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Atrial FibrillationPhase 2NCT04467905

ReVeRA-201: Etripamil in Atrial Fibrillation, Phase 2

A Phase 2 study testing Etripamil in people with Atrial Fibrillation, run by Milestone Pharmaceuticals Inc. at 18 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Atrial Fibrillation
What is being tested?
Etripamil
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
69 participants
Where
18 sitesin 2 countries
Study dates
19 Nov 2020to 10 Aug 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • Had previously participated in a clinical study for etripamil.
  • Had a history of sensitivity to any components of the investigational product.
  • 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.
  • Was participating in another drug or device study, or had received an investigational drug or device within 30 days of Screening.
  • 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.

Trial locations and contacts

18 sites in 2 countries.

18 sites in 2 countries

Canada11 sites

  • QEII HSC - Nova Scotia Health Authority

    Halifax, Nova Scotia, B3H 3A7

  • Hamilton Health Science

    Hamilton, Ontario, L2L 2X2

  • Institut de Cardiologie de Montreal

    Montreal, Quebec, H1T 1C8

  • CHU Montréal

    Montreal, Quebec, H2X 0A9

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

    Montreal, Quebec, H4J 1C5

  • PACE (Partners in Advanced Cardiac Evaluation)

    Newmarket, Ontario, L3Y 2P6

  • Ottawa Hospital General & Civic Campus Research Institute

    Ottawa, Ontario, K1Y4E9

  • CISSS Bas-Saint-Laurent / Hôpital de Rimouski

    Rimouski, Quebec, G5L 5T1

  • CISSS des Laurentides / Unité de recherche clinique

    Saint-Jérôme, Quebec, J7Z 5T3

  • CIUSSS de l'Estrie - CHU

    Sherbrooke, Quebec, J1H 5N4

  • CISSS de Lanaudière - Hôpital Pierre-Le Gardeur

    Terrebonne, Quebec, J6V 2H2

Other trials in Canada

Netherlands7 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch, 5223 GZ

  • Jeroen Bosch Ziekenhuis Rijnstate Ziekenhuis

    Arnhem, 6815 AD

  • Slingeland Ziekenhuis

    Doetinchem, 7009 BL

  • Treant Zorggroep

    Emmen, 7824 AA

  • Elkerliek Ziekenhuis

    Helmond, 5707 HA

  • Franciscus Gasthuis

    Rotterdam, 3045 PM

  • Gelre Ziekenhuizen

    Zutphen, 7207 AE

Other trials in Netherlands

About this study

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.

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.

Read the 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.

Being tested
Etripamil, Placebo
Keywords
atrial fibrillation, ventricular rate control, rapid ventricular rate, etripamil
Medical subject headings
Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EtripamilDrug

    Also called MSP-2017

    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.

  • PlaceboDrug

    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.

Study groups in NCT04467905
Study groupRoleWhat they receive
PlaceboPlacebo comparatorAdministration of placebo at the emergency department for an episode of atrial fibrillation
Receives: Drug: Placebo
EtripamilExperimentalAdministration of 70 mg etripamil at the emergency department for an episode of atrial fibrillation
Receives: Drug: Etripamil

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 60 minutes post drug administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2020
  2. Study start19 Nov 2020
  3. Primary completion3 Aug 2023
  4. Study completion10 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04467905
Sponsor's protocol ID
MSP-2017-5001
Status last verified
Aug 2024
First submitted
8 Jul 2020
Last updated
19 Sep 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37950726

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Etripamil in people with Atrial Fibrillation, run by Milestone Pharmaceuticals Inc. at 18 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Canada, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Maximum Reduction in Ventricular Rate, Measured on Holter Monitoring, Within 60 Minutes From Drug Administration. (time frame: 60 minutes post drug administration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04467905, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.

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