Interleukin-1 Blockade in Heart Failure With Preserved Ejection Fraction (HFpEF): a Randomized Placebo-controlled Double Blinded Study (D-HART2)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Change in Aerobic Exercise Capacity
研究概览
简要总结
- 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
详细描述
Heart Failure with Preserved Ejection Fraction (HFpEF) is a common form of heart failure, characterized by symptoms of congestion and impaired exercise tolerance, secondary to impaired left ventricular filling (diastole) in absence of a significant impairment in contractility (LVEF>50%) or significant valvular abnormalities, shunts or intra- or extra-cavitary obstruction.
The standard treatment for patient with heart failure is very effective in Heart Failure with Reduced Ejection Fraction (HFrEF), but it not very effective in HFpEF.
Evidence of systemic inflammation is common in all forms of heart failure, including HFpEF, and predicts worse outcomes. C reactive protein (CRP) is the preferred inflammatory biomarker used as risk predictor for cardiovascular disease. Patients with heart failure (HFpEF or HFrEF) with elevated CRP levels are more likely to be severely limited by heart failure symptoms, are more likely to be admitted to the hospital for heart failure, and are more likely to die of cardiac causes.
Preclinical studies show that a key mediator of systemic inflammation, Interleukin-1 (IL-1), impairs cardiac and vascular function, and may contribute to the pathogenesis of heart failure.
The main hypothesis of this study is that systemic inflammation, and IL-1 in particular, contributes to heart failure symptoms and exercise limitations in patients with HFpEF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptoms and signs of heart failure (NYHA II-III) and prior hospitalization for heart failure
- •Recent Imaging Study (<12 months) showing LVEF>50% and Left Ventricular End Diastolic Volume Index (LVEDVI) <97ml/m2
- •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)
- •CRP > 2.0 mg/L
排除标准
- •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
研究组 & 干预措施
Anakinra
Anakinra 100 mg given subcutaneously once daily for 12 weeks
干预措施: Anakinra (Drug)
Placebo
Matching Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Aerobic Exercise Capacity
时间窗: Baseline to 12 weeks
Absolute changes in aerobic exercise capacity (peak VO2) after 12 weeks treatment. This will compare patients treated with anakinra and provide a randomized, double-blinded assessment of the effects of IL-1β blockade on aerobic exercise performance.
Change in Ventilatory Eefficiency
时间窗: Baseline to 12 weeks
Absolute changes in ventilatory efficiency (VE/VCO2 \[carbon dioxide\] slope) after 12 weeks treatment. This will compare patients treated with anakinra vs placebo, and provide a randomized, double-blinded assessment of the effects of IL-1β blockade on aerobic exercise performance.
次要结局
- Echocardiographic Assessment of Diastolic and Systolic Function (Left Ventricular Ejection Fraction)(12 weeks)
- Hospital Admission for Acute Decompensated Heart Failure(24 weeks)
- Change in Diastolic and Contractile Reserve (e' Velocity and E/e' Ratio)(Baseline to 12 weeks)
- Change in Quality of Life Questionnaire-Minnesota Living With Heart Failure Questionnaire (MLWHF)(Baseline to 24 weeks)
- Change in Quality of Life Questionnaire-Duke Activity Status Index (DASI)(Baseline to 12 weeks)
- Change in Inflammation (C Reactive Protein Levels)(Baseline to 12 weeks)