BackgroundThe VITALITY-HFpEF trial (Evaluate the Efficacy and Safety of the Oral sGC Stimulator Vericiguat to Improve Physical Functioning in Daily Living Activities of Patients With Heart Failure and Preserved Ejection Fraction) is designed to determine the efficacy and safety of a novel oral soluble guanylate cyclase stimulator, vericiguat, on quality of life and exercise tolerance in heart failure patients with preserved ejection fraction (HFpEF). Impaired physical functioning reduces the quality of life in patients with HFpEF. The primary goal of HF treatment along with improving survival is to improve function, reduce symptoms, and maximize quality of life. Abnormal cyclic guanosine monophosphate signaling may contribute to physical limitations in patients with HFpEF via central and peripheral mechanisms. Exploratory post hoc analyses from a prior trial showed that vericiguat can improve patient-relevant domains of the Kansas City Cardiomyopathy Questionnaire, especially the physical limitation score.Methods and ResultsVITALITY-HFpEF is a placebo-controlled, double-blind, multi-center, phase IIb trial of ≈735 patients, ≥45 years with HFpEF and ejection fraction ≥45% who will be randomized 1:1:1 to placebo, 10 mg, or 15 mg vericiguat. The primary end point is change in Kansas City Cardiomyopathy Questionnaire physical limitation score from baseline to week 24 and change in 6-minute walk test from baseline to week 24 is the secondary end point.ConclusionsVITALITY-HFpEF is the first trial designed to assess the efficacy of vericiguat in patients with HFpEF using the Kansas City Cardiomyopathy Questionnaire physical limitation score as a novel primary end point. This study will also extend the prior dosing experience with vericiguat in HF by studying the safety and efficacy of a 15 mg dose.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT03547583.

中文翻译：

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VITALITY-HFpEF试验的原理和设计。

背景VITALITY-HFpEF试验（评估口服sGC刺激剂Vericiguat改善心力衰竭和保留射血分数患者日常生活活动中的身体功能的功效和安全性）旨在确定新型口服可溶性鸟苷酸环化酶的疗效和安全性刺激剂对维持射血分数（HFpEF）的心力衰竭患者的生活质量和运动耐量的影响。身体功能受损会降低HFpEF患者的生活质量。HF治疗与改善生存率的主要目标是改善功能，减轻症状并最大限度地提高生活质量。环状鸟苷单磷酸信号异常可能是通过中枢和外周机制导致HFpEF患者的身体局限性。一项先前试验的事后探索性分析显示，Vericiguat可以改善堪萨斯城心肌病问卷的患者相关领域，尤其是身体限制评分。方法和结果VITALITY-HFpEF是安慰剂对照，双盲，多中心，阶段约735名HFpEF≥45岁且射血分数≥45％的患者的IIb试验​​，将以1：1：1：1的比例随机分配至安慰剂，10 mg或15 mg vericiguat。主要终点是从基线到第24周的堪萨斯城心肌病问卷调查身体极限评分的变化，从基线到第24周的6分钟步行测试的变化是次要终点。结论：VITALITY-HFpEF是第一个以堪萨斯城心肌病问卷物理限制评分为新的主要终点评估Vericguat在HFpEF患者中的疗效的试验。这项研究还将通过研究15 mg剂量的安全性和有效性来扩展Vericiguat在HF中的先后给药经验。临床试验注册网址：https：//www.clinicaltrials.gov。唯一标识符：NCT03547583。