Pilot Feasibility Study of the Safety and Efficacy of Anakinra in Heart Failure With Preserved Ejection Fraction

Study Overview
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Brief Summary
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This will be a randomized, double-blind, crossover pilot study to measure the safety and feasibility of Interleukin-1 (IL-1) blockade with Anakinra in patients with stable heart failure with preserved ejection fraction.

Official Title
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Pilot Feasibility Study of the Safety and Efficacy of Anakinra in Heart Failure With Preserved Ejection Fraction

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Anakinra
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms and signs of congestive heart failure Recent Imaging Study (<12 months) showing Left Ventricular Ejection Fraction (LVEF) >50% and Left Ventricular End Diastolic Volume Index (LVEDVI) <97ml/m2 Evidence of abnormal Left Ventricular (LV) relaxation, filling, diastolic distensibility, and diastolic stiffness as shown by one of the following: Invasive Hemodynamic measurements mean Pulmonary Capillary Wedge pressure (mPCW) >12 Left Ventricular End Diastolic Pressure (LVEDP) >16 mmHg Tissue Doppler Echocardiogram E/E' >15 E/E' 8-15 and one of the following Left Ventricular Hypertrophy (LVH) Atrial Fibrillation Left Atrial Enlargement E/A <0.5 + Deceleration Time (DT) >280 (if >50yrs of age) Biomarkers Brain Natriuretic Peptide (BNP) >200pg/mL Exclusion Criteria: Age <18 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 Heart Failure (HF) or acute decompensated HF within the previous 12months 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 Active infection including chronic infection Active cancer Recent (<14 days) use of anti-inflammatory drugs (not including Non-Steroidal Anti-Inflammatory Drugs [NSAIDs]), Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus), malignancy, or any comorbidity limiting survival or ability to complete the study Pregnancy (determined by urine pregnancy test in women of childbearing potential) Inability to give informed consent Other conditions limiting completion of cardiopulmonary exercise test or completion of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anakinra<br>Treatment with daily subcutaneous injections of Anakinra 100 mg | Drug: Anakinra<br>* Anakinra 100 mg daily subcutaneous injection<br>* Other names: Kineret;|
| Placebo Comparator: Placebo<br>Treatment with daily subcutaneous injection of placebo | Drug: Placebo<br>* Placebo daily subcutaneous injection<br>* Other names: Sodium Chloride (NaCl) 0.9%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Oxygen Consumption (Peak VO2) | The primary endpoint is the change in peak oxygen consumption among stable heart failure patients (n = 12) following 14-days treatment with daily doses of Anakinra 100 mg (SC, subcutaneous). | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise Time | Interval change from baseline in duration of exercise during a standardized cardiopulmonary exercise test upon completion of 2 weeks treatment | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure with preserved ejection fraction, Diastolic heart failure, Aerobic exercise performance