University of Michigan Health System, CVC Cardiovascular Medicine, Ann Arbor, Michigan 48109-5853, USA.
J Am Coll Cardiol. 2010 May 4;55(18):1915-22. doi: 10.1016/j.jacc.2010.01.027.
This study assessed the efficacy and safety of inhaled treprostinil in pulmonary arterial hypertension (PAH) patients receiving therapy with either bosentan or sildenafil.
There is no cure for PAH, despite effective treatments, and outcomes remain suboptimal. The addition of inhaled treprostinil, a long-acting prostacyclin analog, might be a safe and effective treatment addition to other PAH-specific oral therapies.
Two hundred thirty-five PAH patients with New York Heart Association (NYHA) functional class III (98%) or IV symptoms and a 6-min walk distance (6MWD) of 200 to 450 m while treated with bosentan (70%) or sildenafil were randomized to inhaled treprostinil (up to 54 mug) or inhaled placebo 4 times daily. The primary end point was peak 6MWD at 12 weeks. Secondary end points included time to clinical worsening, Borg Dyspnea Score, NYHA functional class, 12-week trough 6MWD, 6-week peak 6MWD, quality of life, and PAH signs and symptoms. The biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) was assessed.
Twenty-three patients withdrew from the study prematurely (13 treprostinil, 10 placebo). The Hodges-Lehmann between-treatment median difference in change from baseline in peak 6MWD was 19 m at week 6 (p = 0.0001) and 20 m at week 12 (p = 0.0004). Hodges-Lehmann between-treatment median difference in change from baseline in trough 6MWD at week 12 was 14 m (p = 0.0066). Quality of life measures and NT-proBNP improved on active therapy. There were no improvements in other secondary end points, including time to clinical worsening, Borg Dyspnea Score, NYHA functional class, and PAH signs and symptoms. Inhaled treprostinil was safe and well-tolerated.
This trial demonstrates that, among PAH patients who remain symptomatic on bosentan or sildenafil, inhaled treprostinil improves exercise capacity and quality of life and is safe and well-tolerated. (TRIUMPH I: Double Blind Placebo Controlled Clinical Investigation Into the Efficacy and Tolerability of Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension; NCT00147199).
本研究评估了吸入曲前列尼尔在接受波生坦或西地那非治疗的肺动脉高压（PAH）患者中的疗效和安全性。
尽管有有效的治疗方法，但 PAH 仍然无法治愈，预后仍不理想。添加吸入曲前列尼尔，一种长效前列环素类似物，可能是一种安全有效的治疗方法，可作为其他 PAH 特异性口服治疗的附加治疗。
235 名纽约心脏协会（NYHA）功能 III 级（98%）或 IV 级症状和 6 分钟步行距离（6MWD）为 200 至 450m 的 PAH 患者，接受波生坦（70%）或西地那非治疗，随机分为吸入曲前列尼尔（最高 54 mcg）或吸入安慰剂，每日 4 次。主要终点为 12 周时的峰值 6MWD。次要终点包括临床恶化时间、Borg 呼吸困难评分、NYHA 功能分级、12 周时的 6MWD 谷值、6 周时的峰值 6MWD、生活质量和 PAH 体征和症状。评估生物标志物 N 端脑利钠肽前体（NT-proBNP）。
23 名患者提前退出研究（13 名曲前列尼尔，10 名安慰剂）。第 6 周时，治疗组间基线变化的 Hodges-Lehmann 中位数差异在峰值 6MWD 为 19m（p=0.0001），第 12 周时为 20m（p=0.0004）。第 12 周时，治疗组间基线变化的 Hodges-Lehmann 中位数差异在 6MWD 谷值为 14m（p=0.0066）。活性治疗后，生活质量测量和 NT-proBNP 得到改善。其他次要终点，包括临床恶化时间、Borg 呼吸困难评分、NYHA 功能分级和 PAH 体征和症状，均无改善。吸入曲前列尼尔安全且耐受良好。
本试验表明，在接受波生坦或西地那非治疗仍有症状的 PAH 患者中，吸入曲前列尼尔可改善运动能力和生活质量，且安全耐受。（TRIUMPH I：双盲安慰剂对照临床试验，评估吸入曲前列尼尔钠在严重肺动脉高压患者中的疗效和耐受性；NCT00147199）。
