Intranasal etripamil for rapid treatment of paroxysmal supraventricular tachycardia

Figures & data

Figure 1. Guideline recommended treatment of paroxysmal supraventricular tachycardia and the potential role of etripamil.

Etripamil may be suitable for immediate use in those with good responses, especially in those for whom vagal maneuvers are known to be ineffective. Alternatively, the benefit may be seen after failed vagal maneuvers or in the hospital before intravenous access, which may be obviated if PSVT is terminated by etripamil. Further, etripamil may be useful when IV adenosine has failed to terminate PSVT.

BB: Beta-blocker; CCB: Calcium channel blocker; DCCV: Direct current cardioversion; IV: Intravenous; PIP: Pill-in-the-pocket (e.g., Flecainide); PSVT: Paroxysmal supraventricular tachycardia.

Table 1. Phase 3 studies of etripamil.

Study	Summary of findings	Status	Ref.
NODE-301 Part 1	Etripamil did not outperform placebo for termination of PSVT at 5 h, but significance was suggested for earlier time points. No serious safety concerns were raised	Complete, published	[21]
NODE-302	Open-label extension of NODE-301, confirmed consistent findings and no significant adverse safety signals	Complete, published	[22]
RAPID	Etripamil outperformed placebo for termination of PSVT at 30 min, with significant reductions in patients attending the emergency department or seeking medical attention. No serious safety concerns were raised	Complete, published	[23]
NODE-303	Safety study of etripamil completed in January 2023; results are not yet available	Complete, results awaited	[24]
Open-label extension study	An open-label extension study of NODE 301, 302 and 303 is underway	Ongoing; completion expected April 2024	[25]

Stambler BS, Plat F, Sager PT, et al. First randomized, multicenter, placebo-controlled study of self-administered intranasal etripamil for acute conversion of spontaneous paroxysmal supraventricular tachycardia (NODE-301). Circ. Arrhythm Electrophysiol. 2022;15(12):e010915. doi:10.1161/CIRCEP.122.010915

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Stambler B, Camm AJ, Alings M, et al. Self-administered etripamil for termination of spontaneous paroxysmal supraventricular tachycardia: primary analysis from the RAPID study [Internet]. American Heart Association Scientific Sessions November 2022. 2022. Available from: https://www.acc.org/education-and-meetings/image-and-slide-gallery/~/media/ac4bc002d30f4b6ab0a51996881ff5d0.pdf

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Milestone Pharmaceuticals Inc. Safety study of etripamil nasal spray for patients with paroxysmal supraventricular tachycardia. NODE-303. https://investors.milestonepharma.com/news-releases/news-release-details/milestone-pharmaceuticals-progresses-clinical-and-regulatory

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Milestone Pharmaceuticals Inc. Clinical trials: etripamil nasal spray in patients with paroxysmal supraventricular tachycardia. Available from: https://clinicaltrials.gov/ct2/show/NCT04952610

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