{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:39:52Z","timestamp":1790631592084,"version":"4.1.0"},"reference-count":12,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Pharmacologic termination of paroxysmal supraventricular tachycardia (PSVT) often requires medically supervised intervention. Intranasal etripamil, is an investigational fast-acting, nondihydropyridine, L-type calcium channel blocker, designed for unsupervised self-administration to terminate atrioventricular nodal\u2013dependent PSVT. Phase 2 results showed potential safety and efficacy of etripamil in 104 patients with PSVT.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>NODE-301, a phase 3, multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of etripamil nasal spray administered, unsupervised in patients with symptomatic sustained PSVT. After a medically supervised etripamil test dose while in sinus rhythm, patients were randomized 2:1 to receive etripamil 70 mg or placebo. When PSVT symptoms developed, patients applied a cardiac monitor and attempted a vagal maneuver; if symptoms persisted, they self-administered blinded treatment. An independent Adjudication Committee reviewed continuous electrocardiogram recordings. The primary efficacy endpoint was termination of adjudicated PSVT within 5 hours after study drug administration.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              NODE-301 accrued 156 positively adjudicated PSVT events treated with etripamil (n=107) or placebo (n=49). The hazard ratio for the primary endpoint, time-to-conversion to sinus rhythm during the 5-hour observation period, was 1.086 (95% CI, 0.726\u20131.623;\n              <jats:italic>P<\/jats:italic>\n              =0.12). In predefined sensitivity analyses, etripamil effects (compared with placebo) occurred at 3, 5, 10, 20, and 30 minutes (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). For example, at 30 minutes, there was a 53.7% of SVT conversion in the treatment arm compared to 34.7% in the placebo arm (hazard ratio, 1.87 [95% CI, 1.09\u20133.22];\n              <jats:italic>P<\/jats:italic>\n              =0.02). Etripamil was well tolerated; adverse events were mainly related to transient nasal discomfort and congestion (19.6% and 8.0%, respectively, of randomized treatment-emergent adverse events.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Although the primary 5-hour efficacy endpoint was not met, analyses at earlier time points indicated an etripamil treatment effect in terminating PSVT. Etripamil self-administration during PSVT was safe and well tolerated. These results support continued clinical development of etripamil nasal spray for self-administration during PSVT in a medically unsupervised setting.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT03464019.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.122.010915","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T16:40:56Z","timestamp":1669653656000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["First Randomized, Multicenter, Placebo-Controlled Study of Self-Administered Intranasal Etripamil for Acute Conversion of Spontaneous Paroxysmal Supraventricular Tachycardia (NODE-301)"],"prefix":"10.1161","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct03464019","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5692-2619","authenticated-orcid":true,"given":"Bruce S.","family":"Stambler","sequence":"first","affiliation":[{"name":"Piedmont Heart Institute, Atlanta, GA (B.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4436-5218","authenticated-orcid":true,"given":"Francis","family":"Plat","sequence":"additional","affiliation":[{"name":"Milestone Pharmaceuticals, Montr\u00e9al, Qu\u00e9bec, Canada (F.P., S.S., D.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7055-1786","authenticated-orcid":true,"given":"Philip T.","family":"Sager","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute &amp; Department of Medicine, Stanford University, Palo Alto, CA (P.T.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Shardonofsky","sequence":"additional","affiliation":[{"name":"Milestone Pharmaceuticals, Montr\u00e9al, Qu\u00e9bec, Canada (F.P., S.S., D.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Wight","sequence":"additional","affiliation":[{"name":"Milestone Pharmaceuticals, Montr\u00e9al, Qu\u00e9bec, Canada (F.P., S.S., D.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Potvin","sequence":"additional","affiliation":[{"name":"Excelsus Statistics, Montr\u00e9al, Qu\u00e9bec\u201a Canada (D.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2307-2376","authenticated-orcid":true,"given":"A. Shekhar","family":"Pandey","sequence":"additional","affiliation":[{"name":"Cambridge Cardiac Care Centre, Cambridge, Ontario, Canada (A.S.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Ip","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical Center, New York-Presbyterian Hospital, New York, NY (J.E.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Coutu","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l\u2019 Universit\u00e9 de Montr\u00e9al Montr\u00e9al, Qu\u00e9bec, Canada (B.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7777-5689","authenticated-orcid":true,"given":"Blandine","family":"Mond\u00e9sert","sequence":"additional","affiliation":[{"name":"Montr\u00e9al Heart Institute, Universit\u00e9 de Montr\u00e9al, Qu\u00e9bec\u201a Canada (B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3096-2548","authenticated-orcid":true,"given":"Laurence D.","family":"Sterns","sequence":"additional","affiliation":[{"name":"Victoria Cardiac Arrhythmia Trials, Inc, Victoria, British Columbia\u201a Canada (L.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Bennett","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Innovation\u201a Division of Cardiology, University of British Columbia, Vancouver, Canada (M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0825-8685","authenticated-orcid":true,"given":"Jeffrey L.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Intermountain Medical Center, Murray, UT (J.L.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Damle","sequence":"additional","affiliation":[{"name":"South Denver Cardiology Associates, PC, Littleton, CO (R.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2087-2132","authenticated-orcid":true,"given":"Ronald","family":"Haberman","sequence":"additional","affiliation":[{"name":"Top Line Arrhythmia Contractors, LLC, Scottsdale, AZ (R.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2536-2871","authenticated-orcid":true,"given":"A. John","family":"Camm","sequence":"additional","affiliation":[{"name":"St. George\u2019s University of London, London, England (A.J.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz467"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/cir.0000000000000310"},{"key":"e_1_3_3_4_2","volume-title":"Clinical Arrhythmology and Electrophysiology: A Companion to Braunwald\u2019s Heart Disease","author":"Issa ZF","year":"2012","unstructured":"Issa, ZF, Miller, JM, Zipes, DP. Clinical Arrhythmology and Electrophysiology: A Companion to Braunwald\u2019s Heart Disease. 2nd ed. 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