A Phase III Superiority Study of Vernakalant vs Amiodarone in Subjects With Recent Onset Atrial Fibrillation

NCT ID: NCT00668759

Last Updated: 2009-12-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 254 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2009-11-30

Brief Summary

The primary objective of the study is to demonstrate the superiority of vernakalant injection over amiodarone injection in the conversion of atrial fibrillation (AF) to sinus rhythm (SR) within 90 minutes of the start of drug administration. The secondary objective is to compare the safety of vernakalant to amiodarone.

Detailed Description

This is a double-blind, active-controlled, double-dummy, multi-center, randomized trial in subjects with symptomatic AF of 3 to 48 hours duration.

Subjects will be randomized to receive vernakalant injection or amiodarone injection in a 1:1 ratio.

Safety will be assessed through the monitoring of adverse events, vital signs, continuous telemetry monitoring, 12-lead Holter monitoring, 12-lead ECGs, and laboratory tests.

At 2 hours after the start of infusion, electrical cardioversion may be performed or rate control medication may be administered. Class I and Class III antiarrhythmics are not to be administered for 24 hours after the start of infusion.

Subjects are to remain in the clinic for at least 6 hours after the start of infusion. Subjects will attend a follow-up visit at 7 (±2) days after treatment and will receive a follow-up telephone call at 30 (±3) days for assessment of serious adverse events, concomitant medications related to serious adverse events, and recurrence of AF.

All roles were blinded with the exception of each site's designated unblinded personnel who were responsible for randomization and preparation, dispensation and accountability of the study medication.

Expanded Access was not available through this protocol.

Conditions

Atrial Fibrillation

Keywords

atrial fibrillation; atrial fib; AF

Study Design

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

Study Groups

1

Vernakalant Injection:

In one infusion line, subjects will receive a 10-minute infusion of vernakalant followed by a 15-minute observation period, followed by an additional 10-minute infusion of vernakalant if required (if the subject is still in AF). To maintain blinding, a 60-minute infusion of placebo (D5W) will be administered in a second infusion line, followed by a maintenance infusion of placebo for a minimum of an additional 60 minutes.

Group Type: EXPERIMENTAL

Vernakalant Injection

Intervention Type: DRUG

10-minute infusion of 3 mg/kg vernakalant injection followed by a 15-minute observation period, followed by an additional 10-minute infusion of 2 mg/kg of vernakalant if required (if the subject is still in AF).

2

Amiodarone Injection:

In one infusion line subjects will receive a 60-minute infusion of amiodarone followed by a maintenance infusion of amiodarone over an additional 60 minutes. To maintain blinding, a 10-minute infusion of placebo (normal saline) will be administered in a second infusion line, followed by a 15 minute observation period, followed by a 10 minute infusion of placebo if the subject is still in AF.

Group Type: ACTIVE_COMPARATOR

Amiodarone Injection:

Intervention Type: DRUG

60-minute infusion of 5 mg/kg amiodarone followed by a maintenance infusion of 50 mg amiodarone over an additional 60 minutes (equivalent to approximately 15 mg/kg over 24 hrs).

Interventions

Vernakalant Injection

10-minute infusion of 3 mg/kg vernakalant injection followed by a 15-minute observation period, followed by an additional 10-minute infusion of 2 mg/kg of vernakalant if required (if the subject is still in AF).

Intervention Type: DRUG

Amiodarone Injection:

60-minute infusion of 5 mg/kg amiodarone followed by a maintenance infusion of 50 mg amiodarone over an additional 60 minutes (equivalent to approximately 15 mg/kg over 24 hrs).

Intervention Type: DRUG

Other Intervention Names

RSD1235; Kynapid; Amiodarone; Cordarone

Eligibility Criteria

Inclusion Criteria

• Have symptomatic AF of 3 to 48 hours duration at baseline.
• Be eligible for cardioversion.
• Have adequate anticoagulation therapy for cardioversion in accordance with standard of practice as recommended by ACC/AHA/ESC guidelines [1].
• Be hemodynamically stable and have systolic blood pressure (BP) above 100 mmHg and less than 160 mmHg and diastolic BP less than 95 mmHg at screening and baseline.

Exclusion Criteria

• Known or suspected prolonged QT or uncorrected QT interval of >440 msec as measured at screening on a 12 lead ECG, familial long QT syndrome, or previous torsades de pointes, ventricular fibrillation; or sustained ventricular tachycardia (VT).
• Symptomatic bradycardia, sick sinus syndrome, or ventricular rate less than 50 beats per minute (bpm) as documented by 12-lead ECG at screening.
• A QRS interval >140 msec.
• Atrial flutter.
• Significant valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis.
• Documented previous episodes of second or third degree atrioventricular (AV) block.
• Had a myocardial infarction (MI), acute coronary syndrome or cardiac surgery within 30 days prior to entry into the study.
• Uncorrected electrolyte imbalance of serum potassium or magnesium. Both K+ and Mg2+ must be corrected prior to dosing.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Advanz Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Cardiome Pharma Corp.

Principal Investigators

Tomas Janota, MD

Role: PRINCIPAL_INVESTIGATOR

VFN III. interní klinika

Christian Torp-Pedersen, MD

Role: PRINCIPAL_INVESTIGATOR

Gentofte Amtssygehus - Kardiologisk afdeling

Rein Kolk, MD

Role: PRINCIPAL_INVESTIGATOR

Tartu University Hospital Heart Clinic

Etienne Aliot, MD

Role: PRINCIPAL_INVESTIGATOR

CHU de Nancy - Hopital Brabois, Service de Cardiologie

Stefan Hohnloser, MD

Role: PRINCIPAL_INVESTIGATOR

Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie

Heikki Huikuri, MD

Role: PRINCIPAL_INVESTIGATOR

Oulu University Hospital - Dept of Internal Medicine

Piotr Ponikowski, MD

Role: PRINCIPAL_INVESTIGATOR

Osrodek Chorob Serca, Klinika Kardiologii, IV Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej we Wroclawiu

Steen Juul-Moller, MD

Role: PRINCIPAL_INVESTIGATOR

Universitetssjukhuset MAS

Locations

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Royal Hobart Hospital Cardiology Research

Hobart, Tasmania, Australia

Launceston General Hospital Cardiac Research Unit

Launceston, Tasmania, Australia

Royal Perth Hospital Emergency Research

Perth, Western Australia, Australia

Kingston General Hospital

Kingston, Ontario, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

Hopital de la Cite-de-la-Sante

Laval, Quebec, Canada

Institut de Cardiologie de Montreal

Montreal, Quebec, Canada

Centre Hopitalier de L'Universite de Montreal - Hotel Dieu

Montreal, Quebec, Canada

McGill University Health Center The Montreal General Hospital

Montreal, Quebec, Canada

Centre de santé et de services sociaux du Sud de Lanaudière - Hôpital Pierre-Le Gardeur

Terrebonne, Quebec, Canada

Mestrska nemocnice Caslav

Čáslav, , Czechia

Nemocnice Kroměříž

Kroměříž, , Czechia

Nemocnice Kutna Hora s.r.o. Interni Oddeleni

Kutná Hora, , Czechia

Nemocnice Decin Internal Medicine

Nove Město, , Czechia

Fakultní nemocnice v Motole, KAR

Prague, , Czechia

Ustredni vojenska nemocnice Koronarni jednotka

Prague, , Czechia

VFN - III. Interni Klinika

Prague, , Czechia

Oblastni nemocnice Pribram Interni Oddeleni

Příbram, , Czechia

Nemocnice v Semilech Interní oddělení

Semily, , Czechia

Nemocnice Slaný Interní oddělení

Slaný, , Czechia

Nemocnice Tabor

Tábor, , Czechia

Uherskohradistska nemocnice

Uherské Hradiste, , Czechia

Gentofte Amtssygehus Kardiologisk afdeling

Hellerup, , Denmark

Herlev Amtssygehus, Kardiologisk

Herlev, , Denmark

Sygehus Vendsyssel Hjorring

Hjørring, , Denmark

Roskilde Amts Sygehus Køge

Køge, , Denmark

Regionshospitalet Silkeborg

Silkeborg, , Denmark

Viimsi Hospital, Heart Clinic

Haabneeme, , Estonia

Pärnu Hospital Department of Cardiology

Pärnu, , Estonia

East Tallinn Central Hospital-Clinic of Cardiology

Tallinn, , Estonia

Tartu University Hospital Heart Clinic

Tartu, , Estonia

Oulu University Hospital - Dept of Internal Medicine

Oulu, , Finland

Hopital Trousseau - Service de Cardiologie

Chambray-lès-Tours, , France

CHU de Nancy - Hopital Brabois - Service de Cardiologie

Nancy, , France

Hôpital Lariboisiere

Paris, , France

CHU de Strasbourg - Hopital Hautepierre - Service de Cardiologie

Strasbourg, , France

Charite Campus Mitte, Med. Klinik und Poliklinik mit Schwerpunkt Kardiologie und Angiologie

Berlin, , Germany

Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin

Berlin, , Germany

Herzzentrum Brandenburg in Bernau Innere Medizin

Bernau, , Germany

Universitätsklinikum Bonn, Med. Klinik und Poliklinik II

Bonn, , Germany

Klinikum der Universität Köln, Medizinische Klinik III

Cologne, , Germany

Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie

Frankfurt, , Germany

Universitatsklinikum Gottingen, Herzzentrum

Göttingen, , Germany

Martin-Luther Universitat Halle, Med. Klinik und Poliklinik III- Fachrichtung Kardiologie

Halle, , Germany

Klinik Hamburg Bambek Kardiologie

Hamburg, , Germany

Medizinisches Versorgungszentrum Prof. Mathey, Prof. Schofer GmbH

Hamburg, , Germany

Medizinische Klinik, Klinikum Hannover Nordstadt

Hanover, , Germany

Ambulantes Herzzentrum Kassel Innere Medizin

Kassel, , Germany

Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen, , Germany

Carl-von Basedow-Klinikum Merseburg

Merseburg, , Germany

Klinikum Pirna GmbH, Innere Medizin II, Kardiologie

Pirna, , Germany

Krankenhaus Reinbek, St. Adolf-Stift

Reinbek, , Germany

Robert-Bosch-Krankenhaus, Abt. Kardiologie / Pulmologie

Stuttgart, , Germany

Latvian Center of Cardiology, P. Stradins Clinical University Hospital

Riga, , Latvia

Kaunas Medical University Hospital - Department of Cardiology

Kaunas, , Lithuania

Klaipeda Seamen's Hospital

Klaipėda, , Lithuania

Vilnius University Hospital Santariskiu Clinic - Center of Cardiology and Angiology

Vilnius, , Lithuania

WCN - Department of Cardiology Rijnstate Ziekenhuls

Arnhem, , Netherlands

Catharina Ziekenhuis Eindhoven

Eindhoven, , Netherlands

Groene Hart Zeikenhhaus

Gouda, , Netherlands

WCN - Bethesda ziekenhuis

Hoogeveen, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

WCN - Canisius-Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

WCN - St. Franciscus Gasthuis

Rotterdam, , Netherlands

Oddzial Kardiologiczny Wielospecjalityczny Szpital Miejski im.

Bydgoszcz, , Poland

Szpital Miejski im. J. Brudzinskiego Oddzial Kardiologii

Gdynia, , Poland

Klinika Chorob Wewnetrznych z Oddzialem Farmakologii Klinicznej i Terapii Monitorowanej

Lodz, , Poland

Oddział Internistyczno-Kardiologiczny Samodzielny Publiczny Szpital Wojewódzki im. Jana Bożego w Lublinie

Lublin, , Poland

Okregowy Szpital Kolejowy w Lublinie Samodzielny

Lublin, , Poland

Oddzial Kardiologii Inwazyjnej Szpital Specjalistyczny im. E.Szczeklika w Tarnowie

Tarnów, , Poland

Oddział Kardiologiczno-Internistyczny Specjalistyczny Szpital Miejski im. Mikołaja Kopernika

Torun, , Poland

Specjalistyczny Szpital Miejski im. Mikołaja Kopernika

Torun, , Poland

III Klinika Chorob Wewnetrznych i Kardiologii

Warsaw, , Poland

Wojskowy Instytut Medyczny, CSK MON

Warsaw, , Poland

Klinika Kardiologii Zachowawczej Centralny Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji w Warszawie

Warsaw, , Poland

Osrodek Chorob Serca, Klinika Kardiologii, 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny

Wroclaw, , Poland

Clinical Center of Serbia, Institute of CV Diseases

Belgrade, , Serbia

"Dedinje" Cardiovascular Institute

Belgrade, , Serbia

Institute of Treatment and Reahabilitation 'Niska Banja'

Niška Banja, , Serbia

Clinical Center Zemun, Dept. of Cardiology

Zemun, , Serbia

Middle Slovak Institute of Cardiovascular Diseases (SUSCCH)

Banska Bysterica, , Slovakia

NsP Prievidza so sidlom v Bojniciah

Bojnice, , Slovakia

Slovensky ustav srdcovych a cevnych chorob

Bratislava, , Slovakia

ICU, Hospital Lipt. Mikulas

Liptovský Mikuláš, , Slovakia

FN - I. interna klinika

Nitra, , Slovakia

Liva - Central Military Hospital

Ružomberok, , Slovakia

Interna klinika FN Trnava, Fakultna nemocnica Trnava

Trnava, , Slovakia

Internal Dep. Hospital Žilina

Žilina, , Slovakia

Universitetssjukhuset MAS

Malmo, , Sweden

Universityetssjukhuset, Orebro

Örebro, , Sweden

Akademiska Sjukhuset, Uppsala

Uppsala, , Sweden

Donetsk Regional Clinical Hospital

Donetsk, , Ukraine

City Clinical Hospital #8

Kharkiv, , Ukraine

City Clinical Hospital #1 Intensive Care Unit

Kiev, , Ukraine

Kiev City Clinical Hospital No 5, Coronary Care Unit

Kiev, , Ukraine

N.D. Strazhesko Institute of Cardiology Intensive Care Unit

Kiev, , Ukraine

Lugansk First Clinical Multiprofile Hospital #1, Cardiology

Luhansk, , Ukraine

Lviv Reg St Clinical Treat-and-Diagn Cardio. Centre Dept of Myocardial Infarction

Lviv, , Ukraine

City Clinical Hospital #9 Dept of Arrhythmia

Odesa, , Ukraine

Countries

Bulgaria; Australia; Canada; Czechia; Denmark; Estonia; Finland; France; Germany; Latvia; Lithuania; Netherlands; Poland; Serbia; Slovakia; Sweden; Ukraine

References

Camm AJ, Capucci A, Hohnloser SH, Torp-Pedersen C, Van Gelder IC, Mangal B, Beatch G; AVRO Investigators. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation. J Am Coll Cardiol. 2011 Jan 18;57(3):313-21. doi: 10.1016/j.jacc.2010.07.046.

Reference Type: DERIVED

PMID: 21232669 (View on PubMed)

Other Identifiers

VERI-305-AMIO

Identifier Type: -

Identifier Source: org_study_id