A significant improvement in the control of symptoms related to paroxysmal supraventricular tachycardia (PSVT) is resurrecting etripamil as a self-administered nasal spray one year after not meeting the primary endpoint in a phase 3 trial, according to a new analysis of this same study. presented at the annual scientific sessions of the American College of Cardiology.
In phase 3 Test NODE-301, presented at the Heart Rhythm Society 2020 annual meeting, etripamil showed no advantage over placebo at 5 hours to achieve sinus rhythm. However, a new presentation of secondary outcomes suggests a substantial clinical benefit.
These benefits include significant reductions in PSVT symptoms, a trend toward fewer emergency room visits, and a degree of patient satisfaction that appears significant, according to Bruce S. Stambler, MD, an electrophysiologist affiliated with the Piedmont Heart Institute, Atlanta.
The data, despite the results of the phase 3 trial, “support the continued development of acute nasal spray treatment of etripamil from PSVT,” Dr. Stambler.
Etripamil is an L-type calcium channel blocker. When administered with nasal spray, it achieves its maximum effects after about 10 minutes. But the action is short, with a decrease in antiarrhythmic effects that begins about 30 minutes after the maximum effect.
In the NODE-301 trial, which used a 2: 1 randomization ratio, 138 patients self-administered 70 mg of etripamil or placebo immediately after experiencing a suspicious episode of PSVT.
Up to 45 minutes, the proportion of episodes that converted to sinus rhythm was approximately 66% higher (risk ratio, 1.66; P = 0.02) in etripamil than in placebo, but the advantage was he lost. By a 5-hour predefined primary endpoint, when 100% of placebo patients but not all etripamil patients had converted, there was a slight but non-statistical advantage for placebo (HR 1.08; P = 0.1212 ).
However, due to the rapid onset and after rapid compensation of this agent, the 5-hour time point for comparing effects might not have been the optimal time to compare effects, according to Drs. Stambler.
Based on the safety of etripamil, which was not associated with any significant adverse events in NODE-301, and the initial clinical effect, the researchers re-examined the data.
According to this new analysis, the data support a clinical role in relieving patient-reported symptoms and patient-reported satisfaction, which were secondary objectives of the study.
Specifically, there were large differences on a 7-point scale for all measured symptoms of PSVT in favor of etripamil, including rapid pulse (P = .002), palpitations (P = .0001), dizziness (P = .000). 0.01), shortness of breath (P = 0.008) and anxiety (P = 0.006). A numerical advantage for chest pain did not reach its importance.
In general, patients reported scores of 4 to 5 on this scale, which ranged from “dissatisfied” to “satisfied,” while patients treated with placebo reported scores of 2 to 3, corresponding to “dissatisfied.” or “very dissatisfied,” Dr. Stambler reported.
Favorable patient experience is also reflected in Treatment Satisfaction with the Medication Questionnaire (TSQM-9), which was another NODE-301 endpoint. Assessed when patients were not yet blinded with assigned therapy, the advantage of etripamil over placebo for both overall satisfaction (P = 0.007) and treatment efficacy (P = 0.002) was also highly statistically significant.
The subjective experience of the patients seemed to be reflected in objective measures. When the two groups for emergency interventions were compared, the need was reduced by about half (12.1% vs. 24.5%; P = 0.051) among those treated with etripamil. While this was only lacking in the conventional measure of statistical significance, it was close. Similarly, patients randomized to etripamil needed fewer rescue medications (14.0% vs. 26.5%; P = 0.059).
According to Dr. Stambler, adenosine was the most common of the rescue medications. He said there was no difference between the groups in the use of rescue oral therapies.
Comparing etripamil and placebo in the subgroup that visited an emergency room for PSVT, there was a delay in emergency visits among those who were randomized to etripamil (116 vs. 79 minutes; P <0, 05), suggesting that this agent reduced the sense of urgency. when PSVT symptoms develop, according to Dr. Stambler.
On average, patients who enrolled in this trial had a history of PSVT of about 1.5 years. The year before enrollment, the average number of emergency room visits was about nine.
In the trial design, patients had to take a test dose of etripamil under the observation of a doctor before sending them home with the assigned therapy, but Dr. Stambler did not believe the requirement, if any. the drug is approved, be labeled.
Unexpectedly, many patients had relief from symptoms even without converting to sinus rhythm, Dr. Stambler acknowledged. He speculated that the reduction in heart rate associated with etripamil may have provided sufficient symptom relief to relieve anxiety, producing the relative benefit for patient satisfaction.
Jodie L. Hurwitz, MD, director of the electrophysiology lab at Dallas Medical City Hospital, indicated that new options are needed for PSVT. An expert panelist during the session where this data was presented, was especially interested in the rapid relief of symptoms.
“It would be great to have a therapy that could be self-administered at home. Patients would like it too,” he said.
Mary N. Walsh, MD, a heart failure specialist affiliated with Indiana University in Indianapolis, sees a potential role for a self-administered therapy such as etripamil along with portable devices. He noted that the proportion of patients using these devices to control arrhythmias is increasing, providing a role for easily transportable therapy that could be used quickly when symptoms develop.
However, after the negative phase 3 test, more data now needs to be collected to assure regulatory authorities that this agent is safe and effective. Dr. Stambler said the developer is now committed to continuing these studies.
Dr. Stambler has a financial relationship with Milestone Pharmaceuticals, which develops etripamil nasal spray and was the sponsor of this trial. Walsh and Hurwitz have no relevant conflicts of interest.
This article originally appeared on MDedge.com, which is part of the Medscape professional network.