A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial.
A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial.
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DOI：
10.1186/1745-6215-14-91
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发表时间：
2013-04-02
期刊：
影响因子：
2.5
通讯作者：
Solomon MA
中科院分区：
文献类型：
--
作者：
Elinoff JM;Rame JE;Forfia PR;Hall MK;Sun J;Gharib AM;Abd-Elmoniem K;Graninger G;Harper B;Danner RL;Solomon MA
肺动脉高压是一种与生存率低相关的罕见疾病。内皮功能障碍在肺动脉高压的发病机制和进展中起着核心作用。炎症似乎会导致这种功能失调的内皮表型，在患有特发性和疾病相关性肺动脉高压的遗传易感患者中传播损伤和修复的循环。针对肺血管炎症以中断损伤和修复周期从而延迟或预防右心室衰竭和死亡的治疗尚未经过测试。螺内酯是一种盐皮质激素和雄激素受体拮抗剂，已被证明可以改善内皮功能并减少炎症。目前对患有肺动脉高压和右心衰竭症状的患者的治疗包括使用盐皮质激素受体拮抗剂来发挥其利尿和利尿钠作用。我们假设，在肺动脉高压患者的疾病早期开始螺内酯治疗可以通过抗炎作用和改善肺血管功能提供额外的益处。 70 名无右心室衰竭临床证据的肺动脉高压患者将被纳入一项随机、双盲、安慰剂对照试验，以研究螺内酯早期治疗对运动能力、临床恶化和体内血管炎症的影响。我们的主要终点是与安慰剂相比，24 周时安慰剂校正的 6 分钟步行距离的变化以及螺内酯组临床恶化的发生率。在两侧 alpha 水平为 0.05 时，我们将至少有 84% 的功效来检测两组之间 6 分钟步行距离相对于基线的变化差异的 0.9 效应大小（组平均差除以标准差）。次要终点包括螺内酯对安慰剂校正最大耗氧量变化的影响；血管炎症的血浆标志物和外周血单核细胞基因表达谱；交感神经系统激活、肾素-血管紧张素-醛固酮系统激活和性激素代谢；使用超声心动图和新型高分辨率磁共振成像技术来了解右心室的结构和功能。将通过定期监测高钾血症和肾功能不全以及因不良反应而停药的发生率来评估螺内酯的安全性和耐受性。 ClinicalTrials.gov：NCT01712620
Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include the effect of spironolactone on the change in placebo-corrected maximal oxygen consumption; plasma markers of vascular inflammation and peripheral blood mononuclear cell gene expression profiles; sympathetic nervous system activation, renin-angiotensin-aldosterone system activation and sex hormone metabolism; and right ventricular structure and function using echocardiography and novel high-resolution magnetic resonance imaging-based techniques. Safety and tolerability of spironolactone will be assessed with periodic monitoring for hyperkalemia and renal insufficiency as well as the incidence of drug discontinuation for untoward effects. ClinicalTrials.gov: NCT01712620
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影响因子：
3.3
作者：
Abd-Elmoniem, Khaled Z.;Osman, Nael F.;Stuber, Matthias
通讯作者：
Stuber, Matthias
影响因子：
39.2
作者：
BARST, RJ;RUBIN, LJ;LEVY, PS
通讯作者：
LEVY, PS
影响因子：
4.6
作者：
Bendtzen, K;Hansen, PR;Rieneck, K
通讯作者：
Rieneck, K
DOI：
10.1164/rccm.201004-0601oc
发表时间：
2011-01-15
影响因子：
24.7
作者：
Arkles, Jeffrey S.;Opotowsky, Alexander R.;Forfia, Paul R.
通讯作者：
Forfia, Paul R.
DOI：
10.1016/s0735-1097(02)02164-2
发表时间：
2002-10-16
影响因子：
24
作者：
Gibbons, RJ;Balady, GJ;Smith, SC
通讯作者：
Smith, SC