重新利用丙磺舒治疗心力衰竭（Re-Prosper-HF）：一项随机安慰剂对照临床试验的研究方案。
Repurposing Probenecid for the Treatment of Heart Failure (Re-Prosper-HF): a study protocol for a randomized placebo-controlled clinical trial.
机构信息
Division of Cardiovascular Medicine, Cincinnati Veterans Affairs Medical Center, 3200 Vine St, Cincinnati, OH, 45220, USA.
Department of Internal Medicine, Division of Cardiovascular Diseases, College of Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA.
出版信息
Trials. 2022 Apr 7;23(1):266. doi: 10.1186/s13063-022-06214-y.
BACKGROUND
Improving contractility in heart failure with reduced ejection fraction (HFrEF) has resurfaced as a potential treatment goal. Inotropic therapy is now better understood through its underlying mechanism as opposed to the observed effect of increasing contractility. Calcitropes are a subgroup of inotropes that largely depend on the stimulation of adenylyl cyclase to transform ATP into cyclic adenosine monophosphate (cAMP). At least two clinically relevant calcitropes-istaroxime and probenecid-improve contractility through an increase in systolic intracellular calcium without activating cAMP production. Probenecid, which has been safely used clinically for decades in non-cardiac conditions, has recently been identified as an agonist of the transient receptor potential vanilloid 2 channel. Translational studies have shown that it improves calcium cycling and contractility without activating noxious pathways associated with cAMP-dependent calcitropes and can improve cardiac function in patients with HFrEF.
METHODS
The Re-Prosper-HF study (Repurposing Probenecid for the Treatment of Heart Failure with Reduced Ejection Fraction) is a three-site double-blinded randomized-controlled trial that will test the hypothesis that probenecid can improve cardiac function in patients with HFrEF. Up to 120 patients will be randomized in this double-blind, placebo-controlled study that will assess whether oral probenecid administered at 1 g orally twice per day for 180 days in patients with NYHA II-III HFrEF improves systolic function (aim 1), functional status (aim 2), and self-reported health status (aim 3).
DISCUSSION
Findings from this study will provide data informing its use for improving symptomatology in patients with HFrEF as well as exploratory data for outcomes such as hospital admission rates.
TRIAL TEGISTRATION
The Re-Prosper HF Study (Re-Prosper HF) is registered on ClinicalTrials.gov with the identifier as NCT04551222. Registered on 9 September 2020.
背景
改善射血分数降低的心力衰竭（HFrEF）的收缩性已经重新成为一个潜在的治疗目标。通过了解其潜在机制，而非观察到的增加收缩性的效果，人们现在对正性肌力药物治疗有了更好的理解。钙敏感受体激动剂是正性肌力药物的一个亚类，主要依赖于刺激腺苷酸环化酶将三磷酸腺苷转化为环磷酸腺苷（cAMP）。至少有两种临床上相关的钙敏感受体激动剂-伊司他洛米和丙磺舒-通过增加细胞内收缩期钙而不激活 cAMP 产生来改善收缩性。丙磺舒在非心脏疾病的临床应用已有几十年的历史，最近被确定为瞬时受体电位香草酸 2 通道的激动剂。转化研究表明，它可以改善钙循环和收缩性，而不会激活与 cAMP 依赖性钙敏感受体激动剂相关的有害途径，并可以改善 HFrEF 患者的心脏功能。
方法
Re-Prosper-HF 研究（丙磺舒治疗射血分数降低的心力衰竭的再利用）是一项三地点双盲随机对照试验，将检验丙磺舒是否能改善 HFrEF 患者的心脏功能的假设。这项双盲、安慰剂对照研究将纳入多达 120 名患者，评估 HFrEF II-III 级 NYHA 患者每天口服丙磺舒 1 克，每日两次，持续 180 天，是否能改善收缩功能（主要目标 1）、功能状态（主要目标 2）和自我报告的健康状况（主要目标 3）。
讨论
该研究的结果将提供数据，为改善 HFrEF 患者的症状提供信息，并为住院率等结果提供探索性数据。
试验注册
Re-Prosper HF 研究（Re-Prosper HF）在 ClinicalTrials.gov 上注册，标识符为 NCT04551222。于 2020 年 9 月 9 日注册。
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