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

NCT04072835 | Completed Phase 3 Results FDA Drug

• 1 other identifier: NODE-303
• Study Type: interventional
• Target: 1,116
• Locations: 5 countries
• Sites: 124

Brief 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. 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.

Conditions

Paroxysmal Supraventricular Tachycardia

Keywords

PSVT

Outcome Measures

Primary Outcomes (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.

  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)

• Time to Conversion

  Time to conversion up to 60 minutes after etripamil administration.

Study Arms (2)

Etripamil NS

EXPERIMENTAL

Participants 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

Drug: Etripamil NS

Not Treated

NO INTERVENTION

Participants not treated with etripamil NS for a PSVT episode.

Interventions

Etripamil NS DRUG

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.

Also known as: MSP-2017

Etripamil NS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Milestone Pharmaceuticals Inc.: lead
• IQVIA Biotech: collaborator

Study Sites (124)

1077

Gilbert, Arizona, 85297, United States

Location

1121

Fremont, California, 94538, United States

Location

1035

Stanford, California, 94305, United States

Location

1023

Vista, California, 92083, United States

Location

1083

West Hills, California, 91307, United States

Location

101

Littleton, Colorado, 80120, United States

Location

1010

Bridgeport, Connecticut, 06610, United States

Location

1066

Trumbull, Connecticut, 06611, United States

Location

1042

Bradenton, Florida, 34208, United States

Location

1106

Daytona Beach, Florida, 32117, United States

Location

1107

Edgewater, Florida, 32132, United States

Location

1032

Hialeah, Florida, 33016, United States

Location

1026

Miami, Florida, 33157, United States

Location

1055

Miami, Florida, 33176, United States

Location

1064

Naples, Florida, 34102, United States

Location

1071

North Miami Beach, Florida, 33162, United States

Location

1009

Orlando, Florida, 32803, United States

Location

1060

Saint Augustine, Florida, 32086, United States

Location

1022

Cumming, Georgia, 30041, United States

Location

137

Macon, Georgia, 31201, United States

Location

1115

Coeur d'Alene, Idaho, 83814, United States

Location

1045

Peoria, Illinois, 61602, United States

Location

149

Fort Wayne, Indiana, 90720, United States

Location

1025

West Des Moines, Iowa, 50266, United States

Location

1008

Monroe, Louisiana, 71201, United States

Location

1007

Salisbury, Maryland, 21804, United States

Location

1078

Boston, Massachusetts, 02215, United States

Location

166

Lansing, Michigan, 48912, United States

Location

119

Rochester, Minnesota, 55902, United States

Location

1093

Saint Paul, Minnesota, 55101, United States

Location

1099

Kansas City, Missouri, 64111, United States

Location

1134

Elmer, New Jersey, 08318, United States

Location

1133

Haddon Heights, New Jersey, 08035, United States

Location

114

New York, New York, 10021, United States

Location

1021

Southampton, New York, 11968, United States

Location

129

Charlotte, North Carolina, 28204, United States

Location

1065

Charlotte, North Carolina, 28277, United States

Location

1079

Mount Airy, North Carolina, 27030, United States

Location

1018

Statesville, North Carolina, 28625, United States

Location

1024

Canton, Ohio, 44710, United States

Location

123

Cincinnati, Ohio, 45242, United States

Location

142

Columbus, Ohio, 31904, United States

Location

1086

Oklahoma City, Oklahoma, 73135, United States

Location

1123

Corvallis, Oregon, 97330, United States

Location

1031

Hershey, Pennsylvania, 17033-0850, United States

Location

1082

Wyomissing, Pennsylvania, 19610, United States

Location

105

Yardley, Pennsylvania, 19067, United States

Location

1097

York, Pennsylvania, 17403, United States

Location

122

Rapid City, South Dakota, 57701, United States

Location

1062

Jackson, Tennessee, 38301, United States

Location

1012

Memphis, Tennessee, 38104, United States

Location

1047

Austin, Texas, 78705, United States

Location

1092

Austin, Texas, 78705, United States

Location

1016

Fort Worth, Texas, 76104, United States

Location

1017

Houston, Texas, 77017, United States

Location

1048

Plano, Texas, 75093, United States

Location

1014

San Antonio, Texas, 78220, United States

Location

1004

Riverton, Utah, 84096, United States

Location

117

Lynchburg, Virginia, 24501, United States

Location

1076

Richmond, Virginia, 23235, United States

Location

0116

Richmond, Virginia, 23298, United States

Location

5106

Ciudad Autonoma de Buenos Aires, Buenos Aires, 1428, Argentina

Location

5117

Ciudad Autonoma de Buenos Aires, Buenos Aires, 1430, Argentina

Location

5112

Mar del Plata, Buenos Aires, B7600FYK, Argentina

Location

5105

Mar del Plata, Buenos Aires, B7600FZN, Argentina

Location

5115

Quilmes, Buenos Aires, B1878DVB, Argentina

Location

5122

Ramos Mejía, Buenos Aires, B1704ETD, Argentina

Location

5110

San Nicolás de los Arroyos, Buenos Aires, 2900, Argentina

Location

5129

Buenos Aires, 1425, Argentina

Location

5125

Buenos Aires, C1013AAB, Argentina

Location

5134

Corrientes, 3400, Argentina

Location

5116

Córdoba, 5000, Argentina

Location

5123

Córdoba, 5000, Argentina

Location

5118

Córdoba, X5003DCE, Argentina

Location

5102

La Plata, 1900, Argentina

Location

5132

Rosario, 2000, Argentina

Location

5109

Salta, 4400, Argentina

Location

5130

San Nicolás, B2900DPA, Argentina

Location

5124

Temperley, 1834, Argentina

Location

5221

Belo Horizonte, REG1, 30110-934, Brazil

Location

5217

Brasília, REG1, 70390903, Brazil

Location

5215

Campinas, REG1, 13060-080, Brazil

Location

5222

Canoas, REG1, 92425, Brazil

Location

5207

Curitiba, REG1, 80320-320, Brazil

Location

5227

Juiz de Fora, REG1, 36033-318, Brazil

Location

5209

Recife, REG1, 50100060, Brazil

Location

5214

Salvador, REG1, 40320-010, Brazil

Location

5219

Santo André, REG1, 09030-010, Brazil

Location

5212

São José do Rio Preto, REG1, 15015-210, Brazil

Location

5220

São Paulo, REG1, 01506-000, Brazil

Location

5225

São Paulo, REG1, 08270-070, Brazil

Location

5205

Uberlândia, REG1, 38411-186, Brazil

Location

5228

Belo Horizonte, 30150-320, Brazil

Location

5202

Campinas, 13010-001, Brazil

Location

5201

Goiânia, 74210-050, Brazil

Location

5229

Jaú, 17201130, Brazil

Location

5235

Rio de Janeiro, 20241-180, Brazil

Location

5232

São Paulo, 05403-000, Brazil

Location

5204

Tatuí, 18270-170, Brazil

Location

5231

Votuporanga, 15500-003, Brazil

Location

2017

Kelowna, British Columbia, V1Y 1T2, Canada

Location

2010

North Vancouver, British Columbia, V7M 2H4, Canada

Location

2019

Saskatoon, British Columbia, S7N 0W8, Canada

Location

2018

Surrey, British Columbia, V3V 0C6, Canada

Location

212

Vancouver, British Columbia, V5Z 1M9, Canada

Location

213

Victoria, British Columbia, V8T 1Z4, Canada

Location

215

Cambridge, Ontario, N1R 6V6, Canada

Location

202

Hamilton, Ontario, L8L 0A6, Canada

Location

2006

Oshawa, Ontario, L1J 2K1, Canada

Location

2001

Ottawa, Ontario, K1Y 4W7, Canada

Location

2011

Greenfield Park, Quebec, J4V 2G8, Canada

Location

2020

Lévis, Quebec, G6V 4Z5, Canada

Location

205

Montreal, Quebec, H2X 0A9, Canada

Location

203

Montreal, Quebec, Canada

Location

2014

Québec, Quebec, G1R 2J6, Canada

Location

2002

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

Location

2003

Saint-Jérôme, Quebec, J7Z 5T3, Canada

Location

201

Sherbrooke, Quebec, J1H 5N4, Canada

Location

5409

Armenia, 630004, Colombia

Location

5404

Barranquilla, 80020, Colombia

Location

5408

Bucaramanga, 680002, Colombia

Location

5401

Medellín, 050034, Colombia

Location

5407

Punta de Cartagena, 130013, Colombia

Location

5403

San Gil, 684031, Colombia

Location

Related Publications (1)

• 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.

  PMID: 40931676 DERIVED

MeSH Terms

Conditions

Tachycardia, Ventricular

Condition Hierarchy (Ancestors)

Tachycardia; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Cameron Szakacs _PhD_VP Drug Development
• Organization: Milestone Pharmaceuticals Inc.

cszakacs@milestonepharma.com

1 704-594-4102

Study Officials

• Francis Plat, MD

  Milestone Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2019
• First Posted: August 28, 2019
• Study Start: September 23, 2019
• Primary Completion: January 26, 2023
• Study Completion: January 26, 2023
• Last Updated: May 23, 2024
• Results First Posted: May 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (61); CO (6); BR (21); AR (18); CA (18)