Intranasal Etripamil for Spontaneous Paroxysmal Supraventricular Tachycardia

Patients with spontaneous symptomatic paroxysmal supraventricular tachycardia may benefit from self-administered, intranasal etripamil.

The potential utility of self-administered intranasal etripamil for spontaneous symptomatic paroxysmal supraventricular tachycardia (PSVT) has been reported in a medical unsupervised setting, according to findings published in the journal Circulation: Arrhythmia and Electrophysiology.

The investigators sought to evaluate the efficacy and safety of etripamil nasal spray when self-administered in patients with symptomatic, sustained PSVT. Intranasal etripamil is an investigational, fast-acting, nondihydropyridine, L-type calcium channel blocker that has been designed for unsupervised self-administration, in order to terminate atrioventricular nodal–dependent PSVT.

They conducted the phase 3, multicenter, double-blind, placebo-controlled NODE-301 study ( Identifier: NCT03464019). In the study, following a medically supervised etripamil test dose that was administered to individuals while they were in sinus rhythm, participants were randomly assigned in a 2:1 ratio to treatment with etripamil 70 mg or placebo. When symptoms of PSVT developed, participants applied a cardiac monitor and attempted the use of a vagal maneuver. If their symptoms continued, they self-administered a blinded treatment of either etripamil or placebo. Continuous electrocardiogram (ECG) readings were reviewed by an independent adjudication committee.

The primary efficacy endpoint of the study was termination of PSVT within 5 hours of administration of the study drug. The study population comprised individuals aged 18 years or older with ECG documentation of prior PSVT and a history of episodes that typically lasted for approximately 20 minutes or longer.

These findings support the ongoing clinical development of etripamil nasal spray for patient-actuated, on-demand, acute treatment of PSVT outside a health care environment.

There were a total of 156 positive PSVT events that were treated with etripamil (n=107) or placebo (n=49). Results of the study showed that the hazard ratio (HR) for the primary outcome of time-to-conversion to sinus rhythm during the 5-hour observation period was 1.086 (95% CI, 0.726-1.623; P =.12).

Based on predefined sensitivity analyses, the effects of etripamil, compared with  placebo, occurred at 3, 5, 10, 20, and 30 minutes (P <.05). Despite not meeting the primary efficacy endpoint, evidence of an early treatment effect was demonstrated, which persisted through 30 minutes to approximately 60 minutes, compared with placebo. At 30 minutes, there was 53.7% of SVT conversion in the etripamil group, compared with 34.7% in the placebo group (HR, 1.87; 95% CI, 1.09-3.22; P =.02).

Treatment with etripamil was shown to be well tolerated, with a majority of adverse events limited to the administration site, and considered mild and transient. Adverse events that were reported in the etripamil and placebo treatment arms included nasal discomfort, nasal congestion, and oropharyngeal pain.

Some limitations of the study include the broad range of participant ages in the study, which likely reflects the known difficulties involved in recruiting participants for the 18- to 30-year-old age-group. Further, the lack of a specific time when the study drug should be taken after PSVT initiation might influence the conversion rate and the time to conversion in each group.

The authors wrote, “These findings support the ongoing clinical development of etripamil nasal spray for patient-actuated, on-demand, acute treatment of PSVT outside a health care environment.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


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. Published online November 28, 2022. doi: 10.1161/CIRCEP.122.010915