Intranasal etripamil safe, effective for conversion of Paroxysmal supraventricular tachycardia to sinus rhythm

A new study published in The Lancet suggests that for the treatment of atrioventricular nodal-dependent paroxysmal supraventricular tachycardia (PSVT), intranasal etripamil is secure and efficient, and its usage in the community may be justified.

Etripamil is a fast-acting, intranasally delivered calcium-channel blocker under development for on-demand therapy for paroxysmal supraventricular tachycardia outside of a health-care setting. As a result, Bruce Stambler and colleagues conducted this study to assess the efficacy and safety of etripamil 70 mg nasal spray in the treatment of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 minutes using a symptom-prompted, repeat-dose regimen.

As part of the NODE-301 investigation, RAPID was a multicenter, randomised, placebo-controlled, event-driven experiment that was undertaken at 160 locations across North America and Europe. Eligible patients were at least 18 years old and had a history of paroxysmal supraventricular tachycardia with prolonged, symptomatic episodes lasting at least 20 minutes, as verified by an ECG. During sinus rhythm, patients were given two test doses of intranasal etripamil (each 70 mg, 10 minutes apart); those who tolerated the test doses were randomly assigned (1:1) to receive either etripamil or placebo utilizing an interactive response technology system. Patients self-administered an initial dosage of intranasal 70 mg etripamil or placebo after experiencing signs of paroxysmal supraventricular tachycardia, and a repeat dose of symptoms persisted for more than 10 minutes.

All patients who received blinded study medication for a confirmed atrioventricular-nodal-dependent event were included in the analysis of continuously recorded electrocardiographic data for the primary endpoint of time to conversion of paroxysmal supraventricular tachycardia to sinus rhythm for at least 30 s within 30 min after the first dose. All patients who self-administered a blinded study medicine for a reported paroxysmal supraventricular tachycardia episode had their safety outcomes evaluated.

The key findings of this study were:

1. In 184 of the 692 randomly assigned patients between October 13, 2020 and July 20, 2022, with diagnosis and timing confirmed, 184 (99 from the etripamil group and 85 from the placebo group) self-administered study medication for atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia.

2. The estimated conversion rates by 30 min according to Kaplan-Meier were 64% (63/99) with etripamil and 31% (26/85) for placebo (hazard ratio: 2; 95% confidence interval: 1;66-4;15; p=0.0001).

3. With the etripamil regimen, the median time to conversion was 17 2 min (95% CI 13 4–26 5), while with the placebo, it was 53 5 min (38 8–77 3).

4. To verify the robustness, predetermined sensitivity analyses of the primary assessment were performed; the results were encouraging.

5. 68 (50%) of the 99 patients given etripamil experienced treatment-emergent adverse events, as did 12 (11%) of the 85 patients given a placebo.

6. The majority of these mild to moderate adverse events, which were all temporary and self-limited, occurred at the administration site.

7. Nasal discomfort (23%), nasal congestion (13%), and rhinorrhea (9%) were adverse events that happened in at least 5% of patients receiving etripamil treatment.

8. No fatalities or major adverse events connected to etripamil were reported.

Reference: 

Stambler, B. S., Camm, A. J., Alings, M., Dorian, P., Heidbuchel, H., Houtgraaf, J., Kowey, P. R., Merino, J. L., Mondésert, B., Piccini, J. P., Pokorney, S. D., Sager, P. T., Verma, A., Shardonofsky, S., Chen, M., Ip, J. E., … Al-Zoebi, A. (2023). Self-administered intranasal etripamil using a symptom-prompted, repeat-dose regimen for atrioventricular-nodal-dependent supraventricular tachycardia (RAPID): a multicentre, randomised trial. In The Lancet. Elsevier BV. https://doi.org/10.1016/s0140-6736(23)00776-6