ReVeRA-201: Etripamil in Atrial Fibrillation, Phase 2
- Registration Number
- NCT04467905
- Lead Sponsor
- Milestone Pharmaceuticals Inc.
- Brief Summary
Many patients with atrial fibrillation 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).
- 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 (Screening and Treament Period occur on the same day) 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 obtaining informed consent, a review of inclusion/exclusion criteria, a complete physical examination, 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) on the Holter report prior to drug administration in order to receive the study drug. 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, patient discharged after 60 minutes if clinically warranted.
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 69
A patient will be eligible for study participation if they meet all of the following criteria:
-
Aged 18 years and over.
-
Has provided written informed consent.
-
Patients with episodes of paroxysmal, persistent or permanent AF (Atrial Fibrillation), presenting with AF and a ventricular rate ≥110 bpm, measured over 1 minute
-
Patients should receive 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) is intended for acute rate control only. If rhythm control is desired (outside of the present protocol), anticoagulation as per guidelines may start after the administration of study drug.
A patient will be excluded from the study if they meet any of the following criteria:
- Has evidence of atrial flutter (ECG) at presentation.
- Has a history of stroke,Transient Ischemic Attack (TIA) or peripheral embolism within the last 3 months.
- 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.
- 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).
- 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.
- Has a history of second- or third-degree atrioventricular block.
- Regular rhythm suggesting a complete Atrioventricular (AV) block.
- Has 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 patient was successfully revascularized.
- 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.
- 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.
- Has a history of sensitivity to verapamil.
- Has previously participated in a clinical study for etripamil.
- Has a history of sensitivity to any components of the investigational product.
- 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.
- Is currently participating in another drug or device study, or has received an investigational drug or device within 30 days of Screening.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Administration of placebo at the emergency department for an episode of atrial fibrillation Etripamil Etripamil Administration of 70 mg etripamil at the emergency department for an episode of atrial fibrillation
- Primary Outcome Measures
Name Time Method The Maximum Reduction in Ventricular Rate, Measured on Holter Monitoring, Within 60 Minutes From Drug Administration. 60 minutes post 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (18)
Treant Zorggroep
🇳🇱Emmen, Netherlands
Jeroen Bosch Ziekenhuis Rijnstate Ziekenhuis
🇳🇱Arnhem, Netherlands
Slingeland Ziekenhuis
🇳🇱Doetinchem, Netherlands
Hamilton Health Science
🇨🇦Hamilton, Ontario, Canada
CISSS de Lanaudière - Hôpital Pierre-Le Gardeur
🇨🇦Terrebonne, Quebec, Canada
Gelre Ziekenhuizen
🇳🇱Zutphen, Netherlands
Jeroen Bosch Ziekenhuis
🇳🇱Den Bosch, Netherlands
CHU Montréal
🇨🇦Montréal, Quebec, Canada
Institut de Cardiologie de Montreal
🇨🇦Montréal, Quebec, Canada
CISSS Bas-Saint-Laurent / Hôpital de Rimouski
🇨🇦Rimouski, Quebec, Canada
Franciscus Gasthuis
🇳🇱Rotterdam, Netherlands
CIUSSS du Nord-de-l'Île-de-Montréal - Hôpital du Sacré-Cœur
🇨🇦Montréal, Quebec, Canada
QEII HSC - Nova Scotia Health Authority
🇨🇦Halifax, Nova Scotia, Canada
CISSS des Laurentides / Unité de recherche clinique
🇨🇦Saint-Jérôme, Quebec, Canada
PACE (Partners in Advanced Cardiac Evaluation)
🇨🇦Newmarket, Ontario, Canada
Elkerliek Ziekenhuis
🇳🇱Helmond, Netherlands
CIUSSS de l'Estrie - CHU
🇨🇦Sherbrooke, Quebec, Canada
Ottawa Hospital General & Civic Campus Research Institute
🇨🇦Ottawa, Ontario, Canada