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The trial achieved its primary efficacy endpoint of terminating PSVT with self-administered etripamil, using symptom-based optional repeat dosing.
New findings indicate etripamil demonstrated clinical efficacy and favorable safety and tolerability in the RAPID trial in patients experiencing a paroxysmal supraventricular tachycardia (PSVT) event.
The trial met its primary efficacy endpoint of terminating PSVT with self-administered etripamil, using symptom-based optional repeat dosing.
The data was presented in a late-breaking session at the American Heart Association Scientific Sessions 2022 in Chicago.
“Results demonstrate a potential management strategy for patients to self-treat episodes with etripamil in a medically unsupervised setting,” said James E. Ip, MD, Associate Professor of Clinical Medicine, Weill Cornell Medical College. “Ongoing analysis of RAPID open-label period and NODE-303 trial will provide more insights into the safety and efficacy of etripamil for recurrent episodes of PSVT.”
There are no current medications approved for acute termination of PSVT without direct medical supervision. The medication etripamil is a novel, investigational, L-type calcium channel blocker formulated for intranasal spray with rapid onset of action (≤7 minutes). It is short-lasting and inactivated by blood esterases. It was developed to treat atrioventricular nodal-dependent PSVT and to fulfill an unmet need for self-administered therapy that is considered both convenient and safe outside of a healthcare setting.
The RAPID study is a randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy and safety of etripamil in patients experiencing a PSVT episode in an at-home setting. The trial was conducted in approximately 150 sites in the United States, Europe, and Canada.
Following open-label etripamil test doses (2 x 70-mg, 10 minutes apart), the included patients (18 years or older) with a history of documented PSVT and sustained episodes lasting 20 minutes or longer were randomized 1:1 to etripamil or placebo. The treatment regimen was a 70-mg dose followed by a repeat 70-mg dosage if a patient’s symptoms persisted after 10 minutes.
In the case of an at-home treated PSVT episode, patients applied an electrocardiogram (ECG) monitor for a 5-hour recording and performed a previously taught vagal maneuver. If the vagal maneuver was unsuccessful, a patient would then self-administer the randomized treatment.
The primary study endpoint was the time-to-termination of adjudicated PSVT and conversion to sinus rhythm for ≥30 seconds within 30 minutes of treatment. Secondary endpoints included the rate of patients seeking urgent care and rescue treatments received. The study concluded when there were 180 confirmed PSVT events.
The overall safety population included 706 patients who received the test dose, of which 692 (98%) were randomized. A total of 34 patients were randomized to single-dose regimen in NODE-301 Part 1 trial and 658 were randomized to optional repeat-dose regimen in RAPID.
Moreover, a total of 255 patients self-administered the study drug regimen for a perceived PSVT event, with 34 receiving a single-dose drug regimen and 221 receiving an optional repeat-dose regimen.
Investigators noted all ECG tracings were independently and blindly adjudicated. Adjudication confirmed 184 PSVT events, as well as the time of drug administration and of PSVT termination. The data show the probability of conversion to SR within 30 minutes was 64.3% with etripamil and 31.2% with placebo (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.66 - 4.15; P <.001).
Additionally, at the 300-minute endpoint, the conversion of adjudicated PSVT to NSR was 82.7% with etripamil and 72.0% for placebo (HR, 1.70; 95% CI, 1.213 - 2.383); P < .001). In a prespecified pool analysis, investigators found additional rescue and medical interventions were less frequent with etripamil versus placebo (14.6% vs 25.4%; P = .013).
The safety data show 68 (50.4%) patients treated with etripamil had treatment-emergency adverse events, considered mostly mild-to-moderate and transient. The most frequent were nasal discomfort (23%), nasal congestion (12.6%), and rhinorrhea (8.9%), with no serious cardiac safety events observed within 24 hours of etripamil.
“Self-Administered Etripamil for Termination of Spontaneous Paroxysmal Supraventricular Tachycardia: Primary Analysis From the RAPID Study,” was presented at AHA 2022.