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

Condition(s) targeted: Atrial Fibrillation

Intervention: Vernakalant Injection (Drug); Amiodarone Injection: (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Cardiome Pharma

Official(s) and/or principal investigator(s):
Tomas Janota, MD, Principal Investigator, Affiliation: VFN III. interní klinika
Christian Torp-Pedersen, MD, Principal Investigator, Affiliation: Gentofte Amtssygehus - Kardiologisk afdeling
Rein Kolk, MD, Principal Investigator, Affiliation: Tartu University Hospital Heart Clinic
Etienne Aliot, MD, Principal Investigator, Affiliation: CHU de Nancy - Hopital Brabois, Service de Cardiologie
Stefan Hohnloser, MD, Principal Investigator, Affiliation: Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie
Audrius Aidietis, MD, Principal Investigator, Affiliation: Vilnius University Hospital Santariskiu Clinic - Center of Cardiology and Angiology
Piotr Ponikowski, MD, Principal Investigator, Affiliation: Osrodek Chorob Serca, Klinika Kardiologii, IV Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej we Wroclawiu
Steen Juul-Moller, MD, Principal Investigator, Affiliation: Universitetssjukhuset MAS

Overall contact:
Heather Kato, MAppSc, Phone: 604-677-6905, Ext: 135, Email: hkato@cardiome.com

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.

Official title: A Phase III Prospective, Randomized, Double-Blind, Active-Controlled, Multi-Center, Superiority Study of Vernakalant Injection Versus Amiodarone in Subjects With Recent Onset Atrial Fibrillation

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Proportion of subjects with conversion of atrial fibrillation to sinus rhythm within 90 minutes after the start of infusion.

Secondary outcome:

Time to conversion within 90 minutes after the start of infusion.

Proportion of subjects with symptom relief at 90 minutes after the start of infusion.

EQ-5D quality of life assessment.

Monitoring of adverse events, vital signs, continuous telemetry monitoring, 12-lead Holter monitoring, 12-lead ECGs, and laboratory tests.

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.

Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Both.

Criteria:

Key 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.

Key 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.

Heather Kato, MAppSc, Phone: 604-677-6905, Ext: 135, Email: hkato@cardiome.com

Nemocnice Slaný Interní oddělení, Slaný, Czech Republic; Recruiting
Ondrej Cermak, MD, Phone: 420-312-575-338
Ondrej Cermak, MD, Principal Investigator

VFN - III. Interni Klinika, Praha, Czech Republic; Recruiting
Tomas Janota, MD, Phone: 420-224-962-934
Tomas Janota, MD, Principal Investigator

Nemocnice v Semilech Interní oddělení, Semily, Czech Republic; Recruiting
Pavel Sabl, MD, Phone: 420-481-661-333
Pavel Sabl, MD, Principal Investigator

Ustredni vojenska nemocnice Koronarni jednotka, Praha, Czech Republic; Recruiting
Pavel Sedlon, MD, Phone: 420-973-203-043
Pavel Sedlon, MD, Principal Investigator

Nemocnice Kroměříž, Kroměříž, Czech Republic; Recruiting
Lumir Francek, MD, Phone: 420-573-322-467
Lumir Francek, MD, Principal Investigator

Nemocnice Kutna Hora s.r.o. Interni Oddeleni, Kutna Hora, Czech Republic; Recruiting
Michal Oščipovský, MD, Phone: 420-327-503-316
Michal Oščipovský, MD, Principal Investigator

Oblastni nemocnice Pribram Interni Oddeleni, Pribram, Czech Republic; Recruiting
Martin Polak, MD, Phone: 420-318-641-262
Martin Polak, MD, Principal Investigator

Fakultní nemocnice v Motole, KAR, Praha, Czech Republic; Recruiting
Tomas Vymazal, MD, Phone: 420 224 435 252
Tomas Vymazal, MD, Principal Investigator

Gentofte Amtssygehus Kardiologisk afdeling, Hellerup, Denmark; Recruiting
Gitte von Jessen, Phone: 45 35 31 27 71, Email: gvj@heart.dk
Christian Torp-Pedersen, MD, Principal Investigator

Regionshospitalet Silkeborg, Silkeborg, Denmark; Recruiting
Malene Mortensen, Phone: 45 87 22 23 49, Email: projektM1@sc.aaa.dk
Lars Frost, MD, Principal Investigator

Roskilde Amts Sygehus Køge, Koge, Denmark; Recruiting
Lone Brinksby, Phone: 45 47 32 25 56, Email: Lone: lbrn@regionsjaelland.dk
Kim Klarlund, MD, Principal Investigator

Sygehus Vendsyssel Hjorring, Hjorring, Denmark; Recruiting
Jens Petersen, MD, Phone: 45 99 64 31 01
Jens Petersen, MD, Principal Investigator

Herlev Amtssygehus, Kardiologisk, Herlev, Denmark; Recruiting
Knud Skagen, MD, Phone: 45 44 88 44 88
Knud Skagen, MD, Principal Investigator

Tartu University Hospital Heart Clinic, Tartu, Estonia; Recruiting
Rein Kolk, MD, Phone: 372 7 318 450
Rein Kolk, MD, Principal Investigator

Pärnu Hospital Department of Cardiology, Parnu, Estonia; Recruiting
Veiko Vahula, MD, Phone: 372 44 73310
Veiko Vahula, MD, Principal Investigator

East Tallinn Central Hospital-Clinic of Cardiology, Tallinn, Estonia; Recruiting
Anne Kork, MD, Phone: 372 62 07056
Anne Kork, MD, Principal Investigator

CHU de Nancy - Hopital Brabois - Service de Cardiologie, Nancy, France; Recruiting
Etienne Aliot, MD, Phone: 33 3 83 15 32 96
Etienne Aliot, MD, Principal Investigator

CHU de Strasbourg - Hopital Hautepierre - Service de Cardiologie, Strasbourg, France; Recruiting
Gerald Jose Roul, MD, Phone: 33 3 88 12 72 06
Gerald J Roul, MD, Principal Investigator

Hôpital Lariboisiere, Paris, France; Recruiting
Antoine Leenhardt, MD, Phone: 33 1 49 95 82 23
Antoine Leenhardt, MD, Principal Investigator

Hopital Trousseau - Service de Cardiologie, Chambray-les-Tours, France; Recruiting
Dominique Babuty, MD, Phone: 33 0 247 47 46 50
Dominique Babuty, MD, Principal Investigator

Klinikum Pirna GmbH, Innere Medizin II, Kardiologie, Pirna, Germany; Recruiting
Christoph Axthelm, MD, Phone: 49 3501 7118 5041
Christoph Axthelm, MD, Principal Investigator

Klinikum der Universität Köln, Medizinische Klinik III, Koln, Germany; Recruiting
Frank Baer, MD, Phone: 49 221 4783 2401
Frank Baer, MD, Principal Investigator

Martin-Luther Universitat Halle, Med. Klinik und Poliklinik III- Fachrichtung Kardiologie, Halle, Germany; Recruiting
Michael Buerke, MD, Phone: 49 221 4783 2401
Michael Buerke, MD, Principal Investigator

Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin, Berlin, Germany; Recruiting
Wilhelm Haverkamp, MD, Phone: 49 30 450 653366
Wilhelm Haverkamp, MD, Principal Investigator

Medizinische Klinik, Klinikum Hannover Nordstadt, Hannover, Germany; Recruiting
Johannes Hensen, MD, Phone: 49 511 9701291
Johannes Hensen, MD, Principal Investigator

Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie, Frankfurt, Germany; Recruiting
Stefan Hohnloser, MD, Phone: 49 69 6301 7404
Stefan Hohnloser, MD, Principal Investigator

Krankenhaus Reinbek, St. Adolf-Stift, Reinbek, Germany; Recruiting
Herbert Naegele, MD, Phone: 49 40 72805158
Herbert Naegele, MD, Principal Investigator

Universitätsklinikum Bonn, Med. Klinik und Poliklinik II, Bonn, Germany; Recruiting
Lars Lickfett, MD, Phone: 49 228 287 16861
Lars Lickfett, MD, Principal Investigator

Charite Campus Mitte, Med. Klinik und Poliklinik mit Schwerpunkt Kardiologie und Angiologie, Berlin, Germany; Recruiting
Verena Stangl, MD, Phone: 49 30 450 513 142
Verena Stangl, MD, Principal Investigator

Universitatsklinikum Gottingen, Herzzentrum, Gottingen 37075, Germany; Recruiting
Rolf Wachter, MD, Phone: 49 551 398920, Email: rwachter@med.uni-goettingen.de
Rolf Wachter, MD, Principal Investigator

Vilnius University Hospital Santariskiu Clinic - Center of Cardiology and Angiology, Vilnius, Lithuania; Recruiting
Audrius Aidietis, MD, Phone: 370 5 2365216
Audrius Aidietis, MD, Principal Investigator

Klaipeda Seamen's Hospital, Klaipeda, Lithuania; Recruiting
Dalia Jarasuniene, MD, Phone: 370 685 26606
Dalia Jarasuniene, MD, Principal Investigator

Kaunas Medical University Hospital - Department of Cardiology, Kaunas, Lithuania; Recruiting
Gintare Sakalyte, MD, Phone: 370 69 806044
Gintare Sakalyte, MD, Principal Investigator

Klinika Chorob Wewnetrznych z Oddzialem Farmakologii Klinicznej i Terapii Monitorowanej, Lodz, Poland; Recruiting
Julita Chojnowska-Jezierska, MD, Phone: 48 42 6511059
Julita Chojnowska-Jezierska, MD, Principal Investigator

Oddzial Kardiologii Inwazyjnej Szpital Specjalistyczny im. E.Szczeklika w Tarnowie, Tarnow, Poland; Recruiting
Boguslaw Derlaga, MD, Phone: 48 14 6310519
Boguslaw Derlaga, MD, Principal Investigator

Oddzial Kardiologiczny Wielospecjalityczny Szpital Miejski im., Bydgoszcz, Poland; Recruiting
Andrzej Hoffmann, MD, Phone: 48 52 3709300
Andrzej Hoffmann, MD, Principal Investigator

Szpital Miejski im. J. Brudzinskiego Oddzial Kardiologii, Gdynia, Poland; Recruiting
Pawel Miekus, MD, Phone: 48 58 6665580
Pawel Miekus, MD, Principal Investigator

Osrodek Chorob Serca, Klinika Kardiologii, 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny, Wroclaw, Poland; Recruiting
Piotr Ponikowski, MD, Phone: 48 71 7660250
Piotr Ponikowski, MD, Principal Investigator

Okregowy Szpital Kolejowy w Lublinie Samodzielny, Lublin, Poland; Recruiting
Ryszard Trojnar, MD, Phone: 48 81 7604234
Ryszard Trojnar, MD, Principal Investigator

Wojskowy Instytut Medyczny, CSK MON, Warszawa 00-909, Poland; Not yet recruiting
Leszek Kubik, MD, Phone: 48 22 6816585, Email: lkubik@wim.mil.pl
Leszek Kubik, MD, Principal Investigator

III Klinika Chorob Wewnetrznych i Kardiologii, Warszawa 00-382, Poland; Not yet recruiting
Krzysztof Makowiecki, MD, Phone: 48 22 6252231, Email: krzysztofmakowiecki@wp.pl
Krzysztof Makowiecki, MD, Principal Investigator

Universitetssjukhuset MAS, Malmo, Sweden; Recruiting
Hjördis Jernhed, Phone: 46 40 332235
Steen Juul-Moller, MD, Principal Investigator

Akademiska Sjukhuset, Uppsala, Uppsala, Sweden; Recruiting
Yvonne Björkman, Phone: 46 18 6112738
Per Blomstrom, MD, Principal Investigator

Universityetssjukhuset, Orebro, Orebro, Sweden; Recruiting
Lena Swedberg, Phone: 46 19 602 1000
Espen Fensgrud, MD, Principal Investigator

Kiev City Clinical Hospital No 5, Coronary Care Unit, Kiev, Ukraine; Not yet recruiting
Valerii Batushkin, MD, Phone: 38 067 502 0076
Valerii Batushkin, MD, Principal Investigator

Lviv Reg St Clinical Treat-and-Diagn Cardio. Centre Dept of Myocardial Infarction, Lviv, Ukraine; Not yet recruiting
Andriy Faynyk, MD, Phone: 38 050 532 9828
Andriy Faynyk, MD, Principal Investigator

City Clinical Hospital #1 Intensive Care Unit, Kiev, Ukraine; Not yet recruiting
Oleksandr Karpenko, MD, Phone: 38 050 311 43 83
Oleksandr Karpenko, MD, Principal Investigator

City Clinical Hospital #9 Dept of Arrhythmia, Odessa, Ukraine; Not yet recruiting
Yuriy Karpenko, MD, Phone: 38 050 333 3727
Yuriy Karpenko, MD, Principal Investigator

Donetsk Regional Clinical Hospital, Donetsk, Ukraine; Not yet recruiting
Sergiy Nalotov, MD, Phone: 38 062 295 8444
Sergiy Nalotov, MD, Principal Investigator

N.D. Strazhesko Institute of Cardiology Intensive Care Unit, Kiev, Ukraine; Not yet recruiting
Alexander Parkhomenko, MD, Phone: 38 050 353 1633
Alexander Parkhomenko, MD, Principal Investigator

Lugansk First Clinical Multiprofile Hospital #1, Cardiology, Lugansk, Ukraine; Not yet recruiting
Pavel Potapenko, MD, Phone: 38 064 233 1927
Pavel Potapenko, MD, Principal Investigator

City Clinical Hospital #8, Kharkiv, Ukraine; Not yet recruiting
Vera Tseluyko, MD, Phone: 38 057 710 9881
Vera Tseluyko, MD, Principal Investigator

The Ottawa Hospital, Ottawa, Ontario K1Y 4E9, Canada; Not yet recruiting
Cathy Clement, RN, Phone: 613 798 5555, Ext: 16615, Email: cclement@ohri.ca
Ian Stiell, MD, Principal Investigator

Institut de Cardiologie de Montreal, Montreal, Quebec H1T 1C8, Canada; Not yet recruiting
Constance Bossy, RN, Phone: 514 376 3330, Ext: 2884, Email: Constance.Bossy@icm-mhi.org
Denis Roy, MD, Principal Investigator

Centre Hopitalier de L'Universite de Montreal - Hotel Dieu, Montreal, Quebec H2W 1T8, Canada; Not yet recruiting
Carole Lemay, RN, Phone: 514 890 8000, Ext: 14803, Email: recherche.cardio.hd.chum@ssss.gouv.gc.ca
Paolo Costi, MD, Principal Investigator

Centre de santé et de services sociaux du Sud de Lanaudière - Hôpital Pierre-Le Gardeur, Terrebonne, Quebec J6V 2H2, Canada; Not yet recruiting
Margaux David, RN, Phone: 450 654 7525, Ext: 11104, Email: chlg.rech.cardio@ssss.gouv.qc.ca
Denis-Carl Phaneuf, MD, Principal Investigator

Starting date: April 2008
Ending date: February 2009
Last updated: September 29, 2008