A Phase III Superiority Study of Vernakalant vs Amiodarone in Subjects With Recent Onset Atrial Fibrillation
- Registration Number
- NCT00668759
- Lead Sponsor
- Advanz Pharma
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 254
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Vernakalant Injection 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.
- Primary Outcome Measures
Name Time Method Proportion of subjects with conversion of atrial fibrillation to sinus rhythm within 90 minutes after the start of infusion. Conversion of AF to SR for a minimum duration of one minute within 90 minutes after start of infusion.
- Secondary Outcome Measures
Name Time Method Time to conversion within 90 minutes after the start of infusion. Time to conversion of AF to SR within 90 minutes after start of infusion. Proportion of subjects with symptom relief at 90 minutes after the start of infusion. Relief of AF symptoms 90 minutes after start of infusion. EQ-5D quality of life assessment. Assessment of quality of life 2 hours after start of infusion. Monitoring of adverse events, vital signs, continuous telemetry monitoring, 12-lead Holter monitoring, 12-lead ECGs, and laboratory tests. Specified safety assessments completed at specified time points throughout the study from Screening to Discharge, at the Day 7 visit, and at the Day 30 follow-up call.
Trial Locations
- Locations (100)
Royal Perth Hospital Emergency Research
🇦🇺Perth, Western Australia, Australia
Gentofte Amtssygehus Kardiologisk afdeling
🇩🇰Hellerup, Denmark
Herlev Amtssygehus, Kardiologisk
🇩🇰Herlev, Denmark
Sygehus Vendsyssel Hjorring
🇩🇰Hjorring, Denmark
Roskilde Amts Sygehus Køge
🇩🇰Koge, Denmark
Regionshospitalet Silkeborg
🇩🇰Silkeborg, Denmark
Nemocnice v Semilech Interní oddělení
🇨🇿Semily, Czech Republic
Uherskohradistska nemocnice
🇨🇿Uherské Hradiste, Czech Republic
VFN - III. Interni Klinika
🇨🇿Praha, Czech Republic
Viimsi Hospital, Heart Clinic
🇪🇪Haabneeme, Estonia
Ustredni vojenska nemocnice Koronarni jednotka
🇨🇿Praha, Czech Republic
Oblastni nemocnice Pribram Interni Oddeleni
🇨🇿Pribram, Czech Republic
Oulu University Hospital - Dept of Internal Medicine
🇫🇮Oulu, Finland
Hôpital Lariboisiere
🇫🇷Paris, France
Universitätsklinikum Bonn, Med. Klinik und Poliklinik II
🇩🇪Bonn, Germany
Medizinische Klinik, Klinikum Hannover Nordstadt
🇩🇪Hannover, Germany
Charite Campus Mitte, Med. Klinik und Poliklinik mit Schwerpunkt Kardiologie und Angiologie
🇩🇪Berlin, Germany
CHU de Strasbourg - Hopital Hautepierre - Service de Cardiologie
🇫🇷Strasbourg, France
Universitatsklinikum Gottingen, Herzzentrum
🇩🇪Gottingen, Germany
Universitetssjukhuset MAS
🇸🇪Malmo, Sweden
Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Herzzentrum Brandenburg in Bernau Innere Medizin
🇩🇪Bernau, Germany
Klinik Hamburg Bambek Kardiologie
🇩🇪Hamburg, Germany
Ambulantes Herzzentrum Kassel Innere Medizin
🇩🇪Kassel, Germany
Klaipeda Seamen's Hospital
🇱🇹Klaipeda, Lithuania
WCN - Bethesda ziekenhuis
🇳🇱Hoogeveen, Netherlands
Specjalistyczny Szpital Miejski im. Mikołaja Kopernika
🇵🇱Toruń, Poland
Launceston General Hospital Cardiac Research Unit
🇦🇺Launceston, Tasmania, Australia
Royal Hobart Hospital Cardiology Research
🇦🇺Hobart, Tasmania, Australia
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
🇨🇿Caslav, Czech Republic
Nemocnice Kroměříž
🇨🇿Kroměříž, Czech Republic
CHU de Nancy - Hopital Brabois - Service de Cardiologie
🇫🇷Nancy, France
Nemocnice Kutna Hora s.r.o. Interni Oddeleni
🇨🇿Kutna Hora, Czech Republic
Nemocnice Decin Internal Medicine
🇨🇿Nove Město, Czech Republic
Fakultní nemocnice v Motole, KAR
🇨🇿Praha, Czech Republic
Nemocnice Tabor
🇨🇿Tabor, Czech Republic
Tartu University Hospital Heart Clinic
🇪🇪Tartu, Estonia
Nemocnice Slaný Interní oddělení
🇨🇿Slaný, Czech Republic
Hopital Trousseau - Service de Cardiologie
🇫🇷Chambray-les-Tours, France
Latvian Center of Cardiology, P. Stradins Clinical University Hospital
🇱🇻Riga, Latvia
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Catharina Ziekenhuis Eindhoven
🇳🇱Eindhoven, Netherlands
WCN - St. Franciscus Gasthuis
🇳🇱Rotterdam, Netherlands
WCN - Canisius-Wilhelmina Ziekenhuis
🇳🇱Nijmegen, Netherlands
Oddzial Kardiologiczny Wielospecjalityczny Szpital Miejski im.
🇵🇱Bydgoszcz, Poland
Universityetssjukhuset, Orebro
🇸🇪Orebro, Sweden
Szpital Miejski im. J. Brudzinskiego Oddzial Kardiologii
🇵🇱Gdynia, Poland
Oddział Internistyczno-Kardiologiczny Samodzielny Publiczny Szpital Wojewódzki im. Jana Bożego w Lublinie
🇵🇱Lublin, Poland
Oddzial Kardiologii Inwazyjnej Szpital Specjalistyczny im. E.Szczeklika w Tarnowie
🇵🇱Tarnow, Poland
Oddział Kardiologiczno-Internistyczny Specjalistyczny Szpital Miejski im. Mikołaja Kopernika
🇵🇱Toruń, Poland
III Klinika Chorob Wewnetrznych i Kardiologii
🇵🇱Warszawa, Poland
Wojskowy Instytut Medyczny, CSK MON
🇵🇱Warszawa, Poland
Osrodek Chorob Serca, Klinika Kardiologii, 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny
🇵🇱Wroclaw, Poland
Klinika Kardiologii Zachowawczej Centralny Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji w Warszawie
🇵🇱Warszawa, Poland
Institute of Treatment and Reahabilitation 'Niska Banja'
🇷🇸Niska Banja, Serbia
Clinical Center Zemun, Dept. of Cardiology
🇷🇸Zemun, Serbia
Interna klinika FN Trnava, Fakultna nemocnica Trnava
🇸🇰Trnava, Slovakia
Middle Slovak Institute of Cardiovascular Diseases (SUSCCH)
🇸🇰Banska Bysterica, Slovakia
Slovensky ustav srdcovych a cevnych chorob
🇸🇰Bratislava, Slovakia
ICU, Hospital Lipt. Mikulas
🇸🇰Liptovsky Mikulas, Slovakia
NsP Prievidza so sidlom v Bojniciah
🇸🇰Bojnice, Slovakia
City Clinical Hospital #1 Intensive Care Unit
🇺🇦Kiev, Ukraine
Akademiska Sjukhuset, Uppsala
🇸🇪Uppsala, Sweden
Kiev City Clinical Hospital No 5, Coronary Care Unit
🇺🇦Kiev, Ukraine
City Clinical Hospital #8
🇺🇦Kharkiv, Ukraine
Lugansk First Clinical Multiprofile Hospital #1, Cardiology
🇺🇦Lugansk, Ukraine
N.D. Strazhesko Institute of Cardiology Intensive Care Unit
🇺🇦Kiev, Ukraine
Lviv Reg St Clinical Treat-and-Diagn Cardio. Centre Dept of Myocardial Infarction
🇺🇦Lviv, Ukraine
City Clinical Hospital #9 Dept of Arrhythmia
🇺🇦Odessa, Ukraine
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Pärnu Hospital Department of Cardiology
🇪🇪Parnu, Estonia
Carl-von Basedow-Klinikum Merseburg
🇩🇪Merseburg, Germany
Kaunas Medical University Hospital - Department of Cardiology
🇱🇹Kaunas, Lithuania
Medizinisches Versorgungszentrum Prof. Mathey, Prof. Schofer GmbH
🇩🇪Hamburg, Germany
East Tallinn Central Hospital-Clinic of Cardiology
🇪🇪Tallinn, Estonia
WCN - Department of Cardiology Rijnstate Ziekenhuls
🇳🇱Arnhem, Netherlands
Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin
🇩🇪Berlin, Germany
Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie
🇩🇪Frankfurt, Germany
Klinikum der Stadt Ludwigshafen am Rhein gGmbH
🇩🇪Ludwigshafen, Germany
Krankenhaus Reinbek, St. Adolf-Stift
🇩🇪Reinbek, Germany
Groene Hart Zeikenhhaus
🇳🇱Gouda, Netherlands
FN - I. interna klinika
🇸🇰Nitra, Slovakia
Liva - Central Military Hospital
🇸🇰Ruzomberok, Slovakia
Donetsk Regional Clinical Hospital
🇺🇦Donetsk, Ukraine
Martin-Luther Universitat Halle, Med. Klinik und Poliklinik III- Fachrichtung Kardiologie
🇩🇪Halle, Germany
Vilnius University Hospital Santariskiu Clinic - Center of Cardiology and Angiology
🇱🇹Vilnius, Lithuania
Klinika Chorob Wewnetrznych z Oddzialem Farmakologii Klinicznej i Terapii Monitorowanej
🇵🇱Lodz, Poland
Okregowy Szpital Kolejowy w Lublinie Samodzielny
🇵🇱Lublin, Poland
Clinical Center of Serbia, Institute of CV Diseases
🇷🇸Belgrade, Serbia
"Dedinje" Cardiovascular Institute
🇷🇸Belgrade, Serbia
Klinikum der Universität Köln, Medizinische Klinik III
🇩🇪Köln, Germany
Klinikum Pirna GmbH, Innere Medizin II, Kardiologie
🇩🇪Pirna, Germany
Robert-Bosch-Krankenhaus, Abt. Kardiologie / Pulmologie
🇩🇪Stuttgart, Germany
Internal Dep. Hospital Žilina
🇸🇰Žilina, Slovakia