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

Atrial Fibrillation Clinical Trial

— AVRO  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00668759
• Other study ID #: VERI-305-AMIO
• Status: Completed
• Phase: Phase 3
• First received: April 25, 2008
• Last updated: December 12, 2009
• Start date: April 2008
• Est. completion date: November 2009

Study information

• Verified date: December 2009
• Source: Cardiome Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Health CanadaCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyEstonia: The State Agency of MedicineFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: Ministry of HealthSlovakia: State Institute for Drug ControlSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSweden: Medical Products AgencyUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 254
• Est. completion date: November 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

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).
• 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).

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Hobart Hospital Cardiology Research	Hobart	Tasmania
Australia	Launceston General Hospital Cardiac Research Unit	Launceston	Tasmania
Australia	Royal Perth Hospital Emergency Research	Perth	Western Australia
Canada	Kingston General Hospital	Kingston	Ontario
Canada	Hopital de la Cite-de-la-Sante	Laval	Quebec
Canada	Centre Hopitalier de L'Universite de Montreal - Hotel Dieu	Montreal	Quebec
Canada	Institut de Cardiologie de Montreal	Montreal	Quebec
Canada	McGill University Health Center The Montreal General Hospital	Montreal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Centre de santé et de services sociaux du Sud de Lanaudière - Hôpital Pierre-Le Gardeur	Terrebonne	Quebec
Czech Republic	Mestrska nemocnice Caslav	Caslav
Czech Republic	Nemocnice Kromeríž	Kromeríž
Czech Republic	Nemocnice Kutna Hora s.r.o. Interni Oddeleni	Kutna Hora
Czech Republic	Nemocnice Decin Internal Medicine	Nove Mesto
Czech Republic	Fakultní nemocnice v Motole, KAR	Praha
Czech Republic	Ustredni vojenska nemocnice Koronarni jednotka	Praha
Czech Republic	VFN - III. Interni Klinika	Praha
Czech Republic	Oblastni nemocnice Pribram Interni Oddeleni	Pribram
Czech Republic	Nemocnice v Semilech Interní oddelení	Semily
Czech Republic	Nemocnice Slaný Interní oddelení	Slaný
Czech Republic	Nemocnice Tabor	Tabor
Czech Republic	Uherskohradistska nemocnice	Uherské Hradiste
Denmark	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
Estonia	Viimsi Hospital, Heart Clinic	Haabneeme
Estonia	Pärnu Hospital Department of Cardiology	Parnu
Estonia	East Tallinn Central Hospital-Clinic of Cardiology	Tallinn
Estonia	Tartu University Hospital Heart Clinic	Tartu
Finland	Oulu University Hospital - Dept of Internal Medicine	Oulu
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
Germany	Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin	Berlin
Germany	Charite Campus Mitte, Med. Klinik und Poliklinik mit Schwerpunkt Kardiologie und Angiologie	Berlin
Germany	Herzzentrum Brandenburg in Bernau Innere Medizin	Bernau
Germany	Universitätsklinikum Bonn, Med. Klinik und Poliklinik II	Bonn
Germany	Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie	Frankfurt
Germany	Universitatsklinikum Gottingen, Herzzentrum	Gottingen
Germany	Martin-Luther Universitat Halle, Med. Klinik und Poliklinik III- Fachrichtung Kardiologie	Halle
Germany	Klinik Hamburg Bambek Kardiologie	Hamburg
Germany	Medizinisches Versorgungszentrum Prof. Mathey, Prof. Schofer GmbH	Hamburg
Germany	Medizinische Klinik, Klinikum Hannover Nordstadt	Hannover
Germany	Ambulantes Herzzentrum Kassel Innere Medizin	Kassel
Germany	Klinikum der Universität Köln, Medizinische Klinik III	Köln
Germany	Klinikum der Stadt Ludwigshafen am Rhein gGmbH	Ludwigshafen
Germany	Carl-von Basedow-Klinikum Merseburg	Merseburg
Germany	Klinikum Pirna GmbH, Innere Medizin II, Kardiologie	Pirna
Germany	Krankenhaus Reinbek, St. Adolf-Stift	Reinbek
Germany	Robert-Bosch-Krankenhaus, Abt. Kardiologie / Pulmologie	Stuttgart
Latvia	Latvian Center of Cardiology, P. Stradins Clinical University Hospital	Riga
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
Netherlands	WCN - Department of Cardiology Rijnstate Ziekenhuls	Arnhem
Netherlands	Catharina Ziekenhuis Eindhoven	Eindhoven
Netherlands	Groene Hart Zeikenhhaus	Gouda
Netherlands	WCN - Bethesda ziekenhuis	Hoogeveen
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	WCN - Canisius-Wilhelmina Ziekenhuis	Nijmegen
Netherlands	WCN - St. Franciscus Gasthuis	Rotterdam
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	Oddzial Internistyczno-Kardiologiczny Samodzielny Publiczny Szpital Wojewódzki im. Jana Bozego w Lublinie	Lublin
Poland	Okregowy Szpital Kolejowy w Lublinie Samodzielny	Lublin
Poland	Oddzial Kardiologii Inwazyjnej Szpital Specjalistyczny im. E.Szczeklika w Tarnowie	Tarnow
Poland	Oddzial Kardiologiczno-Internistyczny Specjalistyczny Szpital Miejski im. Mikolaja Kopernika	Torun
Poland	Specjalistyczny Szpital Miejski im. Mikolaja Kopernika	Torun
Poland	III Klinika Chorob Wewnetrznych i Kardiologii	Warszawa
Poland	Klinika Kardiologii Zachowawczej Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie	Warszawa
Poland	Wojskowy Instytut Medyczny, CSK MON	Warszawa
Poland	Osrodek Chorob Serca, Klinika Kardiologii, 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny	Wroclaw
Serbia	"Dedinje" Cardiovascular Institute	Belgrade
Serbia	Clinical Center of Serbia, Institute of CV Diseases	Belgrade
Serbia	Institute of Treatment and Reahabilitation 'Niska Banja'	Niska Banja
Serbia	Clinical Center Zemun, Dept. of Cardiology	Zemun
Slovakia	Internal Dep. Hospital Žilina	Žilina
Slovakia	Middle Slovak Institute of Cardiovascular Diseases (SUSCCH)	Banska Bysterica
Slovakia	NsP Prievidza so sidlom v Bojniciah	Bojnice
Slovakia	Slovensky ustav srdcovych a cevnych chorob	Bratislava
Slovakia	ICU, Hospital Lipt. Mikulas	Liptovsky Mikulas
Slovakia	FN - I. interna klinika	Nitra
Slovakia	Liva - Central Military Hospital	Ruzomberok
Slovakia	Interna klinika FN Trnava, Fakultna nemocnica Trnava	Trnava
Sweden	Universitetssjukhuset MAS	Malmo
Sweden	Universityetssjukhuset, Orebro	Orebro
Sweden	Akademiska Sjukhuset, Uppsala	Uppsala
Ukraine	Donetsk Regional Clinical Hospital	Donetsk
Ukraine	City Clinical Hospital #8	Kharkiv
Ukraine	City Clinical Hospital #1 Intensive Care Unit	Kiev
Ukraine	Kiev City Clinical Hospital No 5, Coronary 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

Sponsors (1)

Lead Sponsor	Collaborator
Cardiome Pharma

Countries where clinical trial is conducted

Australia,  Canada,  Czech Republic,  Denmark,  Estonia,  Finland,  France,  Germany,  Latvia,  Lithuania,  Netherlands,  Poland,  Serbia,  Slovakia,  Sweden,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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.	No
Secondary	Proportion of subjects with symptom relief at 90 minutes after the start of infusion.		Relief of AF symptoms 90 minutes after start of infusion.	No
Secondary	EQ-5D quality of life assessment.		Assessment of quality of life 2 hours after start of infusion.	No
Secondary	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.	Yes