Clinical trial NCT00668759: A Phase III Superiority Study of Vernakalant vs Amiodarone in Subjects With Recent Onset Atrial Fibrillation
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Keywords: atrial fibrillation
atrial fib
AF
Lead sponsor: Advanz Pharma
Sponsor class: INDUSTRY
First posted: 2008-04-29
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Proportion of subjects with conversion of atrial fibrillation to sinus rhythm within 90 minutes after the start of infusion.
timeFrame: Conversion of AF to SR for a minimum duration of one minute within 90 minutes after start of infusion.
Secondary outcomes:
measure: Time to conversion within 90 minutes after the start of infusion.
timeFrame: Time to conversion of AF to SR within 90 minutes after start of infusion.
measure: Proportion of subjects with symptom relief at 90 minutes after the start of infusion.
timeFrame: Relief of AF symptoms 90 minutes after start of infusion.
measure: EQ-5D quality of life assessment.
timeFrame: Assessment of quality of life 2 hours after start of infusion.
measure: Monitoring of adverse events, vital signs, continuous telemetry monitoring, 12-lead Holter monitoring, 12-lead ECGs, and laboratory tests.
timeFrame: 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.
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital Cardiology Research
state: Tasmania
city: Launceston
country: Australia
facility: Launceston General Hospital Cardiac Research Unit
state: Tasmania
city: Perth
country: Australia
facility: Royal Perth Hospital Emergency Research
state: Western Australia
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Laval
country: Canada
facility: Hopital de la Cite-de-la-Sante
state: Quebec
city: Montreal
country: Canada
facility: Institut de Cardiologie de Montreal
state: Quebec
city: Montreal
country: Canada
facility: Centre Hopitalier de L'Universite de Montreal - Hotel Dieu
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center The Montreal General Hospital
state: Quebec
city: Terrebonne
country: Canada
facility: Centre de santé et de services sociaux du Sud de Lanaudière - Hôpital Pierre-Le Gardeur
state: Quebec
city: Caslav
country: Czech Republic
facility: Mestrska nemocnice Caslav
city: Kroměříž
country: Czech Republic
facility: Nemocnice Kroměříž
city: Kutna Hora
country: Czech Republic
facility: Nemocnice Kutna Hora s.r.o. Interni Oddeleni
city: Nove Město
country: Czech Republic
facility: Nemocnice Decin Internal Medicine
city: Praha
country: Czech Republic
facility: Fakultní nemocnice v Motole, KAR
city: Praha
country: Czech Republic
facility: Ustredni vojenska nemocnice Koronarni jednotka
city: Praha
country: Czech Republic
facility: VFN - III. Interni Klinika
city: Pribram
country: Czech Republic
facility: Oblastni nemocnice Pribram Interni Oddeleni
city: Semily
country: Czech Republic
facility: Nemocnice v Semilech Interní oddělení
city: Slaný
country: Czech Republic
facility: Nemocnice Slaný Interní oddělení
city: Tabor
country: Czech Republic
facility: Nemocnice Tabor
city: Uherské Hradiste
country: Czech Republic
facility: Uherskohradistska nemocnice
city: Hellerup
country: Denmark
facility: Gentofte Amtssygehus Kardiologisk afdeling
city: Herlev
country: Denmark
facility: Herlev Amtssygehus, Kardiologisk
city: Hjorring
country: Denmark
facility: Sygehus Vendsyssel Hjorring
city: Koge
country: Denmark
facility: Roskilde Amts Sygehus Køge
city: Silkeborg
country: Denmark
facility: Regionshospitalet Silkeborg
city: Haabneeme
country: Estonia
facility: Viimsi Hospital, Heart Clinic
city: Parnu
country: Estonia
facility: Pärnu Hospital Department of Cardiology
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital-Clinic of Cardiology
city: Tartu
country: Estonia
facility: Tartu University Hospital Heart Clinic
city: Oulu
country: Finland
facility: Oulu University Hospital - Dept of Internal Medicine
city: Chambray-les-Tours
country: France
facility: Hopital Trousseau - Service de Cardiologie
city: Nancy
country: France
facility: CHU de Nancy - Hopital Brabois - Service de Cardiologie
city: Paris
country: France
facility: Hôpital Lariboisiere
city: Strasbourg
country: France
facility: CHU de Strasbourg - Hopital Hautepierre - Service de Cardiologie
city: Berlin
country: Germany
facility: Charite Campus Mitte, Med. Klinik und Poliklinik mit Schwerpunkt Kardiologie und Angiologie
city: Berlin
country: Germany
facility: Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin
city: Bernau
country: Germany
facility: Herzzentrum Brandenburg in Bernau Innere Medizin
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Med. Klinik und Poliklinik II
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie
city: Gottingen
country: Germany
facility: Universitatsklinikum Gottingen, Herzzentrum
city: Halle
country: Germany
facility: Martin-Luther Universitat Halle, Med. Klinik und Poliklinik III- Fachrichtung Kardiologie
city: Hamburg
country: Germany
facility: Klinik Hamburg Bambek Kardiologie
city: Hamburg
country: Germany
facility: Medizinisches Versorgungszentrum Prof. Mathey, Prof. Schofer GmbH
city: Hannover
country: Germany
facility: Medizinische Klinik, Klinikum Hannover Nordstadt
city: Kassel
country: Germany
facility: Ambulantes Herzzentrum Kassel Innere Medizin
city: Köln
country: Germany
facility: Klinikum der Universität Köln, Medizinische Klinik III
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen am Rhein gGmbH
city: Merseburg
country: Germany
facility: Carl-von Basedow-Klinikum Merseburg
city: Pirna
country: Germany
facility: Klinikum Pirna GmbH, Innere Medizin II, Kardiologie
city: Reinbek
country: Germany
facility: Krankenhaus Reinbek, St. Adolf-Stift
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus, Abt. Kardiologie / Pulmologie
city: Riga
country: Latvia
facility: Latvian Center of Cardiology, P. Stradins Clinical University Hospital
city: Kaunas
country: Lithuania
facility: Kaunas Medical University Hospital - Department of Cardiology
city: Klaipeda
country: Lithuania
facility: Klaipeda Seamen's Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Clinic - Center of Cardiology and Angiology
city: Arnhem
country: Netherlands
facility: WCN - Department of Cardiology Rijnstate Ziekenhuls
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis Eindhoven
city: Gouda
country: Netherlands
facility: Groene Hart Zeikenhhaus
city: Hoogeveen
country: Netherlands
facility: WCN - Bethesda ziekenhuis
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: WCN - Canisius-Wilhelmina Ziekenhuis
city: Rotterdam
country: Netherlands
facility: WCN - St. Franciscus Gasthuis
city: Bydgoszcz
country: Poland
facility: Oddzial Kardiologiczny Wielospecjalityczny Szpital Miejski im.
city: Gdynia
country: Poland
facility: Szpital Miejski im. J. Brudzinskiego Oddzial Kardiologii
city: Lodz
country: Poland
facility: Klinika Chorob Wewnetrznych z Oddzialem Farmakologii Klinicznej i Terapii Monitorowanej
city: Lublin
country: Poland
facility: Oddział Internistyczno-Kardiologiczny Samodzielny Publiczny Szpital Wojewódzki im. Jana Bożego w Lublinie
city: Lublin
country: Poland
facility: Okregowy Szpital Kolejowy w Lublinie Samodzielny
city: Tarnow
country: Poland
facility: Oddzial Kardiologii Inwazyjnej Szpital Specjalistyczny im. E.Szczeklika w Tarnowie
city: Toruń
country: Poland
facility: Oddział Kardiologiczno-Internistyczny Specjalistyczny Szpital Miejski im. Mikołaja Kopernika
city: Toruń
country: Poland
facility: Specjalistyczny Szpital Miejski im. Mikołaja Kopernika
city: Warszawa
country: Poland
facility: III Klinika Chorob Wewnetrznych i Kardiologii
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny, CSK MON
city: Warszawa
country: Poland
facility: Klinika Kardiologii Zachowawczej Centralny Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji w Warszawie
city: Wroclaw
country: Poland
facility: Osrodek Chorob Serca, Klinika Kardiologii, 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia, Institute of CV Diseases
city: Belgrade
country: Serbia
facility: "Dedinje" Cardiovascular Institute
city: Niska Banja
country: Serbia
facility: Institute of Treatment and Reahabilitation 'Niska Banja'
city: Zemun
country: Serbia
facility: Clinical Center Zemun, Dept. of Cardiology
city: Banska Bysterica
country: Slovakia
facility: Middle Slovak Institute of Cardiovascular Diseases (SUSCCH)
city: Bojnice
country: Slovakia
facility: NsP Prievidza so sidlom v Bojniciah
city: Bratislava
country: Slovakia
facility: Slovensky ustav srdcovych a cevnych chorob
city: Liptovsky Mikulas
country: Slovakia
facility: ICU, Hospital Lipt. Mikulas
city: Nitra
country: Slovakia
facility: FN - I. interna klinika
city: Ruzomberok
country: Slovakia
facility: Liva - Central Military Hospital
city: Trnava
country: Slovakia
facility: Interna klinika FN Trnava, Fakultna nemocnica Trnava
city: Žilina
country: Slovakia
facility: Internal Dep. Hospital Žilina
city: Malmo
country: Sweden
facility: Universitetssjukhuset MAS
city: Orebro
country: Sweden
facility: Universityetssjukhuset, Orebro
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset, Uppsala
city: Donetsk
country: Ukraine
facility: Donetsk Regional Clinical Hospital
city: Kharkiv
country: Ukraine
facility: City Clinical Hospital #8
city: Kiev
country: Ukraine
facility: City Clinical Hospital #1 Intensive Care Unit
city: Kiev
country: Ukraine
facility: Kiev City Clinical Hospital No 5, Coronary Care Unit
city: Kiev
country: Ukraine
facility: N.D. Strazhesko Institute of Cardiology Intensive Care Unit
city: Lugansk
country: Ukraine
facility: Lugansk First Clinical Multiprofile Hospital #1, Cardiology
city: Lviv
country: Ukraine
facility: Lviv Reg St Clinical Treat-and-Diagn Cardio. Centre Dept of Myocardial Infarction
city: Odessa
country: Ukraine
facility: City Clinical Hospital #9 Dept of Arrhythmia
Study officials:
affiliation: VFN III. interní klinika
name: Tomas Janota, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gentofte Amtssygehus - Kardiologisk afdeling
name: Christian Torp-Pedersen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tartu University Hospital Heart Clinic
name: Rein Kolk, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Nancy - Hopital Brabois, Service de Cardiologie
name: Etienne Aliot, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie
name: Stefan Hohnloser, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oulu University Hospital - Dept of Internal Medicine
name: Heikki Huikuri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Osrodek Chorob Serca, Klinika Kardiologii, IV Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej we Wroclawiu
name: Piotr Ponikowski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitetssjukhuset MAS
name: Steen Juul-Moller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.