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

NCT00668759 | Completed Phase 3

• 1 other identifier: VERI-305-AMIO
• Study Type: interventional
• Target: 254
• Locations: 15 countries
• Sites: 97

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.

Conditions

Atrial Fibrillation

Keywords

atrial fibrillation; atrial fib; AF

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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.

Study Arms (2)

1

EXPERIMENTAL

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.

Drug: Vernakalant Injection

2

ACTIVE COMPARATOR

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.

Drug: Amiodarone Injection:

Interventions

Vernakalant Injection 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).

Also known as: RSD1235, Kynapid

1

Amiodarone Injection: 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).

Also known as: Amiodarone, Cordarone

2

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Advanz Pharma: lead

Study Sites (100)

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Royal Hobart Hospital Cardiology Research

Hobart, Tasmania, 7000, Australia

Location

Launceston General Hospital Cardiac Research Unit

Launceston, Tasmania, Australia

Location

Royal Perth Hospital Emergency Research

Perth, Western Australia, 6000, Australia

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1Y 4E9, Canada

Location

Hopital de la Cite-de-la-Sante

Laval, Quebec, H7M 3L9, Canada

Location

Institut de Cardiologie de Montreal

Montreal, Quebec, H1T 1C8, Canada

Location

Centre Hopitalier de L'Universite de Montreal - Hotel Dieu

Montreal, Quebec, H2W 1T8, Canada

Location

McGill University Health Center The Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

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

Terrebonne, Quebec, J6V 2H2, Canada

Location

Mestrska nemocnice Caslav

Čáslav, 286 01, Czechia

Location

Nemocnice Kroměříž

Kroměříž, 767 55, Czechia

Location

Nemocnice Kutna Hora s.r.o. Interni Oddeleni

Kutná Hora, Czechia

Location

Nemocnice Decin Internal Medicine

Nove Město, 405 02, Czechia

Location

Fakultní nemocnice v Motole, KAR

Prague, 150 00, Czechia

Location

Ustredni vojenska nemocnice Koronarni jednotka

Prague, 162 00, Czechia

Location

VFN - III. Interni Klinika

Prague, Czechia

Location

Oblastni nemocnice Pribram Interni Oddeleni

Příbram, Czechia

Location

Nemocnice v Semilech Interní oddělení

Semily, Czechia

Location

Nemocnice Slaný Interní oddělení

Slaný, Czechia

Location

Nemocnice Tabor

Tábor, 390 03, Czechia

Location

Uherskohradistska nemocnice

Uherské Hradiste, 686 08, Czechia

Location

Gentofte Amtssygehus Kardiologisk afdeling

Hellerup, Denmark

Location

Herlev Amtssygehus, Kardiologisk

Herlev, 2730, Denmark

Location

Sygehus Vendsyssel Hjorring

Hjørring, Denmark

Location

Roskilde Amts Sygehus Køge

Køge, Denmark

Location

Regionshospitalet Silkeborg

Silkeborg, Denmark

Location

Viimsi Hospital, Heart Clinic

Haabneeme, 74001, Estonia

Location

Pärnu Hospital Department of Cardiology

Pärnu, Estonia

Location

East Tallinn Central Hospital-Clinic of Cardiology

Tallinn, Estonia

Location

Tartu University Hospital Heart Clinic

Tartu, Estonia

Location

Oulu University Hospital - Dept of Internal Medicine

Oulu, 90014, Finland

Location

Hopital Trousseau - Service de Cardiologie

Chambray-lès-Tours, France

Location

CHU de Nancy - Hopital Brabois - Service de Cardiologie

Nancy, France

Location

Hôpital Lariboisiere

Paris, France

Location

CHU de Strasbourg - Hopital Hautepierre - Service de Cardiologie

Strasbourg, France

Location

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

Berlin, 10117, Germany

Location

Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin

Berlin, Germany

Location

Herzzentrum Brandenburg in Bernau Innere Medizin

Bernau, 16321, Germany

Location

Universitätsklinikum Bonn, Med. Klinik und Poliklinik II

Bonn, 53105, Germany

Location

Klinikum der Universität Köln, Medizinische Klinik III

Cologne, 50924, Germany

Location

Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie

Frankfurt, Germany

Location

Universitatsklinikum Gottingen, Herzzentrum

Göttingen, 37075, Germany

Location

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

Halle, Germany

Location

Klinik Hamburg Bambek Kardiologie

Hamburg, 22291, Germany

Location

Medizinisches Versorgungszentrum Prof. Mathey, Prof. Schofer GmbH

Hamburg, 22527, Germany

Location

Medizinische Klinik, Klinikum Hannover Nordstadt

Hanover, Germany

Location

Ambulantes Herzzentrum Kassel Innere Medizin

Kassel, 34121, Germany

Location

Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen, 67063, Germany

Location

Carl-von Basedow-Klinikum Merseburg

Merseburg, 06217, Germany

Location

Klinikum Pirna GmbH, Innere Medizin II, Kardiologie

Pirna, Germany

Location

Krankenhaus Reinbek, St. Adolf-Stift

Reinbek, Germany

Location

Robert-Bosch-Krankenhaus, Abt. Kardiologie / Pulmologie

Stuttgart, 70376, Germany

Location

Latvian Center of Cardiology, P. Stradins Clinical University Hospital

Riga, LV1002, Latvia

Location

Kaunas Medical University Hospital - Department of Cardiology

Kaunas, Lithuania

Location

Klaipeda Seamen's Hospital

Klaipėda, Lithuania

Location

Vilnius University Hospital Santariskiu Clinic - Center of Cardiology and Angiology

Vilnius, Lithuania

Location

WCN - Department of Cardiology Rijnstate Ziekenhuls

Arnhem, 6-800 TA, Netherlands

Location

Catharina Ziekenhuis Eindhoven

Eindhoven, 5623EJ, Netherlands

Location

Groene Hart Zeikenhhaus

Gouda, 2800BB, Netherlands

Location

WCN - Bethesda ziekenhuis

Hoogeveen, 7909 AA, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, 6229 HX, Netherlands

Location

WCN - Canisius-Wilhelmina Ziekenhuis

Nijmegen, 6532 SZ, Netherlands

Location

WCN - St. Franciscus Gasthuis

Rotterdam, 3045 PM, Netherlands

Location

Oddzial Kardiologiczny Wielospecjalityczny Szpital Miejski im.

Bydgoszcz, Poland

Location

Szpital Miejski im. J. Brudzinskiego Oddzial Kardiologii

Gdynia, Poland

Location

Klinika Chorob Wewnetrznych z Oddzialem Farmakologii Klinicznej i Terapii Monitorowanej

Lodz, Poland

Location

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

Lublin, 20-089, Poland

Location

Okregowy Szpital Kolejowy w Lublinie Samodzielny

Lublin, Poland

Location

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

Tarnów, 33-100, Poland

Location

Oddział Kardiologiczno-Internistyczny Specjalistyczny Szpital Miejski im. Mikołaja Kopernika

Torun, 87-100, Poland

Location

Specjalistyczny Szpital Miejski im. Mikołaja Kopernika

Torun, 87-100, Poland

Location

III Klinika Chorob Wewnetrznych i Kardiologii

Warsaw, 00-382, Poland

Location

Wojskowy Instytut Medyczny, CSK MON

Warsaw, 00-909, Poland

Location

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

Warsaw, 02-507, Poland

Location

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

Wroclaw, Poland

Location

Clinical Center of Serbia, Institute of CV Diseases

Belgrade, 11000, Serbia

Location

"Dedinje" Cardiovascular Institute

Belgrade, 11040, Serbia

Location

Institute of Treatment and Reahabilitation 'Niska Banja'

Niška Banja, 18205, Serbia

Location

Clinical Center Zemun, Dept. of Cardiology

Zemun, 11080, Serbia

Location

Middle Slovak Institute of Cardiovascular Diseases (SUSCCH)

Banska Bysterica, 97401, Slovakia

Location

NsP Prievidza so sidlom v Bojniciah

Bojnice, 97201, Slovakia

Location

Slovensky ustav srdcovych a cevnych chorob

Bratislava, 83348, Slovakia

Location

ICU, Hospital Lipt. Mikulas

Liptovský Mikuláš, 03101, Slovakia

Location

FN - I. interna klinika

Nitra, 950 01, Slovakia

Location

Liva - Central Military Hospital

Ružomberok, 03401, Slovakia

Location

Interna klinika FN Trnava, Fakultna nemocnica Trnava

Trnava, 91701, Slovakia

Location

Internal Dep. Hospital Žilina

Žilina, 012 07, Slovakia

Location

Universitetssjukhuset MAS

Malmo, Sweden

Location

Universityetssjukhuset, Orebro

Örebro, Sweden

Location

Akademiska Sjukhuset, Uppsala

Uppsala, Sweden

Location

Donetsk Regional Clinical Hospital

Donetsk, Ukraine

Location

City Clinical Hospital #8

Kharkiv, Ukraine

Location

City Clinical Hospital #1 Intensive Care Unit

Kiev, Ukraine

Location

Kiev City Clinical Hospital No 5, Coronary Care Unit

Kiev, Ukraine

Location

N.D. Strazhesko Institute of Cardiology Intensive Care Unit

Kiev, Ukraine

Location

Lugansk First Clinical Multiprofile Hospital #1, Cardiology

Luhansk, Ukraine

Location

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

Lviv, Ukraine

Location

City Clinical Hospital #9 Dept of Arrhythmia

Odesa, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 21232669 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

vernakalant; Amiodarone

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Tomas Janota, MD

  VFN III. interní klinika

  PRINCIPAL INVESTIGATOR

• Christian Torp-Pedersen, MD

  Gentofte Amtssygehus - Kardiologisk afdeling

  PRINCIPAL INVESTIGATOR

• Rein Kolk, MD

  Tartu University Hospital Heart Clinic

  PRINCIPAL INVESTIGATOR

• Etienne Aliot, MD

  CHU de Nancy - Hopital Brabois, Service de Cardiologie

  PRINCIPAL INVESTIGATOR

• Stefan Hohnloser, MD

  Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie

  PRINCIPAL INVESTIGATOR

• Heikki Huikuri, MD

  Oulu University Hospital - Dept of Internal Medicine

  PRINCIPAL INVESTIGATOR

• Piotr Ponikowski, MD

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

  PRINCIPAL INVESTIGATOR

• Steen Juul-Moller, MD

  Universitetssjukhuset MAS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 25, 2008
• First Posted: April 29, 2008
• Study Start: April 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: November 1, 2009
• Last Updated: December 15, 2009

Record last verified: 2009-12

Locations

SE (4); CA (7); CZ (12); FI (1); ES (4); DE (17); UA (8); FR (4); LI (3); SL (8); DK (5); LA (1); AU (4); NL (7); PL (12)