Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia to Sinus Rhythm

  • J Am Coll Cardiol. 2018 Jul 31;72(5):489-497. doi: 10.1016/j.jacc.2018.04.082.
Bruce S Stambler  1 ,  Paul Dorian  2 ,  Philip T Sager  3 ,  Douglas Wight  4 ,  Philippe Douville  4 ,  Diane Potvin  5 ,  Pirouz Shamszad  6 ,  Ronald J Haberman  7 ,  Richard S Kuk  8 ,  Dhanunjaya R Lakkireddy  9 ,  Jose M Teixeira  10 ,  Kenneth C Bilchick  11 ,  Roger S Damle  12 ,  Robert C Bernstein  13 ,  Wilson W Lam  14 ,  Gearoid O'Neill  15 ,  Peter A Noseworthy  16 ,  Kalpathi L Venkatachalam  17 ,  Benoit Coutu  18 ,  Blandine Mondésert  19 ,  Francis Plat  20
Affiliations
  • 1. Piedmont Heart Institute, Atlanta, Georgia.
  • 2. University of Toronto & St. Michael's Hospital, Toronto, Ontario, Canada.
  • 3. Stanford University, Palo Alto, California.
  • 4. Milestone Pharmaceuticals, Montreal St.-Laurent, Quebec, Canada.
  • 5. Excelsus Statistics, Montreal, Quebec, Canada.
  • 6. Medpace, Cincinnati, Ohio.
  • 7. Top Line Pharma Contracting, Scottsdale, Arizona.
  • 8. Centra Stroobants Cardiovascular Center, Lynchburg, Virginia.
  • 9. University of Kansas Medical Center, Kansas City, Kansas.
  • 10. Black Hills Cardiovascular Research, Rapid City, South Dakota.
  • 11. University of Virginia Health System, Charlottesville, Virginia.
  • 12. South Denver Cardiology Associates, Littleton, Colorado.
  • 13. Sentara Norfolk General Hospital, Norfolk, Virginia.
  • 14. Baylor St. Luke's Medical Center, Houston, Texas.
  • 15. General Hospital, Sacramento, California.
  • 16. Mayo Clinic, Rochester, Minnesota.
  • 17. Mayo Clinic at Jacksonville, Jacksonville, Florida.
  • 18. Hotel-Dieu Recherche Cardiologie, Montreal, Quebec, Canada.
  • 19. Montreal Heart Institute, Montreal, Quebec, Canada.
  • 20. Milestone Pharmaceuticals, Montreal St.-Laurent, Quebec, Canada. Electronic address: [email protected].
PMID: 30049309 DOI: 10.1016/j.jacc.2018.04.082
Abstract

Background: There is no nonparenteral medication for the rapid termination of paroxysmal supraventricular tachycardia.

Objectives: The purpose of this study was to assess the efficacy and safety of etripamil nasal spray, a short-acting calcium-channel blocker, for the rapid termination of paroxysmal supraventricular tachycardia (SVT).

Methods: This phase 2 study was performed during electrophysiological testing in patients with previously documented SVT who were induced into SVT prior to undergoing a catheter ablation. Patients in sustained SVT for 5 min received either placebo or 1 of 4 doses of active compound. The primary endpoint was the SVT conversion rate within 15 min of study drug administration. Secondary endpoints included time to conversion and adverse events.

Results: One hundred four patients were dosed. Conversion rates from SVT to sinus rhythm were between 65% and 95% in the etripamil nasal spray groups and 35% in the placebo group; the differences were statistically significant (Pearson chi-square test) in the 3 highest active compound dose groups versus placebo. In patients who converted, the median time to conversion with etripamil was <3 min. Adverse events were mostly related to the intranasal route of administration or local irritation. Reductions in blood pressure occurred predominantly in the highest etripamil dose.

Conclusions: Etripamil nasal spray rapidly terminated induced SVT with a high conversion rate. The safety and efficacy results of this study provide guidance for etripamil dose selection for future studies involving self-administration of this new intranasal calcium-channel blocker in a real-world setting for the termination of SVT. (Efficacy and Safety of Intranasal MSP-2017 [Etripamil] for the Conversion of PSVT to Sinus Rhythm [NODE-1]; NCT02296190).

Keywords
atrioventricular nodal re-entrant tachycardia; atrioventricular reciprocating tachycardia; calcium-channel blocker; conversion rate; episodic treatment; paroxysmal supraventricular tachycardia.
Products