Heart Failure
Conditions
Keywords
Heart failure, Inflammation, Interleukin-1, Cardiopulmonary exercise
Brief summary
This is an open-label, non-randomized, pilot-study to evaluate the effect of Interleukin-1 blockade on exercise capacity in patients with heart failure. Subjects will undergo cardiopulmonary exercise testing at baseline and after 2-weeks treatment with anakinra (recombinant human Interleukin-1 receptor antagonist).
Interventions
DRUGAnakinra
Anakinra 100 mg subcutaneous injection daily
Sponsors
National Institutes of Health (NIH)
National Center for Research Resources (NCRR)
Virginia Commonwealth University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of heart failure * Recent echocardiogram documenting left ventricular ejection fraction \<40% * High sensitivity C-reactive protein \>2 mg/L.
Exclusion criteria
* Recent changes (previous 3 months) in HF maintenance medications (beta-blockers, angiotensin converting enzyme \[ACE\] inhibitors, aldosterone antagonists, vasodilators, cardiac glycosides, diuretics) * Hospitalization for worsening HF or acute decompensated HF within the previous 12 months * Anticipated need for cardiac resynchronization therapy (CRT) or automated-implantable cardioverter defibrillator (AICD) * Angina or electrocardiograph (ECG) changes that limit maximum exertion during cardiopulmonary exercise testing or baseline ECG changes that limit the ability to detect ischemia (i.e. left bundle-branch block). * Recent (\<14 days) use of anti-inflammatory drugs (not including NSAIDs), chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus), malignancy, active infection, or any comorbidity limiting survival or ability to complete the study * Severe kidney dysfunction (eGFR \<30 mL/min) * Coagulopathy (INR \>1.5), thrombocytopenia (\<50,000/mm3), or leukopenia (absolute neutrophil count \<1,500/mm3) * Pregnancy (female patients will be required to take a urine pregnancy test) * Latex or rubber allergy * Inability to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Interval Change From Baseline in Peak VO2 | 14 days | Peak VO2 is a measurement of oxygen consumption rate during exercise (milliliters of oxygen per minute). It is calculated by continuous measurement of oxygen consumed during exercise while patients breath through a mask/tube. To account for variability in patient size, the oxygen consumption is divided by patient body weight. The outcome measure time frame was 14 days. This means that change in peak VO2 was calculated as the difference between peak VO2 at baseline and 14 days. To calculate this change, we used the mathematical process of subtraction (change in peak VO2 = Peak VO2 \[day 14\] - Peak VO2 \[baseline\]) |
| Median Interval Change From Baseline in the Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope) | 14 days | The VE/VCO2 slope is calculated as the ratio of minute ventilation (VE) and carbon dioxide production (VCO2). Because these measurements share the same units, the resultant ratio is unitless. Change in VE/VCO2 slope was calculated as the change in VE/VCO2 slope between baseline and 14 days. We therefore calculated the difference between VE/VCO2 slope measurements that occurred at baseline and at 14 days (change in VE/VCO2 slope = VE/VCO2 slope \[day 14\] - VE/VCO2 slope \[baseline\]) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI) | 14 days | The Duke Activity Status Index (DASI) is a scale that quantifies patients' ability to perform various tasks. The scale ranges from 0 (unable to perform any tasks) to 58.20 (able to perform all tasks). Higher scores reflect improved activity or improved heart failure symptoms. Lower scores reflect worsened ability or worsened heart failure symptoms. |
Other
| Measure | Time frame |
|---|---|
| Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide) | 14 days |
| Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2 | 14 days |
Countries
United States
Participant flow
Recruitment details
11 patients had elevated hsCRP (\>2 mg/L) and were enrolled in the study.
Pre-assignment details
2 patients withdrew consent prior to beginning the study. 1 patient underwent a change in heart failure medication prior to beginning the study and was therefore withdrawn from the study. The 8 remaining patients began the study interventions.
Participants by arm
| Arm | Count |
|---|---|
| Anakinra | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Anakinra |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 55 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Median Interval Change From Baseline in Peak VO2
Peak VO2 is a measurement of oxygen consumption rate during exercise (milliliters of oxygen per minute). It is calculated by continuous measurement of oxygen consumed during exercise while patients breath through a mask/tube. To account for variability in patient size, the oxygen consumption is divided by patient body weight. The outcome measure time frame was 14 days. This means that change in peak VO2 was calculated as the difference between peak VO2 at baseline and 14 days. To calculate this change, we used the mathematical process of subtraction (change in peak VO2 = Peak VO2 \[day 14\] - Peak VO2 \[baseline\])
Time frame: 14 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anakinra | Median Interval Change From Baseline in Peak VO2 | 3.90 mL/kg/min |
Primary
Median Interval Change From Baseline in the Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope)
The VE/VCO2 slope is calculated as the ratio of minute ventilation (VE) and carbon dioxide production (VCO2). Because these measurements share the same units, the resultant ratio is unitless. Change in VE/VCO2 slope was calculated as the change in VE/VCO2 slope between baseline and 14 days. We therefore calculated the difference between VE/VCO2 slope measurements that occurred at baseline and at 14 days (change in VE/VCO2 slope = VE/VCO2 slope \[day 14\] - VE/VCO2 slope \[baseline\])
Time frame: 14 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anakinra | Median Interval Change From Baseline in the Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope) | -2.10 (unitless) |
Secondary
Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI)
The Duke Activity Status Index (DASI) is a scale that quantifies patients' ability to perform various tasks. The scale ranges from 0 (unable to perform any tasks) to 58.20 (able to perform all tasks). Higher scores reflect improved activity or improved heart failure symptoms. Lower scores reflect worsened ability or worsened heart failure symptoms.
Time frame: 14 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anakinra | Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI) | 6 units on a scale |
Other Pre-specified
Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2
Time frame: 14 days
Other Pre-specified
Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide)
Time frame: 14 days