A Phase III Superiority Study of Vernakalant vs Amiodarone in Subjects With Recent Onset Atrial Fibrillation (AVRO)
|Atrial Fibrillation||Drug: Vernakalant Injection Drug: Amiodarone Injection:||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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|
- 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. ]
- 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. ]
- 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. ]
- EQ-5D quality of life assessment. [ Time Frame: 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. [ 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. ]
|Study Start Date:||April 2008|
|Study Completion Date:||November 2009|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
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).
Active Comparator: 2
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).
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00668759
Show 100 Study Locations
|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|