Interleukin-1 Blockade in HF With Preserved EF
Condition: Heart Failure With Normal Ejection Fraction
MeSH terms: Heart Failure
Intervention: Anakinra; Placebo
Intervention MeSH terms: Interleukin 1 Receptor Antagonist Protein
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 31.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No
Keywords: heart failure; HFpEF; diastole; diastolic heart failure; inflammation; interleukin-1; C-reactive protein

Summary:

      -  Heart Failure with Preserved Ejection Fraction (HFpEF) is a common form of heart failure

        -  Standard treatment for heart failure, show less than ideal results in HFpEF

        -  Evidence of systemic inflammation is common in all forms of heart failure, including
           HFpEF

        -  The main hypothesis of this study is that systemic inflammation contributes to heart
           failure symptoms and exercise limitations in patients with HFpEF

        -  The main objective is to treat patients with HFpEF and evidence of systemic inflammation
           with an anti-inflammatory drug targeting Interleukin-1 (or placebo) to determine effects
           on cardiovascular function
    

Eligibility criteria:

        Inclusion Criteria:

          1. Symptoms and signs of heart failure (NYHA II-III) and prior hospitalization for heart
             failure

          2. Recent Imaging Study (<12 months) showing LVEF>50% and Left Ventricular End Diastolic
             Volume Index (LVEDVI) <97ml/m2

          3. Evidence of abnormal LV relaxation, filling, diastolic distensibility, and diastolic
             stiffness as shown by one of the following

             a. Invasive Hemodynamic measurements i. mean Pulmonary Capillary Wedge Pressure (mPCW)
             >12 ii. Left Ventricular End Diastolic Pressure (LVEDP) >16 mmHg b. Tissue Doppler
             Echocardiogram i. E/E' >15 ii. E/E' 8-15 and one of the following: Left Ventricular
             Hypertrophy (LVH), Atrial fibrillation, Left Atrial Enlargement (LAE), E/A <0.5 + DT
             (Deceleration Time) >280, c. Biomarkers i. Brain Natriuretic Peptide (BNP) >200pg/ml
             (not due to a concomitant disease such as pulmonary arterial hypertension, pulmonary
             embolism, acute renal failure, or other)

          4. CRP > 2.0 mg/L

        Exclusion Criteria:

          -  Age <21

          -  Concomitant conditions or treatments which would affect completion of the study or
             interpretation of the study tests including but not limited to the following
             conditions:

               -  physical inability to walk or run on a treadmill

               -  angina or evidence of spontaneous or inducible ischemia

               -  uncontrolled arterial hypertension

               -  atrial fibrillation (or other arrhythmias)

               -  moderate to severe valvular heart disease

               -  chronic pulmonary disease

               -  anemia (Hgb<10 g/dl)

          -  Angina, uncontrolled hypertension or electrocardiograph (ECG) changes (i.e. ischemia,
             arrhythmias) that limit maximum exertion during cardiopulmonary exercise testing

          -  Anticipated need for cardiac resynchronization therapy (CRT) or automated-implantable
             cardioverter defibrillator (AICD) or coronary revascularization or cardiac surgery

          -  Active infection including chronic infection

          -  Active cancer (or prior diagnosis of cancer within the past 10 years)

          -  Recent (<14 days) or active use of immunosuppressive drugs (including but not limited
             to high-dose corticosteroids [>1_mg/kg of prednisone equivalent], Tumor Necrosis
             Factor (TNF)-α blockers, cyclosporine) not including Non-Steroidal Anti-Inflammatory
             Drugs (NSAIDs) or corticosteroids used for IV dye allergy only)

          -  Chronic auto-immune or auto-inflammatory disease (including but not limited to
             rheumatoid arthritis, systemic lupus erythematosus)

          -  Neutropenia (absolute neutrophil count<1,800/mm3 [or <1,000/mm3 in African-American
             patients])

          -  Severe impairment in renal function (estimated glomerular filtration rate <30
             ml/kg*min)

          -  Recent or planned use of vaccination with live attenuated viruses

          -  Allergy to rubber or latex

          -  Allergy to products derived from Escherichia coli

          -  Pregnancy or breastfeeding

          -  Inability to give informed consent