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

Primary Purpose

Atrial Fibrillation

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Vernakalant Injection

Amiodarone Injection:

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring atrial fibrillation, atrial fib, AF

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Royal Adelaide Hospital
Royal Hobart Hospital Cardiology Research
Launceston General Hospital Cardiac Research Unit
Royal Perth Hospital Emergency Research
Kingston General Hospital
The Ottawa Hospital
Hopital de la Cite-de-la-Sante
Institut de Cardiologie de Montreal
Centre Hopitalier de L'Universite de Montreal - Hotel Dieu
McGill University Health Center The Montreal General Hospital
Centre de santé et de services sociaux du Sud de Lanaudière - Hôpital Pierre-Le Gardeur
Mestrska nemocnice Caslav
Nemocnice Kroměříž
Nemocnice Kutna Hora s.r.o. Interni Oddeleni
Nemocnice Decin Internal Medicine
Fakultní nemocnice v Motole, KAR
Ustredni vojenska nemocnice Koronarni jednotka
VFN - III. Interni Klinika
Oblastni nemocnice Pribram Interni Oddeleni
Nemocnice v Semilech Interní oddělení
Nemocnice Slaný Interní oddělení
Nemocnice Tabor
Uherskohradistska nemocnice
Gentofte Amtssygehus Kardiologisk afdeling
Herlev Amtssygehus, Kardiologisk
Sygehus Vendsyssel Hjorring
Roskilde Amts Sygehus Køge
Regionshospitalet Silkeborg
Viimsi Hospital, Heart Clinic
Pärnu Hospital Department of Cardiology
East Tallinn Central Hospital-Clinic of Cardiology
Tartu University Hospital Heart Clinic
Oulu University Hospital - Dept of Internal Medicine
Hopital Trousseau - Service de Cardiologie
CHU de Nancy - Hopital Brabois - Service de Cardiologie
Hôpital Lariboisiere
CHU de Strasbourg - Hopital Hautepierre - Service de Cardiologie
Charite Campus Mitte, Med. Klinik und Poliklinik mit Schwerpunkt Kardiologie und Angiologie
Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin
Herzzentrum Brandenburg in Bernau Innere Medizin
Universitätsklinikum Bonn, Med. Klinik und Poliklinik II
Johann Wolfgang Goethe Universitaet Med Klinik III - Kardiologie
Universitatsklinikum Gottingen, Herzzentrum
Martin-Luther Universitat Halle, Med. Klinik und Poliklinik III- Fachrichtung Kardiologie
Klinik Hamburg Bambek Kardiologie
Medizinisches Versorgungszentrum Prof. Mathey, Prof. Schofer GmbH
Medizinische Klinik, Klinikum Hannover Nordstadt
Ambulantes Herzzentrum Kassel Innere Medizin
Klinikum der Universität Köln, Medizinische Klinik III
Klinikum der Stadt Ludwigshafen am Rhein gGmbH
Carl-von Basedow-Klinikum Merseburg
Klinikum Pirna GmbH, Innere Medizin II, Kardiologie
Krankenhaus Reinbek, St. Adolf-Stift
Robert-Bosch-Krankenhaus, Abt. Kardiologie / Pulmologie
Latvian Center of Cardiology, P. Stradins Clinical University Hospital
Kaunas Medical University Hospital - Department of Cardiology
Klaipeda Seamen's Hospital
Vilnius University Hospital Santariskiu Clinic - Center of Cardiology and Angiology
WCN - Department of Cardiology Rijnstate Ziekenhuls
Catharina Ziekenhuis Eindhoven
Groene Hart Zeikenhhaus
WCN - Bethesda ziekenhuis
Academisch Ziekenhuis Maastricht
WCN - Canisius-Wilhelmina Ziekenhuis
WCN - St. Franciscus Gasthuis
Oddzial Kardiologiczny Wielospecjalityczny Szpital Miejski im.
Szpital Miejski im. J. Brudzinskiego Oddzial Kardiologii
Klinika Chorob Wewnetrznych z Oddzialem Farmakologii Klinicznej i Terapii Monitorowanej
Oddział Internistyczno-Kardiologiczny Samodzielny Publiczny Szpital Wojewódzki im. Jana Bożego w Lublinie
Okregowy Szpital Kolejowy w Lublinie Samodzielny
Oddzial Kardiologii Inwazyjnej Szpital Specjalistyczny im. E.Szczeklika w Tarnowie
Oddział Kardiologiczno-Internistyczny Specjalistyczny Szpital Miejski im. Mikołaja Kopernika
Specjalistyczny Szpital Miejski im. Mikołaja Kopernika
III Klinika Chorob Wewnetrznych i Kardiologii
Wojskowy Instytut Medyczny, CSK MON
Klinika Kardiologii Zachowawczej Centralny Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji w Warszawie
Osrodek Chorob Serca, Klinika Kardiologii, 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny
Clinical Center of Serbia, Institute of CV Diseases
"Dedinje" Cardiovascular Institute
Institute of Treatment and Reahabilitation 'Niska Banja'
Clinical Center Zemun, Dept. of Cardiology
Middle Slovak Institute of Cardiovascular Diseases (SUSCCH)
NsP Prievidza so sidlom v Bojniciah
Slovensky ustav srdcovych a cevnych chorob
ICU, Hospital Lipt. Mikulas
FN - I. interna klinika
Liva - Central Military Hospital
Interna klinika FN Trnava, Fakultna nemocnica Trnava
Internal Dep. Hospital Žilina
Universitetssjukhuset MAS
Universityetssjukhuset, Orebro
Akademiska Sjukhuset, Uppsala
Donetsk Regional Clinical Hospital
City Clinical Hospital #8
City Clinical Hospital #1 Intensive Care Unit
Kiev City Clinical Hospital No 5, Coronary Care Unit
N.D. Strazhesko Institute of Cardiology Intensive Care Unit
Lugansk First Clinical Multiprofile Hospital #1, Cardiology
Lviv Reg St Clinical Treat-and-Diagn Cardio. Centre Dept of Myocardial Infarction
City Clinical Hospital #9 Dept of Arrhythmia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Proportion of subjects with conversion of atrial fibrillation to sinus rhythm within 90 minutes after the start of infusion.

Secondary Outcome Measures

Time to conversion within 90 minutes after the start of infusion.

Proportion of subjects with symptom relief at 90 minutes after the start of infusion.

EQ-5D quality of life assessment.

Monitoring of adverse events, vital signs, continuous telemetry monitoring, 12-lead Holter monitoring, 12-lead ECGs, and laboratory tests.

Full Information

NCT ID

NCT00668759

First Posted

April 25, 2008

Last Updated

December 12, 2009

Sponsor

Advanz Pharma

1. Study Identification

Unique Protocol Identification Number

NCT00668759

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2009

Overall Recruitment Status

Completed

Study Start Date

April 2008 (undefined)

Primary Completion Date

October 2009 (Actual)

Study Completion Date

November 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Advanz Pharma

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atrial Fibrillation

Keywords

atrial fibrillation, atrial fib, AF

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

254 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Arm Title

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Vernakalant Injection

Other Intervention Name(s)

RSD1235, Kynapid

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Amiodarone Injection:

Other Intervention Name(s)

Amiodarone, Cordarone

Intervention Description

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).

Primary Outcome Measure Information:

Title

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.

Secondary Outcome Measure Information:

Title

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.

Title

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.

Title

EQ-5D quality of life assessment.

Time Frame

Assessment of quality of life 2 hours after start of infusion.

Title

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

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.

Overall Study Officials: