.93 days |
Secondary
Brachial Artery Vasoreactivity
Change in flow mediated vasodilatation (FMD) of the brachial artery. Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter. The change is FMD is reported as the % change in FMD from baseline to 14 days.
Time frame: 14 days
Population: Some patients did not undergo assessment at 14 days because they did not show up to their scheduled appointment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anakinra (Short) | Brachial Artery Vasoreactivity | 41.7 percentage change |
| Placebo | Brachial Artery Vasoreactivity | -45.2 percentage change |
Secondary
Left Ventricular Ejection Fraction
Change in left ventricular ejection fraction (LVEF) between admission and 14 day follow up. This value is expressed as absolute change in measured LVEF. For example, if baseline LVEF = 20% and 14 day LVEF = 25%, this would be reported as an absolute change of 5%.
Time frame: 14 days
Population: Some patients did not undergo LVEF assessment at 14 days because they did not show up to their scheduled appointment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anakinra (Short) | Left Ventricular Ejection Fraction | 10 percent LVEF |
| Placebo | Left Ventricular Ejection Fraction | 0 percent LVEF |