Doubling the dose of self-administered etripamil terminates PSVT

Self-administered etripamil was safe and terminated paroxysmal supraventricular tachycardia (PSVT) more frequently than placebo, the primary analysis of the phase 3 RAPID Study (NODE-301 part 2) demonstrated.

The novel investigational L-type calcium channel blocker etripamil, formulated for intranasal spray, delivered a rapid conversion of PSVT to normal sinus rhythm in the phase 2 NODE-1 trial (NCT02296190) [1]. The current phase 3 RAPID study (NODE-301 – Part 2, NCT03464019) randomised 692 participants with an ECG-documented diagnosis of PSVT 1:1 to etripamil or placebo in an at-home treatment setting [2]. After participants recognised symptoms they applied cardiac monitoring, attempted a vagal manoeuvre, and administered the study drug (etripamil 70 mg) or placebo. If symptoms persisted for 10 minutes, a second, equal drug dose was self-administered. The primary endpoint was PSVT conversion to sinus rhythm over 30 minutes. At the current data cut point of the RAPID study, 255 patients had been treated for PSVT, making up the safety population, and 184 patients had verified PSVT and had been treated for it, comprising the efficacy population. Dr James Ip (Weill Cornell Medicine, NY, USA) presented the primary results of the study.

At 30 minutes, 64.3% of the patients in the etripamil arm had converted from PSVT to a normal sinus rhythm compared with 31.2% of the patients in the placebo arm (HR 2.62; 95% CI 1.66–4.15; P<0.001). The observed difference in conversion rates between the 2 arms remained significant at 300 minutes (82.7% vs 72.0%; HR 1.70; P<0.001, etripamil vs placebo). The median time to conversion from PSVT to a normal sinus rhythm was 17.2 minutes in the etripamil and 53.5 minutes in the placebo arm (see Figure). These results were consistent across subgroups.

 

Figure: Median time to conversion from PSVT to normal sinus rhythm per treatment group [1]

 

This being the first study in which a second dose of etripamil was tested, no new safety issues were reported, according to Dr Ip. “Importantly, no cases of second-degree or third-degree atrioventricular block were reported.” The rate of treatment-related adverse events (AEs) was higher in the etripamil (50.4%) than in the placebo arm (16.7%), but no serious AEs were observed. The most commonly observed AEs in the etripamil arm were nasal discomfort (23.0%), nasal congestion (12.6%), and rhinorrhoea (8.9%).

Dr Julia Indik (University of Arizona, AZ, USA) congratulated Dr Ip on the results of the RAPID Study but mentioned that the cost-effectiveness of this approach needs to be determined. “What is the number-needed-to-treat to avoid an emergency room visit, and will this balance out the cost of self-administered therapy? Also, we need to investigate patient satisfaction concerning the nasal adverse symptoms that are associated with etripamil.”

1. 1. Stambler BS, et al. JACC. 2018;72(5):489–497.
   2. Stambler BS, et al. Self-administered etripamil for termination of spontaneous paroxysmal supraventricular tachycardia: Primary analysis from The RAPID study. LBS.08, AHA Scientific Sessions 2022, 05–07 November, Chicago, USA.

 

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Posted on 11 January, 2023