Etripamil Nasal Spray in Paroxysmal SVT Speeds Conversion to Sinus Rhythm: RAPID

CHICAGO, IL—Full results of the RAPID trial testing etripamil nasal spray for patients with paroxysmal supraventricular tachycardia (PSVT) show the self-administered treatment is safe and effective, and that it might reduce the need for emergency room trips and medical interventions.

Presenting the data today at the American Heart Association 2022 Scientific Sessions, James Ip, MD (NewYork-Presbyterian/Weill Cornell Medicine, New York, NY), said the agent, designed to be used by patients as soon as they feel symptoms, satisfies an “unmet” need for an easy, convenient, fast-acting therapy that can be administered by patients without medical supervision.

Top-line results were released last month by trial sponsor Milestone Pharmaceuticals, as reported by TCTMD. Etripamil is an investigational, L-type channel calcium channel blocker formulated for intranasal spray. RAPID was conducted at more than 100 sites in nine countries.

Detailed Results

In a clarification to the information released earlier, RAPID investigators screened 706 patients but ultimately randomized 692, of which 102 discontinued before the trial’s main analysis began and 335 had no PSVT episode during the trial but are still being followed in the RAPID Extension study.

Thus, among 120 patients randomized to placebo and 135 to etripamil (all of whom were followed for safety), just 85 and 99, respectively, treated their episodes with the assigned nasal spray—etripamil or placebo. Importantly, unlike prior studies of etripamil in SVT, RAPID allowed patients to administer a second 70-mg dose (same as the first) if symptoms persisted beyond 10 minutes.

By 30 minutes, as previously reported, the probability of conversion to sinus rhythm was 64.3% in patients randomized to the study drug as compared with 31.2% of those randomized to placebo (HR 2.62; 95% CI 1.66-4.15). The median time to conversion was just 17 minutes, nearly three times lower than that seen in the placebo arm.

The difference in the proportion of patients in sinus rhythm showed signs of shrinking at 60 minutes (73.5% vs 54.5%) and 300 minutes (82.7% vs 72%), but remained statistically greater in the etripamil group.

Importantly, said Ip, the data to date, including results from the earlier NODE 301 study, show a clear pattern of fewer patients seeking medical intervention for their PSVT and fewer emergency departments visits. Pooling patients from RAPID and NODE 301, the number of patients seeking medical interventions was 15% in the etripamil group compared with 25% in the placebo-treated patients (P = 0.13). The numbers of patients who headed to the emergency room for help were 14% and 22%, respectively (P = 0.035).

Expanding Options

“There are an estimated 1.2 to 2 million patients with PSVT,” Ip told TCTMD in an email. “Having an option to self-treat PSVT that is safe and effective would certainly help patients and expands their treatment options from what is currently available, [namely] catheter ablation versus maintenance/daily therapy—which may have some side effects—or pill-in-the-pocket treatment, which has not been shown to be safe and effective and is associated with possible hypotension and syncope.”

For patients, having the option of self-administering a treatment that can swiftly terminate PSVT and prevent them from heading for medical assistance is a key benefit, Ip added.

Julia H. Indik, MD, PhD (University of Arizona College of Medicine, Tucson), discussing the results after Ip’s late-breaking presentation, agreed. “One thing that patients really care about is they really want to be able to convert quickly and they certainly don’t want to be dragging themselves to the emergency room,” she said. “The number needed to treat would be about 13 to prevent an ER visit.”

While effectiveness is well established, this trial, while larger than others before it, does not look at whether it will be cost-effective or affordable for patients, she noted. Patient satisfaction is also important: “By converting patients sooner, does that offset any discomfort from the nasal congestion, and also [will this] impact on the decision to ablate?”

Last but not least, Indik said, US guidelines dating back to 2015 made room for self-administration of beta-blockers, diltiazem, or verapamil for “infrequent and well-tolerated episodes of SVT,” a class IIb recommendation, although the more-recent European guidelines did not support that approach. Whether RAPID is enough to influence future guidelines remains to be seen, she added.

Ip, during the discussion that followed his presentation, observed that so far nasally administered etripamil looks safer than a pill-in-the-pocket approach, and as a result it’s being explored for other arrhythmias beyond SVT.

“Because of its mechanism of action on L-type calcium channel blockers, it can potentially be used for other settings besides PSVT,” Ip told TCTMD. “One example that is being evaluated is etripamil's potential use for acute heart rate control of atrial fibrillation with rapid ventricular rates,” something now being tested in the ReVeRA-201 trial.