In the RAPID trial, administration of the calcium-channel blocker etripamil intranasally using a symptom-prompted, self-administered, initial and optional-repeat-dosing regimen “was well tolerated, safe, and superior to placebo for the rapid conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm,” researchers report. “This approach could empower patients to treat paroxysmal supraventricular tachycardia themselves outside of a health-care setting, and has the potential to reduce the need for additional medical interventions, such as intravenous medications given in an acute-care setting.”
Participants were adults in part 2 of the NODE-301 study conducted at 160 sites in North America and Europe. All had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes (≥20 min). Following 2 test doses of etripamil, participants tolerating the drug were randomized to self-administered intranasal etripamil 70 mg or placebo with repeat doses of symptoms persisting beyond 10 min. The primary endpoint was time to conversion of paroxysmal supraventricular tachycardia to sinus rhythm for at least 30 s within 30 min after the first dose.
“Between Oct 13, 2020, and July 20, 2022, among 692 patients randomly assigned, 184 (99 from the etripamil group and 85 from the placebo group) self-administered study drug for atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia, with diagnosis and timing confirmed,” the authors write. “Kaplan-Meier estimates of conversion rates by 30 min were 64% (63/99) with etripamil and 31% (26/85) with placebo (hazard ratio 2.62; 95% CI 1.66–4.15; P <0.0001). Median time to conversion was 17.2 min (95% CI 13.4–26.5) with the etripamil regimen versus 53.5 min (38.7–87.3) with placebo. Prespecified sensitivity analyses of the primary assessment were conducted to test robustness, yielding supporting results. Treatment-emergent adverse events occurred in 68 (50%) of 99 patients treated with etripamil and 12 (11%) of 85 patients in the placebo group, most of which were located at the administration site and were mild or moderate, and all of which were transient and resolved without intervention. Adverse events occurring in at least 5% of patients treated with etripamil were nasal discomfort (23%), nasal congestion (13%), and rhinorrhea (9%). No serious etripamil-related adverse events or deaths were reported.”