By Dr Jonathan Shurlock
Edited by Dr Saadia Aslam
Etripamil is a rapid-acting, intranasally administered calcium channel blocker. Previously, the NODE-301 study found it to be safe and well tolerated but without demonstrable benefit compared with placebo, as a single-dose treatment. Further, post-hoc analysis of the NODE-301 trial demonstrated some, time from dose-dependent benefit.
Led by Dr Bruce Stambler, the RAPID trial is a multi-centre, placebo-controlled, randomised trial. Participants ≥18 years old, with a history of symptomatic (lasting for ≥20 minutes) paroxysmal SVT and documented ECG evidence were eligible. Patients with ECG evidence of pre-excitation, second or third-degree AV block, or ventricular arrhythmia were excluded.
Participants (n=692) who tolerated two test doses of intranasal etripamil (70 mg, 10 min apart) whilst in sinus rhythm were randomised on a 1:1 basis to receive either etripamil (n=99) or placebo (n=85). Participants were trained to attach continuous ECG monitoring at the onset of symptoms followed by self-administration of treatment. If symptoms persisted beyond 10 minutes, participants were instructed to self-administer a second dose. Continuous ECG monitoring data was assessed for the primary outcome measure of time to conversion of paroxysmal SVT to sinus rhythm by blinded observers.
At 30 minutes post-administration rates of conversion were higher in the etripamil group compared with placebo (64% versus 31%, respectively, hazard ratio 2.62; 95% CI 1.66–4.15; p<0·0001). Median time to conversion was faster in the etripamil group when compared with placebo (17.2 min versus 53.5 min, respectively).
Adverse events, include mild or moderate transient effects (nasal discomfort, nasal congestion and rhinorrhea) at the administration site that did not require intervention, were higher in the etripamil group (50%) compared with 11% in the placebo group.
In the context of immediate self-administration and the additional second dose, compared to NODE-301, the RAPID trial has demonstrated etripamil to be safe and superior to placebo in the rapid conversion of SVT to sinus rhythm. The potential benefits include reduced emergency presentations and hospitalisations whilst empowering patients and improving engagement with their healthcare. Future directions should involve a direct comparison with other ‘pill-in-pocket’.
The full study can be found here: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00776-6/fulltext#%20
