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ReVeRA-201: Etripamil in Atrial Fibrillation, Phase 2

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04467905
Recruitment Status : Recruiting
First Posted : July 13, 2020
Last Update Posted : January 25, 2022
Sponsor:
Collaborator:
The Montreal Health Innovations Coordinating Center (MHICC)
Information provided by (Responsible Party):
Milestone Pharmaceuticals Inc.

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

Condition or disease Intervention/treatment Phase
Atrial Fibrillation Drug: Etripamil Drug: Placebo Phase 2

Detailed Description:

This is a multi-center, randomized, double-blind, placebo-controlled study to evaluate the effects of etripamil Nasal Spray in patients with atrial fibrillation (AF). This study includes Screening, the Treatment Period and Follow-up procedures.

Each patient will receive placebo or 70 mg of etripamil intranasally; treatment will be randomized in a 1:1 ratio, to yield 50 evaluable patients with atrial fibrillation in 2 groups of 25.

Patients with atrial fibrillation (AF) will be selected by the Investigator. The screening procedures will include a review of inclusion/exclusion criteria and recording of any concomitant medications.

After screening procedures are complete, eligible patients will be randomized to receive etripamil or placebo. Heart rate will be measured via Holter ECG (Electrocardiogram)10 minutes prior to and immediately before drug administration; patients must exhibit a rapid ventricular rate (≥110 bpm measured during 1 minute) prior to drug administration in order to be dosed. Blinded study drug will be administered during Holter ECG (Electrocardiogram) monitoring, which will be conducted for at least 10 minutes prior to and for 6 hours after administration.

Patients will undergo a safety follow-up assessment and return the Holter device approximately 24 hours post-dose. Patients will also be contacted by phone 7 days post-dosing for safety follow-up.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multi-Centre, Placebo-Controlled, Phase 2 Study of Etripamil Nasal Spray (NS) for the Reduction of Ventricular Rate in Patients With Atrial Fibrillation.
Actual Study Start Date : November 19, 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Patients will receive a total of 200 μL of placebo ((i.e. 100 μL in each nostril) via the Aptar Pharma Nasal Spray Bidose System. The devices will be prefilled and packaged. Instructions on device usage will be provided.
Drug: Placebo
The formulation of placebo will consist of water, sodium acetate, disodium, disodium ethylene-diamine-tetra-acetic acid (EDTA), and sulfuric acid to reproduce the same pH as the etripamil formulation.

Experimental: Etripamil
Patients will receive a total of 200 μL of etripamil Nasal spray 70 mg via the Aptar Pharma Nasal Spray Bidose System. The devices will be prefilled and packaged. Instructions on device usage will be provided.
Drug: Etripamil
The formulation of etripamil Nasal Spray will consist 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.




Primary Outcome Measures :
  1. The maximum reduction in ventricular rate, measured on Holter monitoring, within 60 minutes from drug administration. [ Time Frame: 60 minutes post drug administration ]

Secondary Outcome Measures :
  1. The elapsed time from drug administration to nadir (lowest average heart rate) in the 60 minutes post drug administration. [ Time Frame: 60 minutes post drug administration ]
  2. The percentage of patients achieving ventricular rate of <100 bpm in the 60 minutes post drug administration. [ Time Frame: 60 minutes post drug administration ]
  3. The percentage of patients with 10% reduction from baseline ventricular rate in the 60 minutes post drug administration. [ Time Frame: 60 minutes post drug administration ]
  4. The percentage of patients with 20% reduction from baseline ventricular rate in the 60 minutes post drug administration. [ Time Frame: 60 minutes post drug administration ]
  5. The percentage of patients cardioverting into sinus rhythm (for at least 30 seconds) in the 60 minutes post drug administration. [ Time Frame: 60 minutes post drug administration ]
  6. Rating of Treatment Satisfaction Questionnaire for Medication (TSQM). [ Time Frame: 60 minutes post drug administration ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A patient will be eligible for study participation if they meet all of the following criteria:

  1. Aged 18 years and over.
  2. Has provided written informed consent.
  3. Patients with episodes of paroxysmal, persistent or permanent AF (Atrial Fibrillation), presenting with AF and a ventricular rate ≥110 bpm, measured over 1 minute on an ECG.
  4. Patients should receive appropriate antithrombotic therapy as per Canadian Cardiovascular Society (CCS) guidelines:

    1. Etripamil (a calcium channel blocker) is intended for acute rate control only. If rhythm control is desired (outside of the present protocol), anticoagulation as per CCS guidelines may start after the administration of study drug.

Exclusion Criteria:

A patient will be excluded from the study if they meet any of the following criteria:

  1. Has evidence of atrial flutter (ECG) at presentation.
  2. Has a history of stroke,Transient Ischemic Attack (TIA) or peripheral embolism within the last 3 months.
  3. Has 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. Has 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. Has a history of second- or third-degree atrioventricular block.
  9. Regular rhythm suggesting a complete Atrioventricular (AV) block.
  10. Has 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 patient was successfully revascularized.
  12. Positive pregnancy test result at screening, and females of childbearing potential who do not agree to use adequate method of contraception for the duration of the study.
  13. Has evidence of any clinically significant acute or chronic condition of the nasal cavity (e.g., rhinitis or deviated septum) which could interfere with administration of the study drug in either or both nasal cavities.
  14. Has a history of sensitivity to verapamil.
  15. Has previously participated in a clinical study for etripamil.
  16. Has a history of sensitivity to any components of the investigational product.
  17. Signs of alcohol or drug intoxication at the time of presentation which, in the opinion of the Investigator, would impact the validity of study results.
  18. Is currently participating in another drug or device study, or has received an investigational drug or device within 30 days of Screening.
  19. Has 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 jeopardize the safety of the patient or impact the validity of study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04467905


Contacts
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Contact: Douglas Wight, MSc +1-514-336-0444 ext 225 dwight@milestonepharma.com
Contact: Francis Plat, M.D +1-514-336-0444 ext 226 fplat@milestonepharma.com

Locations
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Canada, Quebec
CIUSSS de l'Estrie-Centre Haute-Yamaska - Hôpital de Granby Recruiting
Granby, Quebec, Canada, J2G 1T7
CISSS de Laval - Cité-de-la-Santé Recruiting
Laval, Quebec, Canada, H7M 3L9
Institut de Cardiologie de Montreal Recruiting
Montréal, Quebec, Canada, H1T 1C8
CHU Montréal Recruiting
Montréal, Quebec, Canada, H2X 0A9
CIUSSS du Nord-de-l'Île-de-Montréal - Hôpital du Sacré-Cœur Recruiting
Montréal, Quebec, Canada, H4J 1C5
CHU de Québec-Université Laval - Hôtel Dieu de Québec Recruiting
Québec, Quebec, Canada, G1R 2J6
CISSS Bas-Saint-Laurent / Hôpital de Rimouski Recruiting
Rimouski, Quebec, Canada, G5L 5T1
CISSS des Laurentides / Unité de recherche clinique Recruiting
Saint-Jérôme, Quebec, Canada, J7Z 5T3
CIUSSS de l'Estrie - CHU Recruiting
Sherbrooke, Quebec, Canada, J1H 5N4
CISSS de Lanaudière - Hôpital Pierre-Le Gardeur Recruiting
Terrebonne, Quebec, Canada, J6V 2H2
CIUSSS Mauricie-Centre-du-Québec - CHAUR Recruiting
Trois-Rivières, Quebec, Canada, G8Z 3R9
Sponsors and Collaborators
Milestone Pharmaceuticals Inc.
The Montreal Health Innovations Coordinating Center (MHICC)
Investigators
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Principal Investigator: Denis Roy, M.D Montreal Heart Institute (MHI)
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Responsible Party: Milestone Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT04467905    
Other Study ID Numbers: MSP-2017-5001
First Posted: July 13, 2020    Key Record Dates
Last Update Posted: January 25, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Milestone Pharmaceuticals Inc.:
atrial fibrillation
ventricular rate control
rapid ventricular rate
etripamil
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Etripamil
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs