Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Pauley Heart Center, Richmond, VA, USA.
Department of Pharmacotherapy and Outcome Sciences, Virginia Commonwealth University, Richmond, VA, USA.
J Transl Med. 2022 Jun 15;20(1):270. doi: 10.1186/s12967-022-03466-9.
Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF.
We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes.
The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF.
The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.
尽管实施了指南指导的治疗，但心力衰竭（HF）仍是全球主要的死亡原因，因此需要新的治疗策略。白细胞介素-1（IL-1）受体拮抗剂阿那白滞素的概念验证临床试验表明，该药在心力衰竭患者中具有良好的疗效。
我们设计了一项单中心、随机、安慰剂对照、双盲 II 期随机临床试验。102 例成人患者在急性失代偿性射血分数降低心力衰竭（HFrEF）和全身炎症（高敏 C 反应蛋白>2mg/L）出院后 2 周内住院，将以 2:1 的比例随机分为接受阿那白滞素或安慰剂治疗 24 周。主要目的是确定阿那白滞素对 24 周治疗后心肺运动试验（CPX）时峰值摄氧量（VO）的影响，以 CPX 后 24 周的峰值 VO 校正安慰剂（或最长的可用随访）的变化。次要探索性终点将评估阿那白滞素对其他 CPX 参数、结构和功能超声心动图数据、无创血流动力学、生活质量问卷、生物标志物和心力衰竭结局的影响。
目前的试验将评估 IL-1 阻断剂阿那白滞素在急性失代偿性 HFrEF 近期住院患者中使用 24 周对心肺适能的影响。
该试验于 2019 年 1 月 8 日前瞻性地在 ClinicalTrials.gov 注册，标识符为 NCT03797001。
