Etripamil nasal spray rapidly terminated induced SVT with a high conversion rate. The safety and efficacy results of this study provide guidance for etripamil dose selection for future studies involving self-administration of this new intranasal calcium-channel blocker in a real-world setting for the termination of SVT. (Efficacy and Safety of Intranasal MSP-2017 [Etripamil] for the Conversion of PSVT to Sinus Rhythm [NODE-1]; NCT02296190).

Background: 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. Methods: 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. Results: 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. Conclusions: 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. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03464019.

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Summary:The use of serum reverse T, (rT,) levels in the assessment of amiodarone efficacy is controversial. We prospectively studied 10 patients with frequent ventricular ectopy and symptomatic ventricular tachycardia (VT) treated with amiodarone. Serial 24-h Holter monitor, thyroid function studies including serum rT,, and 12-lead electrocardiogram were performed on each patient at baseline, and at 1,4, 12, and 24 weeks of oral amiodarone therapy. Serial Holter monitors on therapy were analyzed for 100% suppression of VT, 90% suppression of couplets, and 85 % suppression of ventricular ectopic beats (VEBs) compared with baseline Holter, defining patient groups VT-, Co-, and VEB-, respectively. Lack of arrhythmia suppression to this degree defined groups as VT + , Co + , and VEB + . There were no statistically significant differences in rT, levels between VT + and VTgroups, Co + and Co -groups, or the VEB + and VEBgroups. VT suppression could not be predicted at any rT, level. We conclude that serum rT, is an insensitive means of assessing amiodarone efficacy.