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

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)可显著提高有氧运动成绩 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。

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.