AzTrials
AzTrials

Paroxysmal Supraventricular TachycardiaPhase 3NODE-301NCT03464019

Efficacy and Safety of Etripamil for the Termination of Spontaneous Paroxysmal Supraventricular Tachycardia (PSVT).

A Phase 3 study testing Etripamil and Etripamil Test Dose in people with Paroxysmal Supraventricular Tachycardia, run by Milestone Pharmaceuticals Inc. at 161 sites in 9 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This was a three-part, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etripamil nasal spray (NS) self-administered by participants who experienced an episode of paroxysmal supraventricular tachycardia (PSVT) in an at-home setting. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Paroxysmal Supraventricular Tachycardia
What is being tested?
Etripamil and Etripamil Test Dose
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,097 participants
Where
161 sitesin 9 countries
Study dates
18 Jun 2018to 20 Jan 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants who met all of the following criteria were eligible to participate in the study:
  • Male or female participants at least 18 years of age;
  • Electrographically documented history of PSVT (e.g., electrocardiogram [ECG] obtained during an episode of PSVT, Holter monitoring, loop recorder, etc). If participant had a prior ablation for PSVT, participant had to have documented ECG evidence of PSVT post-ablation;
  • History of sustained episodes of PSVT (i.e., typically lasting approximately 20 minutes or longer);
  • Females of childbearing potential who were sexually active with a male partner who were not surgically sterile (i.e., vasectomy) had to agree to use a highly effective form of contraception from the time of signed informed consent until 30 days after the last administration of study drug. Females of childbearing potential had to have a negative serum pregnancy test result at the Screening Visit and at the Final Study Visit, a negative urine pregnancy test at the Test Dose Randomization Visit and had to use a highly effective form of contraception between the visits.
  • The following categories defined females who were NOT considered to be of childbearing potential:
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  • Premenopausal females with 1 of the following:
  • Documented hysterectomy,
  • Documented bilateral salpingectomy or tubal ligation; or
  • Documented bilateral oophorectomy, or
  • Postmenopausal females, defined as having amenorrhea for at least 12 months without an alternative medical cause;
  • Male participants, except those who were surgically sterile, had to use an approved highly effective form of contraception during the 3 days after any study drug administration; and
  • Signed written informed consent.

Who cannot join

  • Participants who met any of the following criteria were excluded from participation in the study:
  • Systolic blood pressure <90 mmHg after a 5-minute rest in sitting position at the Screening Visit or before the Test Dose. In participants treated with a chronic prophylactic drug for PSVT (e.g., beta-blockers, verapamil, and diltiazem), the drug could be stopped for at least the equivalent of 5 half-lives, participants could be rescreened once, and chronic use of the drug could not be restarted after randomization;
  • History of severe symptoms of hypotension, especially syncope, during episodes of PSVT;
  • History of atrial arrhythmia that did not involve the AV node as part of the tachycardia circuit (e.g., atrial fibrillation, atrial flutter, intra-atrial tachycardia);
  • History of allergic reaction to verapamil;
  • Current therapy with digoxin or any Class I or III antiarrhythmic drug, except if these drugs were stopped at least the equivalent of 5 half-lives before the Test Dose Randomization Visit;
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  • Current chronic therapy with oral amiodarone, or had taken oral amiodarone within 30 days prior to the Test Dose Randomization Visit;
  • Evidence of ventricular pre-excitation (e.g., delta waves, short PR interval <100 msec, Wolff-Parkinson-White syndrome) on the ECG performed at the Screening Visit or before the Test Dose administration;
  • Evidence of a second- or third-degree AV block on the ECG performed at the Screening Visit or before the Test Dose administration;
  • History or evidence of severe ventricular arrhythmia (e.g., torsades de pointes, ventricular fibrillation, or ventricular tachycardia);
  • Current congestive heart failure defined by the New York Heart Association Class II to IV;
  • History of Acute Coronary Syndrome or stroke within 6 months of screening;
  • Evidence of hepatic dysfunction defined as alanine aminotransferase or aspartate aminotransferase >3 × the upper limit of normal (ULN) or total bilirubin >2 × ULN at the Screening Visit, unless due to Gilbert syndrome;
  • Evidence of End-Stage Renal Disease as determined by an estimated glomerular filtration rate assessed at the Screening Visit of <15 mL/min/1.73m2, or requiring hemodialysis;
  • Females who were pregnant or lactating;
  • Evidence or history of any significant physical or psychiatric condition including drug abuse, which, in the opinion of the Investigator, could jeopardize the safety of participants, or affect their participation in the study. Additionally, the Investigator had the ability to exclude a participant if for any reason the Investigator judged the participant was not a good candidate for the study or would not be able to follow study procedures;
  • Participation in any investigational drug or device study or the use of any investigational drug or device within 30 days of the Screening Visit; or
  • Previously enrolled in a clinical trial for etripamil and received study drug during a perceived episode of PSVT.
  • Before randomization in the study, all participants received a Test Dose of an etripamil NS dosing regimen (etripamil 70 NS mg in Part 1 and in Parts 2 and 3 an initial dose of etripamil NS 70 mg followed by a second dose of etripamil NS 70 mg not earlier than 10 minutes and not later than 15 minutes after the first dose) to evaluate tolerability and to train participants on the study procedures. Participants who passed the Test Dose were randomized in the NODE-301 (2:1) or RAPID and RAPID Extension (2:1) study. A failure of the Test Dose was considered if participants met any of the following criteria occurring after administration of the either the first or second dose of etripamil NS 70 mg:
  • Any symptoms consistent with clinically severe hypotension such as pre-syncope, medically significant lightheadedness, syncope, nausea, or vomiting;
  • For participants with a pre-Test Dose Systolic Blood Pressure above 100 mmHg:
  • Decrease in SBP ≥40 mmHg after Test Dose; or
  • Post-Test Dose SBP <80 mmHg;
  • For participants with a pre-Test Dose SBP between 90 mmHg and 100 mmHg (inclusive):
  • Post-Test Dose SBP <75 mmHg;
  • Third-degree AV block, Mobitz II second-degree AV block, or Wenckebach with bradycardia ≤40 bpm;
  • New, significant sinus bradycardia Heart Rate ≤40 bpm or sinus pauses (≤3 seconds), if considered by the Investigator to put the participant's safety at risk if either were to occur while not under medical supervision;
  • Any new ventricular arrhythmia considered significant by the Investigator; or
  • Atrial fibrillation, atrial flutter or atrial tachycardia (event lasting longer than 30 seconds);
  • Refusal of second dose of etripamil Test Dose regimen.
  • Participants who failed the Test Dose proceeded in the study as follows:
  • If the Investigator identified a possible reversible cause of the initial Test Dose failure (e.g., concomitant medication such as beta-blocker), a re-challenge with a new Test Dose of etripamil dose regimen was possible after elimination of the reversible cause (e.g., withdrawal of concomitant therapy with the appropriate washout period). Participants could be randomized if they passed the second Test Dose and the cause of the Test Dose failure was eliminated for the duration of the study; or
  • If the Investigator could not identify a reversible cause of the initial Test Dose failure, or if the potential cause could not be modified (e.g., necessary antihypertensive drug to control blood pressure), participants could not be randomized and completed a Final Study Visit. Participants who failed the Test Dose are part of the Test Dose Only Population.

Trial locations and contacts

161 sites in 9 countries.

161 sites in 9 countries

United States54 sites

  • North Texas Research Associates

    Allen, Texas, 75013

  • MedStar Health Research Institute - Chesapeake Cardiovascular Associates

    Baltimore, Maryland, 21237

  • FWD Clinical Research

    Boca Raton, Florida, 33486

  • St. Luke's Idaho Cardiology Associates

    Boise, Idaho, 83702

  • Cary Research Group, LLC

    Cary, North Carolina, 27518

  • Medvin Clinical Research

    Cerritos, California, 91722

  • Medical University of South Carolina (MUSC)

    Charleston, South Carolina, 29425

  • Sanger Heart and Vascular Institute

    Charlotte, North Carolina, 28204

  • The Presbyterian Hospital DBA Novant Health Heart and Vascular Institute

    Charlotte, North Carolina, 28204

  • Hatton Institute for Research & Education, Trihealth, Inc. - Cardiology

    Cincinnati, Ohio, 45242

  • Prisma Health Midlands

    Columbia, South Carolina, 29203

  • IACT Health

    Columbus, Georgia, 31904

  • The Ohio State University (OSU) Wexner Medical Center

    Columbus, Ohio, 43210

  • Cardiovascular Clinic of North Texas

    Denton, Texas, 76201

  • Revival Research Institute, LLC

    Denton, Texas, 76201

  • AMITA Health Medical Group Heart & Vascular Elk Grpve Village

    Elk Grove Village, Illinois, 60007

  • Cardiovascular Associates of the Delaware Valley - Elmer

    Elmer, New Jersey, 08318

  • North Coast Cardiolog

    Encinitas, California, 92024

  • Titan Medical Research - Oceanside

    Encinitas, California, 92024

  • Piedmont Heart Institute- Fayetteville

    Fayetteville, Georgia, 30214

  • Piedmont Heart Institute-Fayetteville

    Fayetteville, Georgia, 30309

  • Parkview Physicians Group - Cardiology

    Fort Wayne, Indiana, 46845

  • Apex Trials Group

    Fort Worth, Texas, 76104

  • Cardiovascular Associates of the Delaware Valley

    Haddon Heights, New Jersey, 08035

  • Angiocardiac Care of Texas

    Houston, Texas, 77025

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Idaho Catalyst Clinical Research

    Idaho Falls, Idaho, 83404

  • Baptist Health Ambulatory Services d/b/a

    Jacksonville, Florida, 32207

  • Sparrow Clinical Research Institute

    Lansing, Michigan, 48912

  • Arkansas Cardiology

    Little Rock, Arkansas, 72205

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • South Denver Cardiology Associates, P.C

    Littleton, Colorado, 80120

  • Los Alamitos Cardiovascular

    Los Alamitos, California, 90720

  • Georgia Arrythmia Consultants&Research Institute

    Macon, Georgia, 31201

  • Rama Research LLC

    Marion, Ohio, 43302

  • United Health Research, LLC

    Miami, Florida, 33144

  • Atlantic Health System - Morristown Medical Center

    Morristown, New Jersey, 07962

  • Intermountain Medical Center

    Murray, Utah, 84157-7000

  • Columbia University

    New York, New York, 10032

  • New York Presbyterian Hospital/Weill Cornell Medical Center

    New York, New York, 10065

  • Amicis Research Center - Northridge

    Northridge, California, 91324

  • Cardiology Associates of Fairfield County

    Norwalk, Connecticut, 06905

  • RESPIRE Research

    Palm Springs, California, 92262

  • Arizona Arrhythmia Research Center

    Phoenix, Arizona, 85016

  • Monument Health Clinical Research, a department of Monument Health Rapid City Hospital, Inc

    Rapid City, South Dakota, 57701

  • Revival Research Institute, LLC - Southgate, MI

    Southgate, Michigan, 48195

  • Heart House Research Foundation, LLC

    Springfield, Ohio, 45505

  • Mercy Research

    St Louis, Missouri, 65804

  • Scott & White Memorial Hospital: Baylor Scott & White Research Institute

    Temple, Texas, 76508

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • ProMedica Toledo Hospital

    Toledo, Ohio, 43615

  • Bay Area Heart

    Webster, Texas, 77598

  • Mercy One Iowa Heart Center

    West Des Moines, Iowa, 50266

  • Clinical Trials of America, LLC - Monroe, LA

    West Monroe, Louisiana, 71291

Other trials in United States

Spain23 sites

  • Hospital General Universitario de Alicante

    Alicante, 03010

  • Hospital Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Hospital Universitari de Bellvitge

    Barcelona, 08907

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 8025

  • Hospital Universitario Reina Sofia

    Córdoba, Cordoba, 14004

  • Hospital Clinico Universitario Virgen de la Arrixaca

    El Palmar, Murcia, 30120

  • Martínez Hervás Cardiólogos

    Granada, Andalusia, 18002

  • Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves

    Granada, 18014

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28007

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario Puerta de Hierro

    Majadahonda, 28222

  • Hospital Universitario Virgen de la Victoria

    Málaga, Malaga, 29010

  • Hospital Universitario Central de Asturias

    Oviedo, 33011

  • Complejo Hospitalario de Navarra

    Pamplona, 31008

  • Hospital Universitari Sant Joan de Reus

    Reus, 43204

  • Hospital Universitario la Paz Rua Choupana

    Santiago de Compostela, 15706

  • Hospital Universitario Virgen Macarena

    Seville, 41009

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital General Universitario de Valencia (HGUV)

    Valencia, Valencia, 46014

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

  • Hospital Alvaro Cunqueiro

    Vigo, Pontevedra, 36213

  • Hospital Universitario Clínico Lozano Blesa

    Zaragoza, 50009

Other trials in Spain

Canada20 sites

  • Libin Cardiovascular Institute of Alberta - University of Calgary

    Calgary, Alberta, T2N 4Z6

  • Cambridge Cardiac Care Centre

    Cambridge, Ontario, N1R 6V6

  • Royal Alexandra Hospital

    Edmonton, Alberta, T5H 3V9

  • Dawson Road Medical Centre

    Guelph, Ontario, N1H 1B1

  • Dalhousie University - QEII Health Sciences Centre

    Halifax, Nova Scotia, B3H 3A7

  • Hamilton Health Sciences

    Hamilton, Ontario, L8L 0A6

  • London Health Sciences Centre

    London, Ontario, N6A 5A5

  • The Montreal Heart Institute

    Montreal, Quebec, H1T 1C8

  • CHUM Recherche Cardiologie

    Montreal, Quebec, H2X 0A9

  • McGill University Health Center - Research Institute

    Montreal, Quebec, H3G 1A4

  • Partners in Advanced Cardiac Evaluation (PACE) Cardiology Clinic

    Newmarket, Ontario, L3Y 2P6

  • Medical Arts Health Research Group - North Vancouver

    North Vancouver, British Columbia, V5Z 0A9

  • Institut Universitaire de Cardiologie et de Pneumologie De Quebec

    Québec, Quebec, G1V 4G5

  • CardioVasc HR

    Saint-Jean-sur-Richelieu, Quebec, J3A 1J2

  • CIUSSS de l'Estrie - CHUS

    Sherbrooke, Quebec, J1H 5N4

  • CSSS du Sud de Lanaudiere - Hopital Pierre Le Gardeur

    Terrebonne, Quebec, J6V 2H2

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • Vancouver Coastal Health Research

    Vancouver, British Columbia, V5Z 1M9

  • Victoria Cardiac Arrhythmia Trials, Inc.

    Victoria, British Columbia, V8T 1Z4

  • University of Manitoba, St Boniface General Hospital

    Winnipeg, Manitoba, R2H 2A6

Other trials in Canada

Netherlands17 sites

  • Meander Medisch Centrum - Locatie Amersfoort

    Amersfoort, 3813 TZ

  • Ziekenhuis Rijnstate - Locatie Arnhem

    Arnhem, 6815 AD

  • Rode Kruis Ziekenhuis

    Beverwijk, 1942 LE

  • Tergooiziekenhuizen Blaricum

    Blaricum, 1261 AN

  • Amphia Ziekenhuis - Locatie Breda Molengracht

    Breda, 4818 CK

  • IJsselland ziekenhuis

    Capelle aan den IJssel, 2906 ZC

  • Reinier de Graaf Gasthuis

    Delft, 2625 AD

  • Deventer Ziekenhuis

    Deventer, 7416 SE

  • Slingeland Ziekenhuis

    Doetinchem, 7009 BL

  • Ziekenhuis Gelderse Vallei

    Ede, 6716 RP

  • Ropcke-Zweers Ziekenhuis

    Hardenberg, 7772 SE

  • Treant Zorggroep

    Hoogeveen, 7909

  • Alrijne Ziekenhuis

    Leiderdorp, 2353 GA

  • Maastricht University Medical Center

    Maastricht, 6229 HX

  • Franciscus Gasthuis & Vlietland - Locatie Vlietland

    Schiedam, 3118 JH

  • Diakonessenhuis - Locatie Utrecht

    Utrecht, 3582 KE

  • Jeroen Bosch Ziekenhuis

    Utrecht, 3584 CX

Other trials in Netherlands

Poland15 sites

  • MICS Centrum Medyczne Torun

    Bydgoszcz, 85-065

  • Centrum Medyczne Kermed

    Bydgoszcz, 85-231

  • Specjalistyczna Praktyka Lekarska

    Katowice, 40-530

  • American Heart of Poland S.A., IV Oddzial Kardiologii Inwazyjnej, Elektrostymulacji i Angiologii

    Kędzierzyn-Koźle, Kedzierzyn Kozle, 43-450

  • Gabinety Daszmed

    Krakow, Krakov, 31-534

  • Prywatny Specjalistyczny Gabinet Internistyczny

    Libiąż, 32-590

  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny, Uniwersytetu Medycznego w Lodzi

    Lodz, Łódź Voivodeship, 92-213

  • Instytut Centrum Zdrowia Matki Polki

    Lodz, Łódź Voivodeship, 93-338

  • MEDICOME Sp. z o.o.

    Oświęcim, 32-600

  • SP ZOZ Szpital Specjalistyczny w Pulawach

    Puławy, 24-100

  • Kliniczny Szpital Wojewódzki nr 2, Rzeszów

    Rzeszów, Rzeszow, 35-301

  • NZOZ Pro Cordis Sopockie Centrum Badan Kardiologicznych

    Sopot, 81-717

  • Osrodek Badan Klinicznych CLINSANTE S.C.

    Torun, 87-100

  • X Oddzial Kardiologii Inwazyjnej, Elektrofizjologii i Elektrostymulacji

    Tychy, 43-100

  • Kardiosystem

    Warsaw, 04-628

Other trials in Poland

Belgium11 sites

  • Clinique Du Sud- Luxembourg

    Arlon, 6700

  • Imelda Hospital

    Bonheiden, 2820

  • UVC Brugmann University Hospital - Centre Hospitalier Universitaire (CHU)

    Brussels, 1020

  • Universite Libre de Bruxelles (ULB) - Hopital Erasme

    Brussels, 1070

  • Antwerp University Hospital (UZA)

    Edegem, 2650

  • Grand Hopital de Charleroi (GHdC) - Site Saint-Joseph

    Gilly, 6060

  • Pharmacy Campus Virga Jesse (losplaats 7)

    Hasselt, 3500

  • University Hospital (UZ) Leuven

    Leuven, 3000

  • Regional Hospital Centre Citadelle

    Liège, 3000

  • CHU Ambroise Pare

    Mons, 7000

  • CHU UCL Namur - Site Godinne

    Yvoir, 5530

Other trials in Belgium

France7 sites

  • CHRU Besancon - Hopital Jean Minjoz

    Besançon, Besancon, 25030

  • CHRU de Brest - Hopital de la Cavale Blanche

    Brest, 29609

  • HCL Hopital Louis Pradel

    Bron, 69677

  • Hopital Saint-Louis de La Rochelle

    La Rochelle, 17000

  • CHU Grenoble-Alpes - Hopital Michallon

    La Tronche, Grenoble, 38043

  • CHU de Lille - Institut Cœur Poumon

    Lille, 59037

  • Centre Hospitalier de Pau

    Pau, 64000

Other trials in France

Germany7 sites

  • Vivantes Klinikum Neukoelln

    Berlin, 12351

  • FAZ Dresden-Neustadt GbR

    Dresden, 01099

  • Kardiologische Praxis

    Dresden, 04779

  • Maerkische Gesundheitsholding GmbH - Klinikum Luedenscheid

    Lüdenscheid, Ludenscheid, 58515

  • Peter Osypka Herzzentrum Munchen

    München, Munchen, 81379

  • Kardiologische Gemeinschaftspraxis Papenburg

    Papenburg, 26871

  • Zentrum fuer Praevention und Rehabilitation

    Siegen, 57072

Other trials in Germany

Hungary7 sites

  • Dr Lakatos Ferenc Belgyogyaszati-Kardiologiai Maganrendelo

    Békéscsaba, Bekescaba, 5600

  • Del-pesti Centrumkorhaz

    Budapest, 1097

  • Magyar Honvedseg Egeszsegugyi Kozpont

    Budapest, 1134

  • Nehezlegzes Ambulancia

    Debrecen, Debrecon, 4026

  • Debreceni Egyetem Klinikai

    Debrecen, 4032

  • CRU Hungary Kft.

    Encs, H-3860

  • Belvarosi Egeszseghaz

    Zalaegerszeg, 8900

Other trials in Hungary

About this study

Official title: Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Efficacy, and Safety Study of Etripamil Nasal Spray for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia. NODE 301 and RAPID Studies

This was a three-part, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etripamil nasal spray (NS) self-administered by participants who experienced an episode of paroxysmal supraventricular tachycardia (PSVT) in an at-home setting.

NODE-301 Part 1 included participants that received the randomized study drug to treat an episode of PSVT until the 150th positively adjudicated PSVT episode. Part 2 (also referred as the RAPID study) included participants that did not receive the randomized study drug in Part 1 and newly enrolled participants until the 180th positively adjudicated PSVT episode in Part 2. The study continued for approximately 6 months after the 180th positively adjudicated PSVT episode in Part 2 and this extension is referred to as Part 3 (also referred to as RAPID Extension).

Read the detailed description

NODE-301 was a three-part, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etripamil NS self-administered by participants who experienced an episode of PSVT in an at-home setting. Each episode was documented by an ambulatory Cardiac Monitoring System (CMS) that was placed on the chest by the participants or caregiver when symptoms begin and recorded at least 5 hours of continuous electrocardiogram (ECG).

This was an event-driven study. The study comprised of three parts: Parts 1, 2, and 3.

NODE-301 Part 1 included participants that received the randomized study drug to treat an episode of PSVT until the 150th positively adjudicated PSVT episode (January 15th, 2020). Participants were randomized to etripamil 70 mg or placebo in a 2:1 ratio. Participants had a Test Dose Randomization Visit where they received 70 mg etripamil in sinus rhythm and a Treatment Period during which they could administer the randomized study drug during a perceived episode of PSVT.

Part 2 (also referred as the RAPID study) included participants that did not use the randomized study drug to treat a perceived episode of PSVT before the Part 1 data cutoff and newly enrolled participants. Before randomization in the RAPID study, all participants received a Test Dose of etripamil consisting of an initial dose of etripamil 70 mg followed by a second dose of etripamil 70 mg 10 minutes later to evaluate tolerability and to train participants on the study procedures. After a successful Test Dose, participants in Part 2 were randomized to etripamil or placebo in a 1:1 ratio. When experiencing a PSVT episode, participants were instructed to administer a first dose of randomized study drug (70 mg etripamil or placebo) followed 10 minutes later, if PSVT symptoms persisted, by a second dose of study drug (70 mg etripamil or placebo). After having administered the randomized study drug for a perceived episode of PSVT, participants could enter an open-label period during which they had the possibility to treat a second episode of PSVT with open-label etripamil (70 mg etripamil with optional second dose of 70 mg etripamil).

Part 2 continued until the 180th positively adjudicated PSVT episode (the data on which the primary efficacy analysis of RAPID was conducted) (July 20th 2022). The study continued for approximately 6 months after the 180th positively adjudicated PSVT episode in Part 2 and this extension is referred to as Part 3 (also referred to as RAPID Extension). The design of Parts 2 and 3 were the same and therefore their results are combined in this publication.

NODE-301 study comprised 6 arms:

  • 2 arms consisting of participants enrolled in Part 1 that treated a perceived episode of PSVT with randomized study drug (etripamil NS 70 mg or placebo) in a 2:1 ratio.
  • 1 arm consisting of participants that only received the Test Dose in Part 1.
  • 2 arms consisting of participants enrolled in Parts 2 and 3 that treated a perceived episode of PSVT with randomized study drug (etripamil NS 70 mg with optional second dose of 70 mg etripamil or placebo) in a 1:1 ratio and could be enrolled in the open-label period to treat an additional PSVT episode with etripamil
  • 1 arm consisting of participants that only received the Test Dose in Parts 2 and 3.
Being tested
Etripamil, Placebo, Etripamil Test Dose
Keywords
Paroxysmal supraventricular tachycardia, cardiac monitoring, atrioventricular nodal reentrant tachycardia, atrioventricular reciprocating tachycardia, calcium channel blocker administered at home, conversion rate
Medical subject headings
Tachycardia, Ventricular, Tachycardia, Atrioventricular Nodal Reentry

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EtripamilDrug

    Also called MSP-2017

    Etripamil administered via the Aptar Pharma Nasal Spray Bidose System, supplied as prefilled devices packaged into child-resistant boxes with instructions for use provided in the study drug box.

  • PlaceboDrug

    Placebo administered via the Aptar Pharma Nasal Spray Bidose System, supplied as prefilled devices packaged into child-resistant boxes with instructions for use provided in the study drug box.

  • Etripamil Test DoseDrug

    Also called MSP-2017 Test Dose

    During the Test Dose, etripamil administered via the Aptar Pharma Nasal Spray Bidose System, supplied as prefilled devices packaged into child-resistant boxes with instructions for use provided in the study drug box.

Study groups in NCT03464019
Study groupRoleWhat they receive
Part 1: Etripamil 70 mg Single DoseExperimentalSelf-administration of a single dose etripamil 70 mg for a perceived episode of PSVT.
Receives: Drug: Etripamil
Part 1: Placebo Single DosePlacebo comparatorSelf-administration of a single dose of placebo for a perceived episode of PSVT.
Receives: Drug: Placebo
Part 1: Test dose only (etripamil 70 mg)OtherSingle test dose of etripamil 70 mg in sinus rhythm
Receives: Drug: Etripamil Test Dose
Part 2 & Part 3: Etripamil 70 mg with Optional Second DoseExperimentalSelf-administration of 70 mg etripamil for a perceived episode of PSVT followed 10 minutes later by an optional second dose of 70 mg etripamil, if symptoms persisted. Participants could be enrolled in the open-label period to treat an additional PSVT episode with etripamil.
Receives: Drug: Etripamil
Part 2 & Part 3: Placebo with Optional Second DosePlacebo comparatorSelf-administration of placebo for a perceived episode of PSVT followed 10 minutes later by an optional second dose of placebo, if symptoms persisted. Participants could be enrolled in the open-label period to treat an additional PSVT episode with etripamil.
Receives: Drug: Placebo
Part 2 & Part 3: Test dose only (etripamil 70 mg + 70 mg)OtherRepeat Test Dose of etripamil 70 mg (2X 70mg) 10 minutes apart in sinus rhythm
Receives: Drug: Etripamil Test Dose

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration.

    The primary efficacy endpoint is defined as an adjudicated termination of a positively adjudicated episode of PSVT (AV nodal reentrant tachycardia or AV reentrant tachycardia determination if possible) and conversion to sinus rhythm (SR) for at least 30 seconds within 5 hours (NODE-301 Part 1), or 30 minutes (NODE-301 Parts 2 and 3) of start of study drug dosing.

    Measured: NODE-301 Part 1: Within 5 hours of start of study drug dosing. NODE-301 Parts 2 and 3: Within 30 minutes of start of study drug dosing.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2018
  2. Study start18 Jun 2018
  3. Primary completion20 Jan 2023
  4. Study completion20 Jan 2023

Why it stopped: The closure of the event-driven study was terminated due to the total sample size was reached.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
NODE-301 study comprised 6 arms: * 2 arms consisting of participants enrolled in Part 1 that treated a perceived episode of PSVT with randomized study drug (etripamil NS 70 mg or placebo) in a 2:1 ratio. * 1 arm consisting of participants that only received the Test Dose in Part 1. * 2 arms consisting of participants enrolled in Parts 2 and 3 that treated a perceived episode of PSVT with randomized study drug (etripamil NS 70 mg with optional second dose of 70 mg etripamil or placebo) in a 1:1 ratio and could be enrolled in the open-label period to treat an additional PSVT episode with etripamil * 1 arm consisting of participants that only received the Test Dose in Parts 2 and 3.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,097 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03464019
Sponsor's protocol ID
MSP-2017-1138
Other IDs
2018-000308-41, 2018
Acronym
NODE-301
Status last verified
May 2024
First submitted
7 Mar 2018
Last updated
12 Jul 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Stambler BS, Camm AJ, Alings M, Dorian P, Heidbuchel H, Houtgraaf J, Kowey PR, Merino JL, Mondesert B, Piccini JP, Pokorney SD, Sager PT, Verma A, Wharton JM, Bharucha DB, Plat F, Shardonofsky S, Chen M, Ip JE; RAPID Investigators. Self-administered intranasal etripamil using a symptom-prompted, repeat-dose regimen for atrioventricular-nodal-dependent supraventricular tachycardia (RAPID): a multicentre, randomised trial. Lancet. 2023 Jul 8;402(10396):118-128. doi: 10.1016/S0140-6736(23)00776-6. Epub 2023 Jun 15.

    PubMed 37331368

  • Stambler BS, Plat F, Sager PT, Shardonofsky S, Wight D, Potvin D, Pandey AS, Ip JE, Coutu B, Mondesert B, Sterns LD, Bennett M, Anderson JL, Damle R, Haberman R, Camm AJ. First Randomized, Multicenter, Placebo-Controlled Study of Self-Administered Intranasal Etripamil for Acute Conversion of Spontaneous Paroxysmal Supraventricular Tachycardia (NODE-301). Circ Arrhythm Electrophysiol. 2022 Dec;15(12):e010915. doi: 10.1161/CIRCEP.122.010915. Epub 2022 Nov 28.

    PubMed 36441560

  • Stambler BS, Plat F, Sager PT, Lubkov V, Shardonofsky S, Wight D, Chen M, Camm AJ. Rationale for and design of a multicenter, placebo-controlled, phase 3 study to assess efficacy and safety of intranasal etripamil for the conversion of paroxysmal supraventricular tachycardia. Am Heart J. 2022 Nov;253:20-29. doi: 10.1016/j.ahj.2022.06.005. Epub 2022 Jun 18.

    PubMed 35728658

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Etripamil and Etripamil Test Dose in people with Paroxysmal Supraventricular Tachycardia, run by Milestone Pharmaceuticals Inc. at 161 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 161 sites in United States, Spain, Canada, Netherlands, Poland and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. (time frame: NODE-301 Part 1: Within 5 hours of start of study drug dosing. NODE-301 Parts 2 and 3: Within 30 minutes of start of study drug dosing.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03464019, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2024.

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