Effects of volenrelaxin in worsening heart failure with preserved ejection fraction: a phase 2 randomized trial.

In this study, we conducted a double-blind, international, multicenter trial to test whether volenrelaxin, a long-acting form of human relaxin, can improve left atrial (LA) function, reduce congestion and improve kidney function in patients with heart failure and preserved ejection fraction (HFpEF).

在这项研究中，我们进行了一项双盲、国际、多中心的试验，以测试 volenrelaxin（一种长效的人类 relaxin 形式）是否能改善左心房（LA）功能，减少充血并改善具有心力衰竭和保留射血分数（HFpEF）的患者的肾功能。

We randomly assigned patients with New York Heart Association (NYHA) class II-IV HFpEF and recent heart failure (HF) decompensation to 25-mg, 50-mg or 100-mg volenrelaxin or placebo administered subcutaneously once weekly.

我们随机分配了纽约心脏病协会（NYHA）II-IV级射血分数保留的心力衰竭（HFpEF）患者以及最近出现心力衰竭（HF）失代偿的患者，接受每周一次皮下注射25毫克、50毫克或100毫克的volenrelaxin或安慰剂治疗。

The primary outcome was the change in LA reservoir strain at 26 weeks, with key secondary endpoints including changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR) and safety.

主要结果是26周时左心房储备应变的变化，关键次要终点包括N末端前体B型利钠肽（NT-proBNP）、估算的肾小球滤过率（eGFR）的变化以及安全性。

The trial was stopped early by the sponsor because of evidence for worsening congestion after 332 participants had been enrolled (mean age 74 years, 49% women, mean body mass index 30.6 kg m-2, 31.9% NYHA class III-IV).

由于在332名参与者入组后（平均年龄74岁，49%为女性，平均体重指数为30.6 kg/m²，31.9%为纽约心脏病协会（NYHA）III-IV级）出现恶化性充血的证据，赞助商提前终止了该试验。

Compared to placebo, 25-mg volenrelaxin improved LA reservoir strain (+3.9%, 95% confidence interval(CI): 1.1-6.6, P = 0.006) but did not have effects on this outcome at 50-mg (+1.3%, 95% CI: -1.3 to 3.9, P = 0.332) or 100-mg (+0.9%, 95% CI: -1.8 to 3.6, P = 0.521) doses.

与安慰剂相比，25毫克的volenrelaxin改善了左心房储备应变（+3.9%，95%置信区间（CI）：1.1-6.6，P = 0.006），但在50毫克（+1.3%，95% CI：-1.3至3.9，P = 0.332）或100毫克（+0.9%，95% CI：-1.8至3.6，P = 0.521）剂量下对这一结果没有影响。

At 26 weeks, volenrelaxin (pooling all dosages) increased NT-proBNP levels (+24.5%, 95% CI: 2.0-51.8) and had no significant effect on eGFR (+2.2 ml min-1 1.73 m-2, 95% CI: -1.8 to 6.3).

在26周时，将所有剂量的volenrelaxin合并后，NT-proBNP水平增加了（+24.5%，95%置信区间：2.0-51.8），对eGFR没有显著影响（+2.2 ml min-1 1.73 m-2，95%置信区间：-1.8到6.3）。

Volenrelaxin was also associated with a non-significant increase in risk for HF hospitalization compared to placebo (hazard ratio= 2.64, 95% CI: 0.93-7.56, P = 0.070), along with signals for an increased number of cardiovascular and renal serious adverse events (odds ratio = 2.52, 95% CI: 0.95-6.68, P = 0.056).

与安慰剂相比，volenrelaxin还与心力衰竭住院风险的非显著增加有关（风险比=2.64，95%置信区间：0.93-7.56，P = 0.070），以及心血管和肾脏严重不良事件数量增加的信号（优势比=2.52，95%置信区间：0.95-6.68，P = 0.056）。

In conclusion, despite some evidence for improvement in LA function at a low dose, treatment with this long-acting form of human relaxin was associated with worsening congestion in patients with recently decompensated HFpEF.

总之，尽管有证据表明低剂量下左房功能有所改善，但使用这种长效人松弛素治疗的患者中，近期失代偿的射血分数保留型心力衰竭（HFpEF）患者出现充血症状恶化。

ClinicalTrials.gov identifier: NCT05592275 .

ClinicalTrials.gov注册号：NCT05592275。