NODE-301: Etripamil fails to meet 5-hour supraventricular tachycardia conversion goal
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Etripamil, a novel fast-acting calcium channel blocker administered via nasal spray, was not superior to placebo for conversion of paroxysmal supraventricular tachycardia to sinus rhythm at 5 hours, but bested placebo for short-term conversion, according to results of the NODE-301 trial.
As Healio previously reported, in the NODE-1 phase 2 study, etripamil (Milestone Pharmaceuticals) successfully converted between 65% and 95% of patients with paroxysmal supraventricular tachycardia (PSVT) within 15 minutes, depending on dose. Bruce S. Stambler, MD, FHRS, director of cardiac arrhythmia research and education at Piedmont Heart Institute, Atlanta, presented results of the phase 3 NODE-301 study at the virtual Heart Rhythm Society Annual Scientific Sessions.
“Etripamil, like other calcium channel blockers, slows atrioventricular nodal conduction,” Stambler said during a press conference. “The nasal spray in which it’s formulated is self-administered by patients during PSVT. It has a rapid onset of action and is short acting. Peak effects occur within 5 to 10 minutes, followed by a decline in effects over the next 30 to 45 minutes.”
In an efficacy population of 156 patients (mean age, 55 years; 37% men) with a history of ECG-documented episodes of PSVT of at least 20 minutes, the primary endpoint of time to conversion of an adjudicated PSVT episode up to 5 hours did not differ between those assigned etripamil 70 mg and those assigned placebo (HR = 1.086; 95% CI, 0.726-1.623), Stambler said during the press conference, noting that the 5-hour endpoint was chosen to optimize assessment of safety data.
He said censoring occurred more frequently in the placebo group than the etripamil group; censoring happened when a patient went to the ED for emergency treatment, usually adenosine.
However, he said, etripamil bested placebo in the outcome of time to conversion over 45 minutes (median, 25 minutes vs. 50 minutes; HR = 1.668; 95% CI, 1.026-2.712).
“Early after study drug administration, treatment clearly favored etripamil over placebo, and therefore, based on the drug’s known pharmacology, a post hoc analysis was performed and demonstrated etripamil was significantly more effective than placebo in converting SVT over the first 45 minutes,” Stambler said.
The safety profile of etripamil was favorable, he said, noting that the most common adverse events were nasal discomfort (19.6%) and nasal congestion (8%), which were typically transient and mild.
“These results support continued development of etripamil nasal spray as a self-administered at-home therapy for termination of PSVT,” Stambler said during the press conference. “If successful, etripamil could change the treatment paradigm for acute management of PSVT.”
Etripamil is not yet approved for commercial use in the United States. – by Erik Swain
Reference:
Stambler BS, et al. LBCT01-01. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 6-9, 2020 (virtual meeting).
Disclosures: The trial was funded by Milestone Pharmaceuticals and conducted and coordinated by Medpace. Stambler reports he received honoraria, consultant fees and grants from Milestone Pharmaceuticals.
Perspective
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Wilbur Su, MD
NODE-301 is a clinical evaluation of a fast-acting nasal spray calcium channel blocker medication that may potentially terminate SVT.
Overall, this medication is able to assist in the acute treatment of SVT when other forms of treatment fail. Slow-acting oral medications or techniques such as vagal maneuvers sometimes also work, but this fast-acting medication is novel.
This medication can also only work well in certain subgroups of supraventricular tachycardia, such as the atrioventricular nodal reentry tachycardia or atrioventricular reciprocating tachycardia types. It would not work in other forms of SVT such as ectopic atrial tachycardia and atrial flutter. The prescribing physician may not be able to discern some of the differences between these types of SVT before prescribing, but the risk of trying is low due to the good safety profile.
This trial does demonstrate a good safety profile, with the main limitations being short term and temporizing. Another practical limitation may simply be the cost of the medication.
This medication also only provides temporary relief, as SVT circuit is still there and can recur frequently, even immediately. Curative therapy with ablation is well established and offers definitive therapy.
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