NODE-301: Etripamil fails to meet 5-hour supraventricular tachycardia conversion goal
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
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.