Significant improvement in the control of symptoms related to paroxysmal supraventricular tachycardia (PSVT) is resurrecting etripamil as a self-administered nasal spray a year after it failed to meet the primary endpoint in a phase 3 trial, according to a new analysis from this same study presented at the annual scientific sessions of the American College of Cardiology.
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In the phase 3 NODE-301 trial , presented at the 2020 Heart Rhythm Society annual meeting, etripamil did not show an advantage over placebo at 5 hours for achieving sinus rhythm. Nevertheless, a new presentation of the secondary outcomes suggests substantial clinical benefit.
These advantages include significant reductions in PSVT symptoms, a trend for fewer emergency room visits, and a degree of patient satisfaction that appears meaningful, according to Bruce S. Stambler, MD, an electrophysiologist affiliated with Piedmont Heart Institute, Atlanta.
The data, despite the phase 3 trial results, “support continued development of etripamil nasal spray acute treatment of PSVT,” Dr. Stambler said.
Etripamil is an L-type calcium channel blocker. When administered by nasal spray, it reaches peak effects within about 10 minutes. But the action is short, with a decline in antiarrhythmia effects beginning about 30 minutes after the peak effect.
In the NODE-301 trial, which employed a 2:1 randomization ratio, 138 patients self-administered 70 mg of etripamil or placebo immediately upon experiencing a suspected episode of PSVT.
Up until 45 minutes, the proportion of episodes that converted to sinus rhythm was about 66% greater (hazard ratio, 1.66; P = .02) on etripamil than placebo, but the advantage was then lost. By predefined primary endpoint of 5 hours, when 100% of placebo patients but not all etripamil patients had converted, there was a slight but nonstatistical advantage for placebo (HR 1.08; P = .1212).
However, because of the rapid onset and then the rapid offset of this agent, the 5-hour time point for comparing effects might not have been the optimal duration to compare effects, according to Dr. Stambler.
On the basis of safety of etripamil, which was not associated with any significant adverse events in NODE-301, and the early clinical effect, the investigators have looked again at the data.
For relief of patient-reported symptoms and patient-reported satisfaction, which were secondary endpoints of the study, the data support a clinical role, according to this new analysis.
Specifically, there were large differences on a 7-point scale for all of the measured symptoms of PSVT in favor of etripamil, including rapid pulse (P = .002), palpitations (P = .0001), dizziness (P = 0.01), shortness of breath (P = 0.008), and anxiety (P = 0.006). A numerical advantage for chest pain did not reach significance.
“In general, patients reported scores of 4 to 5 on this scale, which corresponds to ‘not satisfied’ to ‘satisfied,’ while the placebo-treated patients reported scores of 2 to 3, which corresponds to ‘dissatisfied’ or ‘very dissatisfied,’ ” Dr. Stambler reported.
The favorable patient experience is also reflected in the Treatment Satisfaction with Questionnaire for Medication (TSQM-9), which was another NODE-301 endpoint. Evaluated when patients were still blinded to their assigned therapy, the advantage of etripamil over placebo for both global satisfaction (P = .007) and treatment effectiveness (P = .002) were also highly statistically significant.