Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Heart Failure

Study Overview
=================
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).

Official Title
-----------------
Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Heart Failure

Conditions
-----------------
Heart Failure

Intervention / Treatment
-----------------
* Drug: Anakinra


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anakinra<br> | Drug: Anakinra<br>* Anakinra 100 mg subcutaneous injection daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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]) | 14 days | 
| 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]) | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 14 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Heart failure, Inflammation, Interleukin-1, Cardiopulmonary exercise