The REPAIR Study,JACC: Cardiovascular Imaging

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The REPAIR Study
JACC: Cardiovascular Imaging ( IF 12.8 ) Pub Date : 2021-11-17 , DOI: 10.1016/j.jcmg.2021.07.027
Anton Vonk Noordegraaf ₁ , Richard Channick ₂ , Emmanuelle Cottreel ₃ , David G Kiely ₄ , J Tim Marcus ₁ , Nicolas Martin ₃ , Olga Moiseeva ₅ , Andrew Peacock ₆ , Andrew J Swift ₇ , Ahmed Tawakol ₈ , Adam Torbicki ₉ , Stephan Rosenkranz ₁₀ , Nazzareno Galiè ₁₁

Affiliation

Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom.
Almazov National Medical Research Centre, St. Petersburg, Russia.
Scottish Pulmonary Vascular Unit, Glasgow, United Kingdom.
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology, Centre of Postgraduate Medical Education, ECZ-Otwock, Otwock, Poland.
Department of Cardiology, Heart Center at the University of Cologne, and Cologne Cardiovascular Research Center (CCRC), Cologne, Germany.
Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.

Objectives

The REPAIR (Right vEntricular remodeling in Pulmonary ArterIal hypeRtension) study evaluated the effect of macitentan on right ventricular (RV) and hemodynamic outcomes in patients with pulmonary arterial hypertension (PAH), using cardiac magnetic resonance (CMR) and right heart catheterization (RHC).

Background

RV failure is the primary cause of death in PAH. CMR is regarded as the most accurate noninvasive method for assessing RV function and remodeling and CMR measures of RV function and structure are strongly prognostic for survival in patients with PAH. Despite this, CMR is not routinely used in PAH clinical trials.

Methods

REPAIR was a 52-week, open-label, single-arm, multicenter, phase 4 study evaluating the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition, on RV remodeling and function and cardiopulmonary hemodynamics. Primary endpoints were change from baseline to week 26 in RV stroke volume, determined by CMR; and pulmonary vascular resistance, determined by RHC. Efficacy measures were assessed for all patients with baseline and week 26 data for both primary endpoints.

Results

At a prespecified interim analysis in 42 patients, both primary endpoints were met, enrollment was stopped, and the study was declared positive. At final analysis (n = 71), RV stroke volume increased by 12 mL (96% confidence level: 8.4-15.6 mL; P < 0.0001) and pulmonary vascular resistance decreased by 38% (99% confidence level: 31%-44%; P < 0.0001) at week 26. Significant positive changes were also observed in secondary and exploratory CMR (RV and left ventricular), hemodynamic, and functional endpoints at week 26. Improvements in CMR RV and left ventricular variables and functional parameters were maintained at week 52. Safety (n = 87) was consistent with previous clinical trials.

Conclusions

In the context of this study, macitentan treatment in patients with PAH resulted in significant and clinically-relevant improvements in RV function and structure and cardiopulmonary hemodynamics. At 52 weeks, improvements in RV function and structure were sustained. (REPAIR: Right vEntricular remodeling in Pulmonary ArterIal hypeRtension [REPAIR]; NCT02310672)

中文翻译：

维修研究

目标

REPAIR（肺动脉高压的右心室重塑）研究使用心脏磁共振（CMR）和右心导管插入术（RHC）评估了马西替坦对肺动脉高压（PAH）患者右心室（RV）和血流动力学结果的影响.

背景

RV 衰竭是 PAH 死亡的主要原因。CMR 被认为是评估 RV 功能和重塑的最准确的无创方法，并且 RV 功能和结构的 CMR 测量值对 PAH 患者的生存具有强烈的预后意义。尽管如此，CMR 并未常规用于 PAH 临床试验。

方法

REPAIR 是一项为期 52 周、开放标签、单臂、多中心、4 期研究，评估 10 mg macitentan（有或没有 5 型磷酸二酯酶抑制）对 RV 重塑和功能以及心肺血流动力学的影响。主要终点是 RV 每搏输出量从基线到第 26 周的变化，由 CMR 确定；和肺血管阻力，由 RHC 确定。对所有具有基线和第 26 周两个主要终点数据的患者的疗效指标进行了评估。

结果

在对 42 名患者进行的预先指定的中期分析中，两个主要终点均得到满足，停止入组，并宣布该研究为阳性。在最终分析 (n = 71) 时，右室每搏输出量增加了 12 mL（96% 置信水平：8.4-15.6 mL；P < 0.0001），肺血管阻力降低了 38%（99% 置信水平：31%-44% ; P < 0.0001) 在第 26 周。在第 26 周时，在继发性和探索性 CMR（RV 和左心室）、血流动力学和功能终点方面也观察到了显着的积极变化。CMR RV 和左心室变量和功能参数的改善保持在第 52 周。安全性 (n = 87) 与之前的临床试验一致。