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

This study has been completed.
Sponsor:
Information provided by:
Cardiome Pharma
ClinicalTrials.gov Identifier:
NCT00668759
First received: April 25, 2008
Last updated: December 12, 2009
Last verified: December 2009
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Drug: Vernakalant Injection
Drug: Amiodarone Injection:
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Cardiome Pharma:

Primary Outcome Measures:
  • Proportion of subjects with conversion of atrial fibrillation to sinus rhythm within 90 minutes after the start of infusion. [ Time Frame: Conversion of AF to SR for a minimum duration of one minute within 90 minutes after start of infusion. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to conversion within 90 minutes after the start of infusion. [ Time Frame: Time to conversion of AF to SR within 90 minutes after start of infusion. ] [ Designated as safety issue: No ]
  • Proportion of subjects with symptom relief at 90 minutes after the start of infusion. [ Time Frame: Relief of AF symptoms 90 minutes after start of infusion. ] [ Designated as safety issue: No ]
  • EQ-5D quality of life assessment. [ Time Frame: Assessment of quality of life 2 hours after start of infusion. ] [ Designated as safety issue: No ]
  • Monitoring of adverse events, vital signs, continuous telemetry monitoring, 12-lead Holter monitoring, 12-lead ECGs, and laboratory tests. [ Time Frame: 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. ] [ Designated as safety issue: Yes ]

Enrollment: 254
Study Start Date: April 2008
Study Completion Date: November 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: 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).
Other Names:
  • RSD1235
  • Kynapid
Active Comparator: 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.

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).
Other Names:
  • Amiodarone
  • Cordarone

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

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00668759

  Hide Study Locations
Locations
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Tasmania
Royal Hobart Hospital Cardiology Research
Hobart, Tasmania, Australia, 7000
Launceston General Hospital Cardiac Research Unit
Launceston, Tasmania, Australia
Australia, Western Australia
Royal Perth Hospital Emergency Research
Perth, Western Australia, Australia, 6000
Canada, Ontario
Kingston General Hospital
Kingston, Ontario, Canada, K7L 2V7
The Ottawa Hospital
Ottawa, Ontario, Canada, K1Y 4E9
Canada, Quebec
Hopital de la Cite-de-la-Sante
Laval, Quebec, Canada, H7M 3L9
McGill University Health Center The Montreal General Hospital
Montreal, Quebec, Canada, H3G 1A4
Centre Hopitalier de L'Universite de Montreal - Hotel Dieu
Montreal, Quebec, Canada, H2W 1T8
Institut de Cardiologie de Montreal
Montreal, Quebec, Canada, H1T 1C8
Centre de santé et de services sociaux du Sud de Lanaudière - Hôpital Pierre-Le Gardeur
Terrebonne, Quebec, Canada, J6V 2H2
Czech Republic
Mestrska nemocnice Caslav
Caslav, Czech Republic, 286 01
Nemocnice Kroměříž
Kroměříž, Czech Republic, 767 55
Nemocnice Kutna Hora s.r.o. Interni Oddeleni
Kutna Hora, Czech Republic
Nemocnice Decin Internal Medicine
Nove Město, Czech Republic, 405 02
VFN - III. Interni Klinika
Praha, Czech Republic
Ustredni vojenska nemocnice Koronarni jednotka
Praha, Czech Republic, 162 00
Fakultní nemocnice v Motole, KAR
Praha, Czech Republic, 150 00
Oblastni nemocnice Pribram Interni Oddeleni
Pribram, Czech Republic
Nemocnice v Semilech Interní oddělení
Semily, Czech Republic
Nemocnice Slaný Interní oddělení
Slaný, Czech Republic
Nemocnice Tabor
Tabor, Czech Republic, 390 03
Uherskohradistska nemocnice
Uherské Hradiste, Czech Republic, 686 08
Denmark
Gentofte Amtssygehus Kardiologisk afdeling
Hellerup, Denmark
Herlev Amtssygehus, Kardiologisk
Herlev, Denmark, 2730
Sygehus Vendsyssel Hjorring
Hjorring, Denmark
Roskilde Amts Sygehus Køge
Koge, Denmark
Regionshospitalet Silkeborg
Silkeborg, Denmark
Estonia
Viimsi Hospital, Heart Clinic
Haabneeme, Estonia, 74001
Pärnu Hospital Department of Cardiology
Parnu, Estonia
East Tallinn Central Hospital-Clinic of Cardiology
Tallinn, Estonia
Tartu University Hospital Heart Clinic
Tartu, Estonia
Finland
Oulu University Hospital - Dept of Internal Medicine
Oulu, Finland, 90014
France
Hopital Trousseau - Service de Cardiologie
Chambray-les-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
Germany
Charite Campus Mitte, Med. Klinik und Poliklinik mit Schwerpunkt Kardiologie und Angiologie
Berlin, Germany, 10117
Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin
Berlin, Germany
Herzzentrum Brandenburg in Bernau Innere Medizin
Bernau, Germany, 16321
Universitätsklinikum Bonn, Med. Klinik und Poliklinik II
Bonn, Germany, 53105
Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie
Frankfurt, Germany
Universitatsklinikum Gottingen, Herzzentrum
Gottingen, Germany, 37075
Martin-Luther Universitat Halle, Med. Klinik und Poliklinik III- Fachrichtung Kardiologie
Halle, Germany
Klinik Hamburg Bambek Kardiologie
Hamburg, Germany, 22291
Medizinisches Versorgungszentrum Prof. Mathey, Prof. Schofer GmbH
Hamburg, Germany, 22527
Medizinische Klinik, Klinikum Hannover Nordstadt
Hannover, Germany
Ambulantes Herzzentrum Kassel Innere Medizin
Kassel, Germany, 34121
Klinikum der Universität Köln, Medizinische Klinik III
Köln, Germany, 50924
Klinikum der Stadt Ludwigshafen am Rhein gGmbH
Ludwigshafen, Germany, 67063
Carl-von Basedow-Klinikum Merseburg
Merseburg, Germany, 06217
Klinikum Pirna GmbH, Innere Medizin II, Kardiologie
Pirna, Germany
Krankenhaus Reinbek, St. Adolf-Stift
Reinbek, Germany
Robert-Bosch-Krankenhaus, Abt. Kardiologie / Pulmologie
Stuttgart, Germany, 70376
Latvia
Latvian Center of Cardiology, P. Stradins Clinical University Hospital
Riga, Latvia, LV1002
Lithuania
Kaunas Medical University Hospital - Department of Cardiology
Kaunas, Lithuania
Klaipeda Seamen's Hospital
Klaipeda, Lithuania
Vilnius University Hospital Santariskiu Clinic - Center of Cardiology and Angiology
Vilnius, Lithuania
Netherlands
WCN - Department of Cardiology Rijnstate Ziekenhuls
Arnhem, Netherlands, 6-800 TA
Catharina Ziekenhuis Eindhoven
Eindhoven, Netherlands, 5623EJ
Groene Hart Zeikenhhaus
Gouda, Netherlands, 2800BB
WCN - Bethesda ziekenhuis
Hoogeveen, Netherlands, 7909 AA
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands, 6229 HX
WCN - Canisius-Wilhelmina Ziekenhuis
Nijmegen, Netherlands, 6532 SZ
WCN - St. Franciscus Gasthuis
Rotterdam, Netherlands, 3045 PM
Poland
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
Okregowy Szpital Kolejowy w Lublinie Samodzielny
Lublin, Poland
Oddział Internistyczno-Kardiologiczny Samodzielny Publiczny Szpital Wojewódzki im. Jana Bożego w Lublinie
Lublin, Poland, 20-089
Oddzial Kardiologii Inwazyjnej Szpital Specjalistyczny im. E.Szczeklika w Tarnowie
Tarnow, Poland, 33-100
Oddział Kardiologiczno-Internistyczny Specjalistyczny Szpital Miejski im. Mikołaja Kopernika
Toruń, Poland, 87-100
Specjalistyczny Szpital Miejski im. Mikołaja Kopernika
Toruń, Poland, 87-100
Wojskowy Instytut Medyczny, CSK MON
Warszawa, Poland, 00-909
III Klinika Chorob Wewnetrznych i Kardiologii
Warszawa, Poland, 00-382
Klinika Kardiologii Zachowawczej Centralny Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji w Warszawie
Warszawa, Poland, 02-507
Osrodek Chorob Serca, Klinika Kardiologii, 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny
Wroclaw, Poland
Serbia
"Dedinje" Cardiovascular Institute
Belgrade, Serbia, 11040
Clinical Center of Serbia, Institute of CV Diseases
Belgrade, Serbia, 11000
Institute of Treatment and Reahabilitation 'Niska Banja'
Niska Banja, Serbia, 18205
Clinical Center Zemun, Dept. of Cardiology
Zemun, Serbia, 11080
Slovakia
Middle Slovak Institute of Cardiovascular Diseases (SUSCCH)
Banska Bysterica, Slovakia, 97401
NsP Prievidza so sidlom v Bojniciah
Bojnice, Slovakia, 97201
Slovensky ustav srdcovych a cevnych chorob
Bratislava, Slovakia, 83348
ICU, Hospital Lipt. Mikulas
Liptovsky Mikulas, Slovakia, 03101
FN - I. interna klinika
Nitra, Slovakia, 950 01
Liva - Central Military Hospital
Ruzomberok, Slovakia, 03401
Interna klinika FN Trnava, Fakultna nemocnica Trnava
Trnava, Slovakia, 91701
Internal Dep. Hospital Žilina
Žilina, Slovakia, 012 07
Sweden
Universitetssjukhuset MAS
Malmo, Sweden
Universityetssjukhuset, Orebro
Orebro, Sweden
Akademiska Sjukhuset, Uppsala
Uppsala, Sweden
Ukraine
Donetsk Regional Clinical Hospital
Donetsk, Ukraine
City Clinical Hospital #8
Kharkiv, Ukraine
Kiev City Clinical Hospital No 5, Coronary Care Unit
Kiev, Ukraine
City Clinical Hospital #1 Intensive Care Unit
Kiev, Ukraine
N.D. Strazhesko Institute of Cardiology Intensive Care Unit
Kiev, Ukraine
Lugansk First Clinical Multiprofile Hospital #1, Cardiology
Lugansk, 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
Sponsors and Collaborators
Cardiome Pharma
Investigators
Principal Investigator: 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
  More Information

No publications provided by Cardiome Pharma

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sheila Grant, VP Product Development and Product team leader, Vernakalant, Cardiome Pharma Corp.
ClinicalTrials.gov Identifier: NCT00668759     History of Changes
Other Study ID Numbers: VERI-305-AMIO
Study First Received: April 25, 2008
Last Updated: December 12, 2009
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Estonia: The State Agency of Medicine
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Ministry of Health
Slovakia: State Institute for Drug Control
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Sweden: Medical Products Agency
Ukraine: Ministry of Health

Keywords provided by Cardiome Pharma:
atrial fibrillation
atrial fib
AF

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Amiodarone
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on September 30, 2014