Bruce S Stambler1, Paul Dorian2, Philip T Sager3, Douglas Wight4, Philippe Douville4, Diane Potvin5, Pirouz Shamszad6, Ronald J Haberman7, Richard S Kuk8, Dhanunjaya R Lakkireddy9, Jose M Teixeira10, Kenneth C Bilchick11, Roger S Damle12, Robert C Bernstein13, Wilson W Lam14, Gearoid O'Neill15, Peter A Noseworthy16, Kalpathi L Venkatachalam17, Benoit Coutu18, Blandine Mondésert19, Francis Plat20. 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: fplat@milestonepharma.com.
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).
RCT Entities:
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).