Self-administered nasal spray ‘rapidly’ treats paroxysmal supraventricular tachycardia
CHICAGO — A fast-acting nasal spray safely and effectively converted episodes of paroxysmal supraventricular tachycardia to normal sinus rhythm with a significant reduction in ED utilization and medical intervention, researchers reported.
Etripamil (Milestone Pharmaceuticals), a novel, investigational L-type calcium channel blocker formulated for intranasal spray, is designed to have a rapid onset of action (< 7 minutes) and is short-lasting, James E. Ip, MD, FHRS, associate professor of clinical medicine and clinical cardiac electrophysiologist at Weill Cornell Medicine and New York-Presbyterian Hospital, said during a late-breaking science presentation at the American Heart Association Scientific Sessions.
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“Etripamil has been developed to satisfy an unmet need for self-administered therapy that is convenient and safe outside the health care setting,” Ip said. “It has been shown to be effective at rapidly terminating atrioventricular nodal-dependent paroxysmal supraventricular tachycardia (PSVT).”
As Healio previously reported, the NODE-301 study demonstrated that a single dose of etripamil 70 mg significantly improved PSVT-related symptoms; patient satisfaction and effectiveness of at-home nasal spray therapy for PSVT were higher for etripamil than placebo; and etripamil tended to reduce the need for ED medical interventions for PSVT.
For the phase 3 RAPID study, Ip and colleagues analyzed data from adults with ECG-documented PSVT with episodes lasting at least 20 minutes. Researchers randomly assigned participants to etripamil or placebo spray; treatment regimen was a 70 mg dose, followed by a repeat 70 mg dose after 10 minutes if symptoms persisted. During a perceived PSVT, participants applied an ECG monitor (5-hour recording) and performed a trained vagal maneuver. Primary endpoint was time to termination of adjusted PSVT and conversion to sinus rhythm for at least 30 seconds within 30 minutes of treatment. Secondary endpoints included rates of participants seeking urgent care and rescue treatments received.
Among 692 participants, 255 self-administered etripamil for a perceived PSVT event. Researchers confirmed 184 PSVT events at the time of drug administration.
The probability of conversion to sinus rhythm within 30 minutes was 64.3% with etripamil and 31.2% with placebo, for an HR of 2.62 (95% CI, 1.66-4.15; P < .001).
The rates of conversion of adjudicated PSVT to sinus rhythm at 300 minutes were 82.7% in the PSVT group and 72% in the placebo group (HR = 1.7; 95% CI, 1.213-2.383; P < .001), according to the researchers.
In a prespecified pooled analysis, additional rescue medical interventions were less frequent with etripamil vs. placebo (14.6% vs. 25.4%; P = .013). There were no new safety signals or adverse events with a second dose of etripamil.
Adverse events were mostly mild to moderate and included nasal discomfort (23%), nasal congestion (12.6%) and rhinorrhea (8.9%), all in the etripamil arm.
“These results demonstrate a potential management strategy for patients to self-treat episodes with etripamil in a medically unsupervised setting,” Ip said. “Ongoing analysis of the RAPID open-label period and the NODE-303 trial will provide more insights into the safety and efficacy of etripamil for recurrent episodes of PSVT.”
Discussing the RAPID findings, Julia Indik, MD, PhD, FAHA, professor of medicine, Flinn Foundation and American Heart Association Endowed Chair in Electrophysiology and Heart Disease Research and director of the cardiovascular disease fellowship program at the University of Arizona College of Medicine in Tucson, said the effectiveness of a new drug with rapid onset for at-home, acute treatment for PSVT is an important finding; however, it remains to be seen if such a treatment will be cost-effective.
“By converting people sooner, will [patients] feel that that offsets any discomfort from the nasal congestion? If ultimately FDA-approved, how will this change our approach to SVT management and future SVT guidelines?”
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Ip JE, et al. LBS.08: Treating atrial and supraventricular arrhythmias. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).