ReVeRA-201: Etripamil in Atrial Fibrillation, Phase 2

NCT04467905 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: MSP-2017-5001
• Study Type: interventional
• Target: 69
• Locations: 2 countries
• Sites: 18

Brief Summary

Many patients with atrial fibrillation (AF) experience persistent tachycardia with episodes of rapid ventricular rate despite chronic treatment to reduce ventricular rate. The objectives of this study were to demonstrate the superiority of a nasal spray of etripamil over placebo in reducing ventricular rate in patients with AF; and to evaluate the safety and efficacy of etripamil nasal spray in participants with AF.

Conditions

Atrial Fibrillation

Keywords

atrial fibrillation; ventricular rate control; rapid ventricular rate; etripamil

Outcome Measures

Primary Outcomes (1)

• The Maximum Reduction in Ventricular Rate, Measured on Holter Monitoring, Within 60 Minutes From Drug Administration.

  Baseline ventricular rate is defined as the average heart rate over 5 minutes immediately prior to drug administration. Nadir is defined as the lowest moving average heart rate over 5 minutes recorded in the 60 minutes post drug administration.

  60 minutes post drug administration

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Administration of placebo at the emergency department for an episode of atrial fibrillation

Drug: Placebo

Etripamil

EXPERIMENTAL

Administration of 70 mg etripamil at the emergency department for an episode of atrial fibrillation

Drug: Etripamil

Interventions

Etripamil DRUG

The formulation of etripamil nasal spray consists of MSP-2017 (etripamil), water, acetic acid, disodium ethylene-diamine-tetra-acetic acid (EDTA), and sulfuric acid. The dose of etripamil to be evaluated in this study is 70 mg.

Also known as: MSP-2017

Etripamil

Placebo DRUG

The formulation of placebo nasal spray consists of water, sodium acetate, disodium, disodium ethylene-diamine-tetra-acetic acid (EDTA), and sulfuric acid to reproduce the same pH as the etripamil formulation.

Placebo

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:
• Aged 18 years and over.
• Provided written informed consent.
• Participants with episodes of paroxysmal, persistent or permanent AF, presenting with AF and a ventricular rate ≥110 bpm, measured over 1 minute
• Participants received appropriate antithrombotic therapy as per the applicable guidelines for atrial fibrillation management (e.g., Canadian Cardiovascular Society (CCS) guidelines / European Society of Cardiology (ESC) guidelines).
• Etripamil (a calcium channel blocker) was intended for acute rate control only. If rhythm control was desired (outside of the present protocol), anticoagulation as per guidelines could be started after the administration of study drug.

You may not qualify if:

• A participant was excluded from the study if they met any of the following criteria:
• Had evidence of atrial flutter (ECG) at presentation.
• Had a history of stroke, transient ischemic attack (TIA) or peripheral embolism within the last 3 months.
• Had received by IV route any of the following within one hour before study drug administration: flecainide, procainamide, digoxin, beta-blocker, or calcium channel blocker.
• Had signs and symptoms of severe congestive heart failure at presentation (e.g. tachypnea, oxygen desaturation \<90% unless due to known pulmonary disease, pulmonary rales, sign of peripheral hypoperfusion).
• Hemodynamic instability, with systolic blood pressure \<90 mmHg or diastolic blood pressure \<60 mmHg.
• Known uncorrected severe aortic or mitral stenosis.
• Hypertrophic cardiomyopathy with outflow tract obstruction.
• Had a history of second- or third-degree atrioventricular block.
• Regular rhythm suggesting a complete atrioventricular block.
• Had a history or evidence of torsades de pointes, sick sinus syndrome, or Brugada syndrome.
• Evidence of acute coronary syndrome within the last 12 months except if participant was successfully revascularized.
• Positive pregnancy test result at screening, and females of childbearing potential who did not agree to use adequate method of contraception for the duration of the study.
• Had evidence of any clinically significant acute or chronic condition of the nasal cavity (e.g., rhinitis or deviated septum) which could have interfered with administration of the study drug in either or both nasal cavities.
• Had a history of sensitivity to verapamil.

Sponsors & Collaborators

• Milestone Pharmaceuticals Inc.: lead
• The Montreal Health Innovations Coordinating Center (MHICC): collaborator
• JSS Medical Research Inc.: collaborator

Study Sites (18)

QEII HSC - Nova Scotia Health Authority

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Hamilton Health Science

Hamilton, Ontario, L2L 2X2, Canada

Location

PACE (Partners in Advanced Cardiac Evaluation)

Newmarket, Ontario, L3Y 2P6, Canada

Location

Ottawa Hospital General & Civic Campus Research Institute

Ottawa, Ontario, K1Y4E9, Canada

Location

Institut de Cardiologie de Montreal

Montreal, Quebec, H1T 1C8, Canada

Location

CHU Montréal

Montreal, Quebec, H2X 0A9, Canada

Location

CIUSSS du Nord-de-l'Île-de-Montréal - Hôpital du Sacré-Cœur

Montreal, Quebec, H4J 1C5, Canada

Location

CISSS Bas-Saint-Laurent / Hôpital de Rimouski

Rimouski, Quebec, G5L 5T1, Canada

Location

CISSS des Laurentides / Unité de recherche clinique

Saint-Jérôme, Quebec, J7Z 5T3, Canada

Location

CIUSSS de l'Estrie - CHU

Sherbrooke, Quebec, J1H 5N4, Canada

Location

CISSS de Lanaudière - Hôpital Pierre-Le Gardeur

Terrebonne, Quebec, J6V 2H2, Canada

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Jeroen Bosch Ziekenhuis Rijnstate Ziekenhuis

Arnhem, 6815 AD, Netherlands

Location

Slingeland Ziekenhuis

Doetinchem, 7009 BL, Netherlands

Location

Treant Zorggroep

Emmen, 7824 AA, Netherlands

Location

Elkerliek Ziekenhuis

Helmond, 5707 HA, Netherlands

Location

Franciscus Gasthuis

Rotterdam, 3045 PM, Netherlands

Location

Gelre Ziekenhuizen

Zutphen, 7207 AE, Netherlands

Location

Related Publications (1)

• Camm AJ, Piccini JP, Alings M, Dorian P, Gosselin G, Guertin MC, Ip JE, Kowey PR, Mondesert B, Prins FJ, Roux JF, Stambler BS, van Eck J, Al Windy N, Thermil N, Shardonofsky S, Bharucha DB, Roy D. Multicenter, Phase 2, Randomized Controlled Study of the Efficacy and Safety of Etripamil Nasal Spray for the Acute Reduction of Rapid Ventricular Rate in Patients With Symptomatic Atrial Fibrillation (ReVeRA-201). Circ Arrhythm Electrophysiol. 2023 Dec;16(12):639-650. doi: 10.1161/CIRCEP.123.012567. Epub 2023 Nov 11.

  PMID: 37950726 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

etripamil

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Leonid Kokovin-Sher
• Organization: Milestone Pharmaceuticals Inc.

lkokovin-sher@milestonepharma.com

1 450-912-6783

Study Officials

• Denis Roy, M.D

  Montreal Heart Institute (MHI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2020
• First Posted: July 13, 2020
• Study Start: November 19, 2020
• Primary Completion: August 3, 2023
• Study Completion: August 10, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (11); NL (7)