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NODE-1: Etripamil may halt supraventricular tachycardia
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Etripamil, a novel fast-acting calcium channel blocker administered via nasal spray, quickly terminated supraventricular tachycardia, according to the results of the NODE-1 trial.
Researchers performed a phase 2 study during electrophysiological testing of 104 patients (median age, 55 years; 57% women) with supraventricular tachycardia who were induced into supraventricular tachycardia before catheter ablation. Patients were randomly assigned to placebo or one of four doses — 35 mg, 70 mg, 105 mg or 140 mg — of etripamil (Milestone Pharmaceuticals) after 5 minutes in supraventricular tachycardia.
The primary endpoint was rate of conversion from supraventricular tachycardia to sinus rhythm within 15 minutes of drug administration. Secondary endpoints included time to conversion and adverse events.
Conversion to sinus rhythm
According to the researchers, the primary endpoint was achieved in 65% of the 35-mg etripamil group, 87% of the 70-mg etripamil group, 75% of the 105-mg etripamil group and 95% of the 140-mg etripamil group, compared with 35% for the placebo group (OR for 140 mg etripamil vs. placebo = 37.14; 95% CI, 3.84-1,654.17; OR for 105 mg etripamil vs. placebo = 5.57; 95% CI, 1.19-27.63; OR for 70 mg etripamil vs. placebo = 12.38; 95% CI, 2.28-82.26; P < .0001 for trend).
Among those who converted to sinus rhythm, median time to conversion was less than 3 minutes, Bruce S. Stambler, MD, from Piedmont Heart Institute, and colleagues wrote.
Most adverse events were related to the nasal route of administration or local irritation, and three patients had serious adverse events possibly related to etripamil. There were no deaths or drug discontinuations due to adverse events, the researchers wrote.
Systolic BP did not significantly decrease in the placebo, 35-mg etripamil or 70-mg etripamil groups. In the 105-mg etripamil group, there was a maximum statistically significant decrease of 17 mm Hg 6 minutes after dosing, and in the 140-mg group, there was a maximum statistically significant decrease of 20 mm Hg 6 minutes after dosing, Stambler and colleagues wrote.
“From an efficacy standpoint, [the results make] this intranasal calcium channel blocker an excellent drug candidate to fill the existing gap in therapy for the rapid termination of [supraventricular tachycardia] outside of the health care setting,” the researchers wrote.
Potential benefits
“Keeping patients away from the emergency department or unnecessary chronic antiarrhythmic therapy or ablation procedures for infrequent attacks will be the biggest benefit of this therapy,” Gerald V. Naccarelli, MD, from the electrophysiology program at Penn State University Heart and Vascular Institute, Penn State University College of Medicine, The Milton S. Hershey Medical Center in Hershey, Pennsylvania, and colleagues wrote in a related editorial. “Defining the right patient population and the most efficacious and safe dose will be an important part of clinical trials. Given the transient circulation of the drug, long-term adverse effects will be unlikely and of little concern to the regulatory bodies.”
Etripamil is not yet approved for use in the United States. – by Erik Swain
Disclosures: The study was funded by Milestone Pharmaceuticals. Naccarelli reports he has consulted for GlaxoSmithKline, Janssen and Omericos and received a research grant from Janssen. Stambler reports no relevant financial disclosures. Please see the study and editorial for the other authors’ relevant financial disclosures.
Perspective
Back to TopMark Link, MD
This is the first study that I am aware of that demonstrates potential of an intranasal treatment for supraventricular tachycardia. If approved, this would be a niche product for people that do not want ablations or have very rare episodes. I can see there being clinical applicability here.
The biggest potential benefit is that patients could treat their supraventricular tachycardia episodes without going to the ED. The biggest potential risk is that this is a calcium-channel blocker, an antihypertensive agent, so drops in BP can occur, which was seen in this study, especially at the highest dose.
The company is planning a phase 3 clinical trial, which they will need to conduct to get FDA approval. We need to see how this works out in the community rather than in the electrophysiology lab.
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