背景:药物终止阵发性室上性心动过速(PSVT)通常需要医学监督干预。鼻内依替帕米,是一项研究快速行动,非二氢吡啶,L型钙通道阻滞剂,设计用于无监督的自我管理以终止房室结依赖性PSVT。2期结果显示,在104例PSVT患者中,依替帕米的潜在安全性和有效性。
方法:NODE-301,第三阶段,多中心,双盲,安慰剂对照研究评估了依替帕米鼻喷雾剂的疗效和安全性,有症状的持续PSVT患者无监督。在窦性心律期间接受医学监督的依替帕米试验剂量后,患者以2:1的比例随机分配接受依替帕米70mg或安慰剂.当PSVT症状出现时,患者使用心脏监护仪并尝试迷走神经动作;如果症状持续存在,他们自己进行盲化治疗。一个独立的裁决委员会审查了连续的心电图记录。主要疗效终点是在研究药物给药后5小时内终止裁定的PSVT。
结果:NODE-301在接受依替帕米(n=107)或安慰剂(n=49)的治疗中发现156例PSVT事件。主要终点的危险比,在5小时的观察期间转换为窦性心律的时间,为1.086(95%CI,0.726-1.523;P=0.12)。在预定义的灵敏度分析中,在3,5,10,20和30分钟时(P<0.05)出现了依替帕米效应(与安慰剂相比).例如,30分钟后,与安慰剂组的34.7%相比,治疗组的SVT转化率为53.7%(风险比,1.87[95%CI,1.09-3.22];P=0.02)。Etripamil耐受性良好;不良事件主要与短暂的鼻部不适和充血有关(19.6%和8.0%,分别,随机治疗引起的不良事件。
结论:尽管未达到主要的5小时疗效终点,在较早时间点的分析显示,在终止PSVT方面有依替帕米治疗效果.PSVT期间的依曲帕米自我给药是安全且耐受性良好的。这些结果支持在医学无人监督的情况下,在PSVT期间自我给药的依替帕米鼻喷雾剂的持续临床开发。
背景:URL:https://www。
结果:gov;唯一标识符:NCT03464019。
Pharmacologic termination of paroxysmal supraventricular tachycardia (PSVT) often requires medically supervised intervention. Intranasal etripamil, is an investigational fast-acting, nondihydropyridine, L-type calcium channel blocker, designed for unsupervised self-administration to terminate atrioventricular nodal-dependent PSVT. Phase 2 results showed potential safety and efficacy of etripamil in 104 patients with PSVT.
NODE-301, a phase 3, multicenter, double-blind, placebo-controlled
study evaluated the efficacy and safety of etripamil nasal spray administered, unsupervised in patients with symptomatic sustained PSVT. After a medically supervised etripamil test dose while in sinus rhythm, patients were randomized 2:1 to receive etripamil 70 mg or placebo. When PSVT symptoms developed, patients applied a cardiac monitor and attempted a vagal maneuver; if symptoms persisted, they self-administered blinded treatment. An independent Adjudication Committee reviewed continuous electrocardiogram recordings. The primary efficacy endpoint was termination of adjudicated PSVT within 5 hours after
study drug administration.
NODE-301 accrued 156 positively adjudicated PSVT events treated with etripamil (n=107) or placebo (n=49). The hazard ratio for the primary endpoint, time-to-conversion to sinus rhythm during the 5-hour observation period, was 1.086 (95% CI, 0.726-1.623; P=0.12). In predefined sensitivity analyses, etripamil effects (compared with placebo) occurred at 3, 5, 10, 20, and 30 minutes (P<0.05). For example, at 30 minutes, there was a 53.7% of SVT conversion in the treatment arm compared to 34.7% in the placebo arm (hazard ratio, 1.87 [95% CI, 1.09-3.22]; P=0.02). Etripamil was well tolerated; adverse events were mainly related to transient nasal discomfort and congestion (19.6% and 8.0%, respectively, of randomized treatment-emergent adverse events.
Although the primary 5-hour efficacy endpoint was not met, analyses at earlier time points indicated an etripamil treatment effect in terminating PSVT. Etripamil self-administration during PSVT was safe and well tolerated. These results support continued clinical development of etripamil nasal spray for self-administration during PSVT in a medically unsupervised setting.
URL: https://www.
gov; Unique identifier: NCT03464019.