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Paroxysmal Supraventricular TachycardiaPhase 3NCT04072835

Safety Study of Etripamil Nasal Spray for Patients With Paroxysmal Supraventricular Tachycardia. NODE-303

A Phase 3 study testing Etripamil NS in people with Paroxysmal Supraventricular Tachycardia, run by Milestone Pharmaceuticals Inc. at 124 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

NODE-303 was a multi-center, open label study to evaluate the safety of etripamil NS in participants with Paroxysmal Supraventricular Tachycardia (PSVT). Participants were provided with an ambulatory Cardiac Monitoring System (CMS) to help document PSVT episodes. 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 NS
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,116 participants
Where
124 sitesin 5 countries
Study dates
23 Sep 2019to 26 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

  • A participant was eligible for study participation if they met all of the following criteria:
  • Had been diagnosed with PSVT by a medical professional, and reported having at least one previous episode of PSVT. For clarity, PSVT referred to episodic Supraventricular Tachycardia (SVT) that included the atrioventricular (AV) node as a critical part of reentrant circuit.
  • Was at least 18 years of age;
  • Signed NODE-303 written informed consent
  • Women of childbearing potential had to be willing to use at least 1 form of contraception during the trial, and had to be willing to discontinue from the study should they have become or planned to become pregnant. Postmenopausal females were defined as having amenorrhea for at least 12 months prior to Screening without an alternative medical cause.
  • Willing and able to comply with study procedures

Who cannot join

  • A participant was excluded from the study if they met any of the following criteria:
  • Participants with only a history of atrial arrhythmia that did not involve the atrioventricular (AV) node as part of the tachycardia circuit (e.g. atrial fibrillation, atrial flutter, intra-atrial tachycardia) were not eligible. Participants with a history of these tachycardias who were also diagnosed with PSVT were eligible.
  • History of allergic reaction to verapamil
  • Current therapy with digoxin, or any Class I or III antiarrhythmic drug. Participants could be eligible if these drugs were stopped at least five half-lives before the administration of etripamil NS. The only exception was amiodarone which had to be stopped 30 days before enrollment.
  • History or evidence of ventricular pre-excitation, e.g., delta waves, Wolff- Parkinson-White syndrome
  • History or evidence of a second- or third-degree AV block
Show all 19Show fewer
  • History or evidence of severe ventricular arrhythmia (e.g., torsades de pointes, ventricular fibrillation, or sustained ventricular tachycardia).
  • Symptoms of congestive heart failure New York Heart Association Class II to IV
  • SBP < 90 mmHg at Screening, Baseline or any Follow-up Visit.
  • Severe symptoms of hypotension experienced during PSVT episodes.
  • Significant physical or psychiatric condition including alcoholism or drug abuse, which, in the opinion of the Investigator, could jeopardize the safety of the participant, or impede the participant's capacity to follow the study procedures
  • History of syncope due to an arrhythmic etiology at any time, or history in last 5 years of unexplained syncope
  • Was pregnant or breastfeeding
  • Previously enrolled in a clinical trial for etripamil and received study drug or participation in any clinical trial for other investigational products or medical devices within 30 days of Screening.
  • History of Acute Coronary Syndrome (ACS) or stroke within 6 months of screening
  • Evidence of renal dysfunction as determined by an estimated glomerular filtration rate assessed at the Screening Visit as follows:
  • <60mL/min/1.73m2 for participants <60 years of age;
  • <40mL/min/1.73m2 for participants ≥60 and <70 years of age
  • <35mL/min/1.73m2 for participants ≥70 years of age

Trial locations and contacts

124 sites in 5 countries.

124 sites in 5 countries

United States61 sites

  • 1047

    Austin, Texas, 78705

  • 1092

    Austin, Texas, 78705

  • 1078

    Boston, Massachusetts, 02215

  • 1042

    Bradenton, Florida, 34208

  • 1010

    Bridgeport, Connecticut, 06610

  • 1024

    Canton, Ohio, 44710

  • 129

    Charlotte, North Carolina, 28204

  • 1065

    Charlotte, North Carolina, 28277

  • 123

    Cincinnati, Ohio, 45242

  • 1115

    Coeur d'Alene, Idaho, 83814

  • 142

    Columbus, Ohio, 31904

  • 1123

    Corvallis, Oregon, 97330

  • 1022

    Cumming, Georgia, 30041

  • 1106

    Daytona Beach, Florida, 32117

  • 1107

    Edgewater, Florida, 32132

  • 1134

    Elmer, New Jersey, 08318

  • 149

    Fort Wayne, Indiana, 90720

  • 1016

    Fort Worth, Texas, 76104

  • 1121

    Fremont, California, 94538

  • 1077

    Gilbert, Arizona, 85297

  • 1133

    Haddon Heights, New Jersey, 08035

  • 1031

    Hershey, Pennsylvania, 17033-0850

  • 1032

    Hialeah, Florida, 33016

  • 1017

    Houston, Texas, 77017

  • 1062

    Jackson, Tennessee, 38301

  • 1099

    Kansas City, Missouri, 64111

  • 166

    Lansing, Michigan, 48912

  • 101

    Littleton, Colorado, 80120

  • 117

    Lynchburg, Virginia, 24501

  • 137

    Macon, Georgia, 31201

  • 1012

    Memphis, Tennessee, 38104

  • 1026

    Miami, Florida, 33157

  • 1055

    Miami, Florida, 33176

  • 1008

    Monroe, Louisiana, 71201

  • 1079

    Mount Airy, North Carolina, 27030

  • 1064

    Naples, Florida, 34102

  • 114

    New York, New York, 10021

  • 1071

    North Miami Beach, Florida, 33162

  • 1086

    Oklahoma City, Oklahoma, 73135

  • 1009

    Orlando, Florida, 32803

  • 1045

    Peoria, Illinois, 61602

  • 1048

    Plano, Texas, 75093

  • 122

    Rapid City, South Dakota, 57701

  • 1076

    Richmond, Virginia, 23235

  • 0116

    Richmond, Virginia, 23298

  • 1004

    Riverton, Utah, 84096

  • 119

    Rochester, Minnesota, 55902

  • 1060

    Saint Augustine, Florida, 32086

  • 1093

    Saint Paul, Minnesota, 55101

  • 1007

    Salisbury, Maryland, 21804

  • 1014

    San Antonio, Texas, 78220

  • 1021

    Southampton, New York, 11968

  • 1035

    Stanford, California, 94305

  • 1018

    Statesville, North Carolina, 28625

  • 1066

    Trumbull, Connecticut, 06611

  • 1023

    Vista, California, 92083

  • 1025

    West Des Moines, Iowa, 50266

  • 1083

    West Hills, California, 91307

  • 1082

    Wyomissing, Pennsylvania, 19610

  • 105

    Yardley, Pennsylvania, 19067

  • 1097

    York, Pennsylvania, 17403

Other trials in United States

Brazil21 sites

  • 5221

    Belo Horizonte, REG1, 30110-934

  • 5228

    Belo Horizonte, 30150-320

  • 5217

    Brasília, REG1, 70390903

  • 5215

    Campinas, REG1, 13060-080

  • 5202

    Campinas, 13010-001

  • 5222

    Canoas, REG1, 92425

  • 5207

    Curitiba, REG1, 80320-320

  • 5201

    Goiânia, 74210-050

  • 5229

    Jaú, 17201130

  • 5227

    Juiz de Fora, REG1, 36033-318

  • 5209

    Recife, REG1, 50100060

  • 5235

    Rio de Janeiro, 20241-180

  • 5214

    Salvador, REG1, 40320-010

  • 5219

    Santo André, REG1, 09030-010

  • 5212

    São José do Rio Preto, REG1, 15015-210

  • 5220

    São Paulo, REG1, 01506-000

  • 5225

    São Paulo, REG1, 08270-070

  • 5232

    São Paulo, 05403-000

  • 5204

    Tatuí, 18270-170

  • 5205

    Uberlândia, REG1, 38411-186

  • 5231

    Votuporanga, 15500-003

Other trials in Brazil

Argentina18 sites

  • 5129

    Buenos Aires, 1425

  • 5125

    Buenos Aires, C1013AAB

  • 5106

    Ciudad Autonoma de Buenos Aires, Buenos Aires, 1428

  • 5117

    Ciudad Autonoma de Buenos Aires, Buenos Aires, 1430

  • 5116

    Córdoba, 5000

  • 5123

    Córdoba, 5000

  • 5118

    Córdoba, X5003DCE

  • 5134

    Corrientes, 3400

  • 5102

    La Plata, 1900

  • 5112

    Mar del Plata, Buenos Aires, B7600FYK

  • 5105

    Mar del Plata, Buenos Aires, B7600FZN

  • 5115

    Quilmes, Buenos Aires, B1878DVB

  • 5122

    Ramos Mejía, Buenos Aires, B1704ETD

  • 5132

    Rosario, 2000

  • 5109

    Salta, 4400

  • 5130

    San Nicolás, B2900DPA

  • 5110

    San Nicolás de los Arroyos, Buenos Aires, 2900

  • 5124

    Temperley, 1834

Other trials in Argentina

Canada18 sites

  • 215

    Cambridge, Ontario, N1R 6V6

  • 2011

    Greenfield Park, Quebec, J4V 2G8

  • 202

    Hamilton, Ontario, L8L 0A6

  • 2017

    Kelowna, British Columbia, V1Y 1T2

  • 2020

    Lévis, Quebec, G6V 4Z5

  • 205

    Montreal, Quebec, H2X 0A9

  • 203

    Montreal, Quebec

  • 2010

    North Vancouver, British Columbia, V7M 2H4

  • 2006

    Oshawa, Ontario, L1J 2K1

  • 2001

    Ottawa, Ontario, K1Y 4W7

  • 2014

    Québec, Quebec, G1R 2J6

  • 2002

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

  • 2003

    Saint-Jérôme, Quebec, J7Z 5T3

  • 2019

    Saskatoon, British Columbia, S7N 0W8

  • 201

    Sherbrooke, Quebec, J1H 5N4

  • 2018

    Surrey, British Columbia, V3V 0C6

  • 212

    Vancouver, British Columbia, V5Z 1M9

  • 213

    Victoria, British Columbia, V8T 1Z4

Other trials in Canada

Colombia6 sites

  • 5409

    Armenia, 630004

  • 5404

    Barranquilla, 80020

  • 5408

    Bucaramanga, 680002

  • 5401

    Medellín, 050034

  • 5407

    Punta de Cartagena, 130013

  • 5403

    San Gil, 684031

Other trials in Colombia

About this study

Official title: The NODE-303 Study: Multi-Centre, Multi-National,Open Label, Safety Study of Etripamil Nasal Spray for Patients With Paroxysmal Supraventricular Tachycardia.

NODE-303 was a multi-center, open label study to evaluate the safety of etripamil NS in participants with Paroxysmal Supraventricular Tachycardia (PSVT). Participants were provided with an ambulatory Cardiac Monitoring System (CMS) to help document PSVT episodes. The CMS was self-applied by the participant, when they felt the onset of PSVT symptoms. Participants self-administered etripamil NS if vagal maneuver was ineffective. After an episode of PSVT where study drug was administered, the participant returned to the investigative site and had the option to continue in NODE-303 and manage up to three subsequent episodes of PSVT with etripamil NS for a maximum of four episodes.

Read the detailed description

NODE-303 was a multi-center, open label study to evaluate the safety of etripamil NS in participants with PSVT. Participants were provided with an ambulatory CMS to help document PSVT episodes. The CMS was self-applied by the participant, when they felt the onset of PSVT symptoms. Participants self-administered etripamil NS 70 mg if vagal maneuver (VM) was ineffective. Approximately 2 years after study initiation, a protocol amendment was implemented to allow participants to administer a second dose of etripamil 70 mg 10 minutes after the first dose, if PSVT symptoms persisted. After an episode of PSVT where study drug was administered, the participant returned to the investigative site and had the option to continue in NODE-303 and manage up to three subsequent episodes of PSVT with etripamil NS for a maximum of four episodes.

The study included:

A Screening Visit during which the Investigator verified that the participant met the eligibility criteria of the NODE-303 study, obtained the signed informed consent, took blood and urine for laboratory evaluations, and conducted other screening procedures. The informed consent for NODE-303 was applicable for the initial and all subsequent PSVT episodes. A Baseline Visit during which the site confirmed eligibility, concomitant medications, trained the participant on study procedures, and gave the participant study drug, participant reported outcome (PRO) materials, and the CMS materials. A Treatment Period during which the participant completed the monthly PRO survey, self-identified symptoms of PSVT, used the CMS during 60 minutes, performed a VM, and self-administered etripamil NS if the symptoms did not resolve after the VM. Participants could be contacted during this period for reminders and training on what to do during a PSVT episode. Participants also completed a per episode survey after any PSVT episode they experience. During the Treatment Period, Follow-up Visits occurred at the study site up to 14 days after each episode of PSVT treated with etripamil NS, and during which the Investigator evaluated the results of the last usage of etripamil NS and reassessed participant's eligibility to continue in the study based on study inclusion and exclusion criteria. Participants who were eligible to continue in the study received additional study medication.

A Final Study Visit occurred when a participant discontinued or withdrew from the study, or when the overall study was completed, or the participant had completed the maximum number of doses. NODE-303 continued until enough documented self-administrations of etripamil NS were included in the safety database to meet regulatory requirements for the etripamil NS development program. The common study end date (CSED) for the entire study depended on the rate of accrual of the primary endpoint, unique participants with an episode. When the criteria for concluding the study were met, the Sponsor announced the CSED for the entire study and sites were informed in advance to schedule all final participant visits prior to the CSED.

Being tested
Etripamil NS
Keywords
PSVT
Medical subject headings
Tachycardia, Ventricular

What participants receive

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

  • Etripamil NSDrug

    Also called MSP-2017

    Participants were provided with an ambulatory Cardiac Monitoring System (CMS) to help document PSVT episodes. The CMS was self-applied by the participant, when PSVT symptoms begin. Participants self-administered etripamil NS if vagal maneuver was ineffective. After implementation of protocol amendment 2.1, participants had the option to administer a second dose of etripamil 70 mg 10 minutes after the first dose, if symptoms persisted. After an episode of PSVT where drug was administered, the participant returned to the investigative site for a study visit and was given the option to continue in NODE-303 and manage up to three subsequent episodes of PSVT with etripamil NS for a maximum of four episodes.

Study groups in NCT04072835
Study groupRoleWhat they receive
Etripamil NSExperimentalParticipants self-administered etripamil NS 70 mg. After implementation of protocol amendment 2.1 (16 March 2021), participants had the option to administer a second dose of etripamil 70 mg 10 minutes after the first dose, if PSVT symptoms persisted
Receives: Drug: Etripamil NS
Not TreatedNo interventionParticipants not treated with etripamil NS for a PSVT episode.

What is being measured

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

  1. Number of Participants With Adverse Events for Self-administered Etripamil NS Outside of the Clinical Setting.

    Number of participants with any adverse events experienced from baseline up to the final study visit including the treatment of up to 4 perceived PSVT episodes.

    Measured: From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months.

Secondary outcomes (1)

  1. Time to Conversion

    Kaplan-Meier estimates of time to conversion up to 60 minutes after etripamil administration for adjudicated conversion of confirmed episodes of PSVT to SR (Sinus Rhythm) reported at Follow-up Visit 1.

    Measured: Time to conversion up to 60 minutes after etripamil administration.

Timeline

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

  1. First posted28 Aug 2019
  2. Study start23 Sep 2019
  3. Primary completion26 Jan 2023
  4. Study completion26 Jan 2023

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
1,116 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04072835
Sponsor's protocol ID
NODE-303
Status last verified
May 2024
First submitted
15 Aug 2019
Last updated
23 May 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Dorian P, Alings M, Coutu B, Ip JE, Martinez FA, Piccini JP, Stambler BS, Sheikh M, Shardonofsky S, Bharucha DB, Camm AJ. Self-Administered Etripamil Nasal Spray Slows Ventricular Rate in Patients With Atrial Fibrillation: A Post Hoc Analysis of the NODE-303 Study. J Cardiovasc Electrophysiol. 2026 Apr;37(4):859-863. doi: 10.1111/jce.70287. Epub 2026 Feb 10.

    PubMed 41668514

  • Ip JE, Coutu B, Ip JH, Noseworthy PA, Parody ML, Rafii F, Sears SF, Singh N, Stambler BS, Tahirkheli NK, Agudelo-Uribe J, Hu D, Shardonofsky S, Sheikh MB, Holz A, Bharucha DB, Camm AJ. Etripamil Nasal Spray for Recurrent Paroxysmal Supraventricular Tachycardia Conversion: Results From the NODE-303 Open-Label Study. J Cardiovasc Electrophysiol. 2025 Nov;36(11):2990-3003. doi: 10.1111/jce.70086. Epub 2025 Sep 11.

    PubMed 40931676

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Etripamil NS in people with Paroxysmal Supraventricular Tachycardia, run by Milestone Pharmaceuticals Inc. at 124 sites in 5 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 6 inclusion and 19 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: finished, as of the sponsor's last update on 23 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 124 sites in United States, Brazil, Argentina, Canada, Colombia. 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. 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 23 May 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?

Number of Participants With Adverse Events for Self-administered Etripamil NS Outside of the Clinical Setting. (time frame: From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months.). 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 NCT04072835, which also lists 2 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 23 May 2024.

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