麻豆传媒

CHICAGO -- The investigational L-type calcium channel blocker etripamil, formulated as a self-administered nasal spray, shortened spontaneous paroxysmal supraventricular tachycardia episodes among patients in at-home settings, an analysis of the phase III randomized RAPID trial showed.

The probability of the primary endpoint of the study -- conversion of adjudicated paroxysmal supraventricular tachycardia to sinus rhythm within 30 minutes -- was 64.3% with etripamil, which had the option of repeat dosing, compared with 31.2% with placebo (HR 2.62, 95% CI 1.66-4.15, P<0.001), reported James Ip, MD, of Weill Cornell Medical Center in New York City, during the American Heart Association annual meeting.

At 90 minutes, 80.6% of the patients who self-administered etripamil converted to sinus rhythm compared with 60.7% of placebo patients (HR 1.93, 95% CI 1.35-2.75, P<0.001), which was maintained through the 5-hour observation period (82.7% vs 72%). Median time to convert to sinus rhythm was 17.2 minutes with etripamil compared with 53.5 minutes with placebo, Ip noted.

In a prespecified pooled analysis, additional rescue medical interventions were less frequent with etripamil versus placebo (14.6% vs 25.4%, respectively, P=0.013).

"These results demonstrate a potential management strategy to self-treat episodes of paroxysmal supraventricular tachycardia with etripamil in a medically unsupervised setting," Ip said. "Currently, no medications are approved for acute termination of paroxysmal supraventricular tachycardia without direct medical supervision."

RAPID's results reverse the negative 2020 findings from the phase III NODE-301 trial, which tested self-administered etripamil in a similar patient population. That trial, which did not allow for repeat dosing, failed to show a significant benefit for the primary endpoint of conversion over 5 hours compared with placebo.

"Patients do know that they are having supraventricular tachycardia when these episodes occur," Jayne Morgan, MD, of Piedmont Healthcare in Atlanta, told 麻豆传媒. "Generally, these episodes are very worrisome to the patient and will drive the patient to seek medical care."

Aside from symptoms, supraventricular tachycardia can increase risks of blood clotting and downstream strokes.

"This is an extraordinary, groundbreaking study showing the effectiveness of a new drug for home acute treatment," said Julia Indik, MD, PhD, of the University of Arizona College of Medicine in Tuscon. "The number of patients to treat to avoid one emergency room treatment with etripamil is 13."

She pointed out that what is missing from the study is a cost-effectiveness analysis, which will be needed if the drug is approved. It is also unclear how guideline writers will approach the concept of self-administration of this agent, she added.

The double-blind RAPID trial was conducted across approximately 150 sites in the U.S., Europe, and Canada; 255 patients with a history of documented sustained paroxysmal supraventricular tachycardia episodes that lasted at least 20 minutes were randomized to either etripamil (n=135) or placebo (n=120).

Mean patient age was about 54 years, 71% were women, and nearly all were white. Patients had experienced episodes of paroxysmal supraventricular tachycardia for about 2 years before entering the trial.

Treatment consisted of a 70-mg dose of etripamil followed by a second dose after 10 minutes if symptoms persisted, Ip explained. Patients who perceived they were having an episode applied an ECG monitor and performed a previously trained vagal maneuver.

The study was designed to determine results after 180 events were recorded.

As for safety, 50.4% of patients treated with etripamil experienced treatment-emergent adverse events that were mostly mild to moderate and transient, with the most frequent being nasal discomfort (23%), nasal congestion (12.6%), and rhinorrhea (8.9%). No serious cardiac adverse events were observed within 24 hours of etripamil self-administration.

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