UNASSIGNED: This randomized, double-blind study compared sildenafil at doses of 5, 20, or 80 mg TID in adults with PAH. The primary objective was noninferiority of 80 mg of sildenafil versus 5 mg for all-cause mortality. Secondary end points included time to clinical worsening and change in 6-minute walk distance at 6 months. Interim analyses were planned at 50% and 75% of the anticipated mortality events. Safety and tolerability were assessed in the intention-to-treat population.
UNASSIGNED: The study was halted after the first interim analysis, demonstrating noninferiority for 80 mg of sildenafil versus 5 mg. Of 385 patients enrolled across all dose groups, 78 died. The primary analysis showed a hazard ratio of 0.51 (99.7% CI, 0.22-1.21; P<0.001 for noninferiority) for overall survival comparing 80 mg of sildenafil with 5 mg. Time to clinical worsening favored 80 mg of sildenafil compared with 5 mg (hazard ratio, 0.44 [99.7% CI, 0.22-0.89]; P<0.001). Sildenafil at 80 mg improved 6-minute walk distance from baseline at 6 months compared with 5 mg (least square mean change, 18.9 m [95% CI, 2.99-34.86]; P=0.0201). No significant differences were found between 80 mg of sildenafil and 20 mg in mortality, clinical worsening, and 6-minute walk distance. Adverse event-related drug discontinuations were numerically higher with 80 mg of sildenafil.
UNASSIGNED: Sildenafil at 80 mg was noninferior to sildenafil at 5 mg when examining all-cause mortality in adults with PAH. Secondary efficacy end points favored 80 mg of sildenafil over 5 mg. On the basis of these findings, the Food and Drug Administration recently revoked the approval of 5 mg of sildenafil for adults with PAH, reinforced 20 mg TID as the recommended dose, and now allows dose titration up to 80 mg TID, if needed.
UNASSIGNED: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060487.
■这是随机的,双盲研究比较了西地那非在成人PAH患者中剂量为5,20或80mgTID。主要目标是80mg西地那非对全因死亡率的非劣效性。次要终点包括临床恶化的时间和6个月时6分钟步行距离的变化。计划在50%和75%的预期死亡率事件进行中期分析。在意向治疗人群中评估安全性和耐受性。
■这项研究在第一次中期分析后停止,证明80毫克西地那非与5毫克的非劣效性。在所有剂量组的385名患者中,78人死亡主要分析显示,与80mg西地那非和5mg相比,总生存率的风险比为0.51(99.7%CI,0.22-1.21;非劣效性P<0.001)。与5mg相比,80mg西地那非的临床恶化时间更受欢迎(风险比,0.44[99.7%CI,0.22-0.89];P<0.001)。与5mg相比,西地那非80mg在6个月时改善了基线的6分钟步行距离(最小平方均值变化,18.9m[95%CI,2.99-34.86];P=0.0201)。80毫克西地那非和20毫克之间的死亡率没有显着差异。临床恶化,和6分钟的步行距离。80mg西地那非的不良事件相关药物停药的数量更高。
■在检查PAH成人的全因死亡率时,80mg的西地那非不劣于5mg的西地那非。次要疗效终点有利于80mg西地那非超过5mg。根据这些发现,美国食品和药物管理局最近撤销了用于成人PAH的5mg西地那非的批准,强化20mgTID作为推荐剂量,现在允许剂量滴定高达80毫克TID,如果需要。
■URL:https://www。clinicaltrials.gov;唯一标识符:NCT02060487.