Multicenter, Phase 2, Randomized Controlled Study of the Efficacy and Safety of Etripamil Nasal Spray for the Acute Reduction of Rapid Ventricular Rate in Patients With Symptomatic Atrial Fibrillation (ReVeRA-201)

Circ Arrhythm Electrophysiol. 2023 Dec;16(12):639-650. doi: 10.1161/CIRCEP.123.012567. Epub 2023 Nov 11.

Abstract

Background: Despite chronic therapies, atrial fibrillation (AF) leads to rapid ventricular rates (RVR) often requiring intravenous treatments. Etripamil is a fast-acting, calcium-channel blocker administered intranasally affecting the atrioventricular node within minutes.

Methods: Reduction of Ventricular Rate in Patients with Atrial Fibrillation evaluated the efficacy and safety of etripamil for the reduction of ventricular rate (VR) in patients presenting urgently with AF-RVR (VR ≥110 beats per minute [bpm]), was randomized, double-blind, placebo-controlled, and conducted in Canada and the Netherlands. Patients presenting urgently with AF-RVR were randomized (1:1, etripamil nasal spray 70 mg: placebo nasal spray). The primary objective was to demonstrate the effectiveness of etripamil in reducing VR in AF-RVR within 60 minutes of treatment. Secondary objectives assessed achievement of VR <100 bpm, reduction by ≥10% and ≥20%, relief of symptoms and treatment effectiveness; adverse events; and additional measures to 360 minutes.

Results: Sixty-nine patients were randomized, 56 dosed with etripamil (n=27) or placebo (n=29). The median age was 65 years; 39% were female patients; proportions of AF types were similar between groups. The difference of mean maximum reductions in VR over 60 minutes, etripamil versus placebo, adjusting for baseline VR, was -29.91 bpm (95% CI, -40.31 to -19.52; P<0.0001). VR reductions persisted up to 150 minutes. Significantly greater proportions of patients receiving etripamil achieved VR reductions <100 bpm (with longer median duration <100 bpm), or VR reduction by ≥10% or ≥20%, versus placebo. VR reduction ≥20% occurred in 66.7% of patients in the etripamil arm and no patients in placebo. Using the Treatment Satisfaction Questionnaire for Medication-9, there was significant improvement in satisfaction on symptom relief and treatment effectiveness with etripamil versus placebo. Serious adverse events were rare; 1 patient in the etripamil arm experienced transient severe bradycardia and syncope, assessed as due to hypervagotonia.

Conclusions: Intranasal etripamil 70 mg reduced VR and improved symptom relief and treatment satisfaction. These data support further development of self-administered etripamil for the treatment of AF-RVR.

Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04467905.

Keywords: ECG; atrial fibrillation; emergency department; etripamil; heart rate; nasal sprays.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / diagnosis
  • Atrial Fibrillation* / drug therapy
  • Benzoates / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Nasal Sprays
  • Treatment Outcome

Substances

  • Nasal Sprays
  • etripamil
  • Benzoates

Associated data

  • ClinicalTrials.gov/NCT04467905