Interleukin-1 Blockade in HF With Preserved EF

• Status: Completed
• Trial end date: 2017-06-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Virginia Commonwealth University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Interleukin 1 Receptor Antagonist Protein

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