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The Effects of Interleukin-1 Blockade On Exercise Capacity In Patients With Recently Decompensated Systolic Heart Failure

IL-1 阻断对近期失代偿性收缩性心力衰竭患者运动能力的影响

基本信息

批准号：
9760411
负责人：
Antonio Abbate
金额：
$ 54.71万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9760411
关键词：
Activities of Daily Living Acute Admission activity Aerobic Exercise Aldosterone Angiotensin II Animal Model Anti-inflammatory Blood Vessels Breathing Cardiac Cardiopulmonary Clinical Clinical Trials Complex Coupling Data Diagnosis Disease Disease Marker Disease Progression Doctor of Pharmacy Doctor of Philosophy Doppler Echocardiography Double-Blind Method EFRAC Event Exertion Fatigue Fingers Functional disorder Heart failure Hospitalization Hospitals Human Impairment Incidence Inflammation Inflammatory Inflammatory Response Interleukin-1 Interruption Knowledge Life Expectancy Measures Mediator of activation protein Morbidity - disease rate Myocardial Norepinephrine Outcome Oxygen Oxygen Consumption Pathway interactions Patients Performance Pharmacology Phase Phase II Clinical Trials Phase III Clinical Trials Pilot Projects Placebos Play Plethysmography Prevalence Quality of life Randomized Recombinants Relaxation Reporting Research Personnel Risk Factors Role Site Stroke Symptoms Syndrome Systolic heart failure Testing Work adjudication adverse outcome anakinra cardiac depression cost cytokine design disease natural history exercise capacity follow-up functional disability heart function hemodynamics hospital readmission human old age (65+)improved mortality novel novel therapeutic intervention older patient outcome forecast pressure primary endpoint readmission rates reduce symptoms secondary endpoint therapy design treatment optimization treatment strategy uptake

项目摘要

Project Summary This application is for a Single-Site Investigator-Initiated Clinical Trial (R61/R33) entitled “Effects of Interleukin-1 blockade on exercise capacity in patients with recently decompensated systolic heart failure” submitted by Antonio Abbate MD, PhD and Benjamin Van Tassell, PharmD. Heart failure (HF) is a complex clinical syndrome characterized by fatigue and labored breathing upon exertion. Although current treatment options have extended life expectancy, prognosis for HF remains poor and HF is the leading cause of admission among elderly patients in the US. There is an urgent need to develop novel treatments to alleviate symptoms, slow disease progression, and reduce HF hospitalization. A significant correlation exists between declining cardiac function and increasing levels of inflammatory cytokines in HF patients. Among these cytokines, Interleukin-1 (IL-1) is a key mediator of systemic inflammation that becomes elevated in HF patients and may contribute to poor cardiac function. In animal models of HF, IL-1 is sufficient to cause significant depression of cardiac function, impaired cardiac reserve, and worsened cardiac remodeling. In a recent pilot study, 12 weeks treatment with recombinant human IL-1 receptor antagonist (IL-1Ra, anakinra) produced a significant improvement in aerobic exercise performance as measured by peak oxygen consumption (VO2). This proposal will support a randomized, double-blind, phase II clinical trial (n=102) to confirm the effect of IL-1 blockade to improve exercise capacity in HF patients and estimate the potential benefit of IL-1 blockade on HF readmission in patients with recently decompensated heart failure (HF). Eligible patients will be randomized to 24 weeks treatment with anakinra (n=68) or placebo (n=34). Results from this study will be used to optimize the treatment strategy and design a subsequent phase III clinical trial to evaluate long-term morbidity and mortality with IL-1 blockade in HF patients.

项目摘要本申请是一项由调查员发起的名为“Effect of”的临床试验白介素1阻断近期失代偿性收缩心力衰竭患者的运动能力作者：Antonio Abbate，医学博士和Benjamin Van Tassell，制药博士。心力衰竭(HF)是一种复杂的疾病以劳累和劳累时呼吸困难为特征的临床综合征。尽管目前的治疗方法选择延长了预期寿命，心力衰竭的预后仍然很差，心力衰竭是导致美国老年患者的入院情况。迫切需要开发新的治疗方法来缓解症状，延缓疾病进展，减少心力衰竭住院时间。心功能下降与炎症水平升高之间存在显著的相关性心衰患者的细胞因子。在这些细胞因子中，白介素1(IL-1)是系统性红斑狼疮的关键介质。炎症在心力衰竭患者中升高，可能导致心功能不佳。在动物身上模型的HF，IL-1足以引起心功能的显著抑制，心脏储备受损，并加重心脏重塑。在最近的一项试点研究中，重组人IL-1治疗12周受体拮抗剂(IL-1ra，anakinra)可显著改善有氧运动成绩以最大耗氧量(VO2)衡量。这项建议将支持一项随机、双盲、II期临床试验(n=102)以确认疗效。 IL-1阻断改善心力衰竭患者运动能力及评价IL-1阻断的潜在益处近期失代偿性心力衰竭(心衰)患者再次入院的情况。符合条件的患者将是随机接受阿纳金拉(n=68)或安慰剂(n=34)治疗24周。这项研究的结果将被用于优化治疗策略并设计后续的III期临床试验，以评估长期疗效 IL-1阻断治疗心力衰竭患者的发病率和死亡率。