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

Sponsor:	Cardiome Pharma
Information provided by:	Cardiome Pharma
ClinicalTrials.gov Identifier:	NCT00668759

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
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:

Genetics Home Reference related topics: Brugada syndrome familial atrial fibrillation short QT syndrome

MedlinePlus related topics: Atrial Fibrillation

Drug Information available for: Amiodarone hydrochloride Amidox RSD 1235 Amiodarone

U.S. FDA Resources

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 ]

Estimated Enrollment:	240
Study Start Date:	April 2008
Estimated Study Completion Date:	October 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 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).
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: 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).

Arms

Assigned Interventions

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

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).

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:

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).

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

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

Contacts

Contact: Heather Kato, MAppSc	604-677-6905 ext 135	hkato@cardiome.com
Contact: Paul Holzapfel, RN, BSN	604-677-6905 ext 320	pholzapfel@cardiome.com

Show 100 Study Locations

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

Responsible Party:	Cardiome Pharma Corp. ( Dr Charles Fisher, Chief Medical Officer )
Study ID Numbers:	VERI-305-AMIO
Study First Received:	April 25, 2008
Last Updated:	October 13, 2009
ClinicalTrials.gov Identifier:	NCT00668759 History of Changes
Health Authority:	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 - French Health Products Safety Agency; Germany: Federal Institute for Drugs and Medical Devices; Lithuania: State Medicine Control Agency - Ministry of Health; Poland: Ministry of Health; Slovakia: State Institute for Drug Control; Sweden: Medical Products Agency; Ukraine: Ministry of Health

Keywords provided by Cardiome Pharma:

atrial fibrillation
atrial fib
AF

Additional relevant MeSH terms:

Vasodilator Agents
Heart Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Cardiovascular Agents
Amiodarone
Pharmacologic Actions

Pathologic Processes
Therapeutic Uses
Cardiovascular Diseases
Atrial Fibrillation
Anti-Arrhythmia Agents
Arrhythmias, Cardiac

ClinicalTrials.gov processed this record on November 27, 2009