People who experience paroxysmal supraventricular tachycardia can use a simple treatment without medical supervision, according to a new study published in the Journal of the American Heart Association.
Research Highlights:
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Etripamyl Nasal Spray for Conversion of Repeated Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia During Long-Term Follow-Up: Results from the NODE-302 Study
There are currently no medications approved for acute termination of paroxysmal supraventricular tachycardia (PSVT) without direct medical supervision. Calcium channel blockers (CCBs), beta blockers (BBs), and adenosine are effective treatments for acute PSVT, but these medications require intravenous administration for rapid termination, because their oral formulations have a delayed onset of action due to its inconsistent and prolonged rates of absorption and first-pass metabolism. Although some patients may self-administer oral BBs or CCBs acutely to control their recurrent episodes of PSVT, limited evidence supports the efficacy and safety of this pocket pill (PIP) approach for sustained, symptomatic PSVT.
Etripamil is a non-dihydropyridine , L-type calcium channel blocker (CCB) developed to enable patients to rapidly self-terminate their atrioventricular node-dependent PSVT episodes using a nasal spray. In the first-in-human single ascending dose Phase 1 study, 72 healthy adults received etripamil at doses of 3.5, 7, 14, 30, 60, 105, and 140 mg. In phase 2, a randomized, double-blind NODE-1 study (multicenter, placebo-controlled, dose-ranging phase 2 electrophysiology study of intranasal administration of MSP-2017 for conversion of induced paroxysmal supraventricular tachycardia to sinus rhythm) (NCT02296190), 104 patients were randomly chosen to receive placebo or etripamil (with doses ranging from 35 to 140 mg) during episodes of PSVT induced in an electrophysiology laboratory.
Findings from phase 1 and 2 studies suggested that etripamil nasal spray was rapidly absorbed through the nasal mucosa with a dose-dependent time to maximum concentration of 5 to 8.5 minutes at doses ≥14 mg. Treatment with etripamil appeared to be well tolerated and most adverse events (AEs) were associated with the nasal route of administration (e.g., nasal congestion, lacrimation, nasal discomfort, and rhinorrhea). Based on the results of the phase 1 and 2 studies, the etripamil nasal spray dose of 70 mg was chosen for further evaluation in the phase 3 study.
Background
Self-administration of the investigational intranasal L-type calcium channel blocker , etripamil, during paroxysmal supraventricular tachycardia (PSVT) appeared safe and well tolerated in the phase 3 NODE-301 study (multicenter, randomized, double-blind, placebo-controlled , efficacy, and safety study of etripamil nasal spray for termination of spontaneous episodes of paroxysmal supraventricular tachycardia) in adults with sustained atrioventricular node-dependent PSVT. The NODE‐302 open‐label extension further characterized the safety and efficacy of etripamil.
Methods and results
Eligible patients were monitored using a self-applied cardiac monitoring system for 5 hours after self-administration of etripamil. The primary endpoint was time to conversion from PSVT with positive adjudication to sinus rhythm after etripamil treatment. The probability of conversion to sinus rhythm was reported using a Kaplan‐Meier plot.
Adverse events were based on self-reported symptoms and clinical assessments. Among 169 patients enrolled, 105 self-administered etripamil ≥1 time for perceived PSVT (median [range], 232 [8–584] days of follow-up).
The probability of conversion within 30 minutes of etripamil was 60.2% (mean conversion time, 15.5 minutes) among 188 PSVT episodes (92 patients) positively adjudicated as atrioventricular node dependent by independent ECG analysis .
Among 40 patients who self-treated 2 episodes, 75% had a significantly consistent response at 30 minutes; 9 did not convert in either episode and 21 converted in both episodes (χ2 =8.09; P = 0.0045).
Forty-five of 105 patients (42.9%) had ≥1 treatment-emergent adverse event, usually transient and mild to moderate, including nasal congestion (14.3%), nasal discomfort (14.3%), or rhinorrhea ( 12.4%).
No serious cardiac safety events were observed within 24 hours of etripamil administration.
Conclusions
In this extension study, investigational etripamil nasal spray was well tolerated for self-treatment of recurrent episodes of PSVT without medical supervision.
Comments
A fast-acting medication administered as a nasal spray could one day allow patients with intermittent rapid heartbeats to treat themselves as soon as they develop symptoms, according to new research published today in the Journal of the American Heart. Association , an open access, peer-reviewed journal of the American Heart Association . This new drug is still awaiting approval from the US Food and Drug Administration.
"This is a potentially new and exciting option for patients to safely self-treat their rapid heartbeats without direct medical supervision to avoid emergency room visits and medical interventions," said James E. Ip, MD, lead author. of the study and associate professor of clinical medicine at Weill Cornell Medicine at New York-Presbyterian Hospital in New York City.
About 1 in 300 people in the United States experience intermittent periods of rapid heartbeats (more than 100 beats per minute and, more typically, 150 to 200 beats per minute) in the lower chambers of the heart, a condition called paroxysmal supraventricular tachycardia .
The standard treatment during an episode is to slow the heart rate by performing physical actions called vagal maneuvers, one of which is done by trying to push, which is accomplished by exhaling with the stomach muscles but without letting the air out through the nose. or mouth. These types of actions can cause the vagus nerve to slow electrical conduction through the atrioventricular (AV) node, which regulates the timing of electrical pulses to the bottom of the heart. If self-administered vagal maneuvers are not effective (which occurs 20% to 40% of the time), the person should seek immediate treatment with intravenous medication in an emergency room to return the heart rate to normal. In the United States, about 50,000 emergency room visits a year are for paroxysmal supraventricular tachycardia.
In a previous study, people with the disorder were treated with etripamil or a placebo nasal spray for a single episode of tachycardia. Participants applied an electrocardiogram (ECG) patch at symptom onset, performed a vagal maneuver, and self-administered the nasal spray if rapid heartbeats continued, keeping the ECG patch on for at least five hours. In that study, the first time etripamil was used without direct supervision , normal heart rhythms were restored within 30 minutes in 54% of patients, compared with 35% with placebo, and the drug was found to be safe and well tolerated. The ECG patch is a wearable heart monitor that has a small device with an adhesive that adheres to the skin surface of the chest and connects wirelessly to a cell phone to transmit ECG data.
All people in that randomized trial were invited to participate in the current open-label study that allowed patients to self-treat with etripamil during multiple episodes of paroxysmal supraventricular tachycardia (PSVT). Of the 169 patients enrolled, 105 self-administered at least one dose of etripamil (70 mg) during the median study period of 232 days.
The new study found:
- Etripamil restored heart rate to normal within 30 minutes in 60.2% of 188 verified PSVT episodes, and within one hour in 75.1% of episodes.
- Of the 40 participants who self-treated two episodes, 63.2% responded to medication within 30 minutes. Nine people (23%) did not convert to a normal heart rate in either episode, and 21 (53%) converted to a normal heart rate in both episodes.
- Safety was assessed regardless of whether the episode was confirmed by ECG. Thirty-four participants (32.4%) reported one or more side effects of the medication, most commonly mild to moderate nasal congestion or discomfort, or a runny nose. There were no serious heart-related adverse events.
"There are no great options for patients to self-treat paroxysmal supraventricular tachycardia, and this condition can cause significant distress and anxiety." "Like an albuterol inhaler for patients with asthma or an epinephrine pen for patients who have severe allergies or anaphylaxis, etripamil nasal spray may be an excellent option for people who have paroxysmal supraventricular tachycardia."
Study details and background:
- The study began in December 2018 and ended in October 2020.
- Participants had an average age of 58 years, 62% were women, and about 83% were white adults, 8% were African American adults, 3% were Asian adults, 2% were Native Hawaiian or Pacific Islander adults, and 5% from other races.
- All participants had been diagnosed with paroxysmal supraventricular tachycardia and had experienced, on average, 9.7 episodes in the previous year. Most were taking long-acting medications to prevent rapid heartbeats. People were excluded from the study if they had other heart conditions, such as atrial fibrillation.
- The participants were good at detecting when they had fast heart rhythms, and 92 (87.6%) of them had one or more episodes confirmed by ECG. Verified episodes were used to evaluate the effectiveness of the medication.
- For people with atrial fibrillation (rapid, irregular heartbeats of the upper chambers of the heart), the use of etripamil to quickly reduce heart rate is being investigated.
Unlike previous studies that compared etripamil to a placebo, this open-label follow-up study was limited by not having a control group (no one took a placebo). The study is also limited by only including adults. Treatment with etripamil in children 6 to 17 years of age with paroxysmal supraventricular tachycardia is being evaluated in a separate study that will begin this year. Although the majority of participants in the current study identified as white, the researchers hope that the results are generalizable to people from other racial/ethnic groups because previous studies have shown that the metabolism of etripamil and its impact on the AV node are similar. regardless of race. /ethnicity.
Clinical perspective
What’s new?
Self-administration of the investigational intranasal L-type calcium channel blocker, etripamil, during paroxysmal supraventricular tachycardia (PSVT) appeared effective in NODE-302 (Multicenter, Open-Label, Safety Study of Etripamil Nasal Spray in Spontaneous Episodes of Tachycardia paroxysmal supraventricular) open-label extension study.
Etripamil was well tolerated and most adverse events were mild to moderate, local, and transient; no patient experienced any serious adverse events related to study drug for up to 11 repeat doses.
Similar to the NODE‐301 study, etripamil was associated with 60% conversion from PSVT to sinus rhythm within 30 minutes (75% within 60 minutes), with a median of 15.5 minutes to conversion.
What are the clinical implications?
Etripamil may be a potential therapeutic option for patients to self-treat recurrent episodes of PSVT without medical supervision.
This intranasal medication with rapid onset of action could be an alternative to pocket pill strategies for PSVT.
The use of etripamil could potentially reduce the use of emergency medical services to treat episodes of SPVT resistant to vagal maneuvers.
Final message Results from the NODE‐302 study suggest that investigational etripamil is a safe and effective self‐administered treatment for treating spontaneous PSVT refractory to vagal maneuvers (VM) without medical supervision. There were no signs of new safety problems or adverse events during this long-term follow-up of repeated administration of the drug for up to 11 episodes. This therapeutic approach could potentially reduce the use of emergency medical services to treat episodes of SPVT resistant to vagal maneuvers (VMs). Pending studies of a second dose of intranasal etripamil during ongoing PSVT without medical supervision will provide additional safety and efficacy data to evaluate its potential therapeutic application. |
The study was funded by Milestone Pharmaceuticals, the manufacturer of etripamil.
