ReVeRA-201: Etripamil in Atrial Fibrillation, Phase 2

NCT ID: NCT04467905

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-19
• Study Completion Date: 2023-08-10

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.

Detailed Description

This was a multi-center, randomized, double-blind, placebo-controlled study to evaluate the effects of etripamil nasal spray in participants with AF. This study included Screening, the Treatment Period (Screening and Treatment Period occur on the same day) and safety follow-up procedures.

Each participant received placebo or 70 mg of etripamil intranasally; treatment were randomized in a 1:1 ratio, to yield 50 evaluable participants with AF in 2 groups of 25.

Participants with AF were selected by the Investigator. The screening procedures included obtaining informed consent, a review of inclusion/exclusion criteria, a complete physical examination, and recording of any concomitant medications.

After screening procedures were complete, eligible participants were randomized to receive etripamil or placebo. Heart rate was measured continuously via Holter Electrocardiogram (ECG) from at least 10 minutes prior to dosing to 6 hours after study drug administration. Participants had to exhibit a rapid ventricular rate (≥110 bpm measured during 1 minute) on the Holter report prior to drug administration in order to receive the study drug. Beyond 60 minutes after study drug administration, medical care was offered in accordance with the standard of care and the participant was discharged from the clinic, while still wearing the Holter device.

Participants underwent a safety follow-up assessment and return the Holter device approximately 24 hours post-dose. Participants were contacted by phone 7 days post-dosing for safety follow-up.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Etripamil

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

Group Type: EXPERIMENTAL

Etripamil

Intervention Type: 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.

Interventions

Etripamil

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

MSP-2017

Eligibility Criteria

Inclusion Criteria

A participant was eligible for study participation if they met all of the following criteria:

1. Aged 18 years and over.

2. Provided written informed consent.

3. Participants with episodes of paroxysmal, persistent or permanent AF, presenting with AF and a ventricular rate ≥110 bpm, measured over 1 minute

4. 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).

1. 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.

Exclusion Criteria

A participant was excluded from the study if they met any of the following criteria:

1. Had evidence of atrial flutter (ECG) at presentation.

2. Had a history of stroke, transient ischemic attack (TIA) or peripheral embolism within the last 3 months.

3. 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.

4. 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).

5. Hemodynamic instability, with systolic blood pressure <90 mmHg or diastolic blood pressure <60 mmHg.

6. Known uncorrected severe aortic or mitral stenosis.

7. Hypertrophic cardiomyopathy with outflow tract obstruction.

8. Had a history of second- or third-degree atrioventricular block.

9. Regular rhythm suggesting a complete atrioventricular block.

10. Had a history or evidence of torsades de pointes, sick sinus syndrome, or Brugada syndrome.

11. Evidence of acute coronary syndrome within the last 12 months except if participant was successfully revascularized.

12. 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.

13. 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.

14. Had a history of sensitivity to verapamil.

15. Had previously participated in a clinical study for etripamil.

16. Had a history of sensitivity to any components of the investigational product.

17. Had signs of alcohol or drug intoxication at the time of presentation which, in the opinion of the Investigator, would have impacted the validity of study results.

18. Was participating in another drug or device study, or had received an investigational drug or device within 30 days of Screening.

19. Had evidence of clinically significant cardiovascular, endocrine, gastrointestinal, hematologic, hepatic, immunologic, neurologic, oncologic, pulmonary, psychiatric, or renal disease or any other condition which, in the opinion of the Investigator, would have jeopardized the safety of the participant or impacted the validity of study results.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Montreal Health Innovations Coordinating Center (MHICC)

OTHER

Sponsor Role: collaborator

JSS Medical Research Inc.

INDUSTRY

Sponsor Role: collaborator

Milestone Pharmaceuticals Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denis Roy, M.D

Role: PRINCIPAL_INVESTIGATOR

Montreal Heart Institute (MHI)

Locations

QEII HSC - Nova Scotia Health Authority

Halifax, Nova Scotia, Canada

Hamilton Health Science

Hamilton, Ontario, Canada

PACE (Partners in Advanced Cardiac Evaluation)

Newmarket, Ontario, Canada

Ottawa Hospital General & Civic Campus Research Institute

Ottawa, Ontario, Canada

Institut de Cardiologie de Montreal

Montreal, Quebec, Canada

CHU Montréal

Montreal, Quebec, Canada

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

Montreal, Quebec, Canada

CISSS Bas-Saint-Laurent / Hôpital de Rimouski

Rimouski, Quebec, Canada

CISSS des Laurentides / Unité de recherche clinique

Saint-Jérôme, Quebec, Canada

CIUSSS de l'Estrie - CHU

Sherbrooke, Quebec, Canada

CISSS de Lanaudière - Hôpital Pierre-Le Gardeur

Terrebonne, Quebec, Canada

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Jeroen Bosch Ziekenhuis Rijnstate Ziekenhuis

Arnhem, , Netherlands

Slingeland Ziekenhuis

Doetinchem, , Netherlands

Treant Zorggroep

Emmen, , Netherlands

Elkerliek Ziekenhuis

Helmond, , Netherlands

Franciscus Gasthuis

Rotterdam, , Netherlands

Gelre Ziekenhuizen

Zutphen, , Netherlands

Countries

Canada; Netherlands

References

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.

Reference Type: DERIVED

PMID: 37950726 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

MSP-2017-5001

Identifier Type: -

Identifier Source: org_study_id