Wednesday, 17 April, 2024
HomeCardiology‘Home use’ tachycardia nasal spray shortens episodes – randomised US trial

‘Home use’ tachycardia nasal spray shortens episodes – randomised US trial

No medications are currently approved for acute termination of paroxysmal supraventricular tachycardia without medical supervision, but results of a recent trial show that a self-administered, ‘at home’ nasal spray, can dramatically reduce patients’ tachycardia episodes.

An analysis of the phase III randomised RAPID trial showed that the investigational L-type calcium channel blocker etripamil self-administered nasal spray shortened spontaneous paroxysmal supraventricular tachycardia episodes among patients in at-home settings to sinus rhythm within 30 minutes.

“Patients know they are having supraventricular tachycardia when these episodes occur,” said Dr Jayne Morgan of Piedmont Healthcare in Atlanta. “Generally, these episodes are very worrisome and will drive patients to seek medical care.”

Aside from symptoms, reports MedPage Today, supraventricular tachycardia can also increase risks of blood clotting and downstream strokes.

The probability of the primary endpoint of the study – conversion of adjudicated paroxysmal supraventricular tachycardia to sinus rhythm within 30 minutes – was 64.3% with etripamil, which had the option of repeat dosing, compared with 31.2% with placebo (HR 2.62, 95% CI 1.66-4.15, P<0.001), reported Dr James Ip of Weill Cornell Medical Centre in New York City, during the recent American Heart Association annual meeting (5-7 November).

At 90 minutes, 80.6% of the patients who self-administered etripamil converted to sinus rhythm compared with 60.7% of placebo patients (HR 1.93, 95% CI 1.35-2.75, P<0.001), which was maintained through the 5-hour observation period (82.7% vs 72%).

Median time to convert to sinus rhythm was 17.2 minutes with etripamil compared with 53.5 minutes with placebo, Ip noted.

In a prespecified pooled analysis, additional rescue medical interventions were less frequent with etripamil versus placebo (14.6% vs 25.4%, respectively, P=0.013).

“These results demonstrate a potential management strategy to self-treat episodes of paroxysmal supraventricular tachycardia with etripamil in a medically unsupervised setting,” Ip said.

RAPID’s results reverse the negative 2020 findings from the phase III NODE-301 trial, which tested self-administered etripamil in a similar patient population. That trial, which did not allow for repeat dosing, failed to show a significant benefit for the primary endpoint of conversion over five hours compared with placebo.

“This is an extraordinary, groundbreaking study showing the effectiveness of a new drug for home acute treatment,” said Dr Julia Indik, PhD, of the University of Arizona College of Medicine in Tuscon. “The number of patients to treat to avoid one emergency room treatment with etripamil is 13.”

She said what was missing from the study was a cost-effectiveness analysis, which will be needed if the drug is approved. It is also unclear how guideline writers will approach the concept of self-administration of this agent, she added.

The double-blind RAPID trial was conducted across 150 sites in the US, Europe and Canada; 255 patients with a history of documented sustained paroxysmal supraventricular tachycardia episodes that lasted at least 20 minutes were randomised to either etripamil (n=135) or placebo (n=120).

Mean patient age was about 54 years, 71% were women, and nearly all were white. Patients had experienced episodes of paroxysmal supraventricular tachycardia for about two years before entering the trial.

Treatment consisted of a 70-mg dose of etripamil followed by a second dose after 10 minutes if symptoms persisted, Ip explained. Patients who perceived they were having an episode applied an ECG monitor and performed a previously trained vagal manoeuvre.

The study was designed to determine results after 180 events were recorded.

As for safety, 50.4% of patients treated with etripamil experienced treatment-emergent adverse events that were mostly mild to moderate and transient, with the most frequent being nasal discomfort (23%), nasal congestion (12.6%), and rhinorrhea (8.9%). No serious cardiac adverse events were observed within 24 hours of etripamil self-administration.

Study details

Self-Administered Etripamil for Termination of Spontaneous Paroxysmal Supraventricular Tachycardia: Primary Analysis From the RAPID Study

Bruce Stambler, Alan Camm, Marco Alings, Amphia Ziekenhuis, Paul Dorian, Hein Heidbuchel, Jaco Houtgraaf, Jose Merino, Blandine Mondésert, Patrick Lyden, Atul Verma, John Wharton, Francis Plat, Silvia Shardonofsky, Michael Chen, James Ip.

Presented at American Heart Association annual meeting (5-7 November).

Introduction
Currently, no medications are approved for acute termination of paroxysmal supraventricular tachycardia (PSVT) without direct medical supervision. Etripamil is a fast-acting, intranasally administered, non-dihydropyridine, L-type calcium channel blocker in development for medically unsupervised self-administration to treat atrioventricular nodal-dependent PSVT.

Methods
RAPID (NCT03464019) is a randomised, double-blind, placebo-controlled Phase 3 study to evaluate the efficacy and safety of etripamil in patients experiencing a PSVT episode in an at-home setting. RAPID was conducted in ~150 sites in the United States, Europe, and Canada. After open-label etripamil test doses (2 x 70 mg, 10 min apart), patients ≥18 years with a history of-documented PSVT and sustained episodes(≥20 min), were randomised 1:1 (etripamil: placebo).
The treatment regimen was a first 70-mg dose, followed by a repeat 70-mg dose after 10 min if symptoms persisted. During a perceived PSVT episode, patients applied an ECG monitor (5-hr recording) and performed a previously trained vagal manoeuvre (VM); if the VM was unsuccessful, they self-administered the randomised treatment. The primary endpoint was time-to-termination of adjudicated PSVT and conversion to sinus rhythm (SR) for ≥30 sec within 30 min of treatment. Secondary endpoints included rates of patients seeking urgent care and rescue treatments received.

Results
Among 706 patients who received the test dose, 692 (98%) were randomised, 255 patients self-administered study drug regimen for a perceived PSVT event. All ECG tracings were independently, blindly adjudicated; 184 PSVT events were confirmed by adjudication as were the time of drug administration and of PSVT termination. The probability of conversion to SR within 30 min was 64.3% % with etripamil and 31.2% with placebo (hazard ratio 2.62; 95% CI 1.66-4.15; P<0.001). Additional rescue, medical interventions, from a prespecified pooled analysis, were less frequent with etripamil vs placebo (14.6% versus 25.4%, respectively P=0.013). Safety: 68 (50.4%) patients treated with etripamil had treatment-emergent AEs, mostly mild-to-moderate and transient, the most frequent being nasal discomfort (23%), nasal congestion (12.6%), and rhinorrhea (8.9%). No serious cardiac safety events were observed within 24 hrs of etripamil.

Conclusions
RAPID demonstrated clinical efficacy and favourable safety and tolerability, supporting potential outpatient use to effectively self-treat episodes of PSVT without medical supervision.

 

AHA presentation – Self-Administered Etripamil for Termination of Spontaneous Paroxysmal Supraventricular Tachycardia: Primary Analysis From the RAPID Study (Open access)

 

MedPage Today article – 'Groundbreaking' Results With Nasal Spray for Home Tachycardia Conversion (Open access)

 

See more from MedicalBrief archives:

 

A patient with palpitations: exceptions prove the rule

 

PoTS findings

 

How therapeutic fashion trumps medical evidence

 

 

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