A Phase III Prospective, Randomized, Double-Blind, Active-Controlled, Multi-Center, Superiority Study of Vernakalant Injection versus Amiodarone in Subjects with Recent Onset Atrial Fibrillatio

• Conditions: Treatment of Atrial fibrillation (AF). AF is the most common arrhythmia encountered in clinical practice. It is usually associated with age and general physical condition, rather than with a specific cardiac event as is often the case with ventricular arrhythmia. Although not directly life-threatening, atrial arrhythmias can cause discomfort, lead to stroke or congestive heart failure, increase overall morbidity and are costly to health care systems due to hospitalizations.; MedDRA version: 9.1Level: LLTClassification code 10003658Term: Atrial fibrillation

• Registration Number: EUCTR2007-005625-29-FI
• Lead Sponsor: Cardiome Pharma Corp.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09-08
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

Subjects must:
1. Have symptomatic AF of 3 to 48 hours duration at baseline.
2. Be eligible for cardioversion.
3. Be 18 to 85 years of age.
4. Comprehend and sign a written informed consent form (compliant with applicable
regulatory requirements, such as the EU Privacy Directive as implemented by member states in national law, or the Personal Information Protection and Electronic Documents Act, Canada, as applicable).
5. Women must not be pregnant, be non-nursing, and if pre-menopausal, must be using an effective form of birth control from time of screening until 3 months after discharge. Methods of birth control considered to be effective may include hormonal contraception (the pill), an intrauterine device (IUD), condoms in combination with a spermicidal cream, total abstinence or sterilization. Men should be advised not to conceive a child and are advised to use an effective form of birth control from admission until 3 months after discharge.
6. Have adequate anticoagulation therapy for cardioversion in accordance with standard of practice as recommended by ACC/AHA/ESC guidelines.
7. 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. Baseline blood pressure will be measured 3 times within 5 minutes, after resting supine for 5 minutes, and averaged to determine the baseline BP.
8. Have a body weight between 45 and 136 kg (99 and 300 lbs). For subjects weighing >113 kg (250 lbs), the vernakalant dose should be based on a weight of 113 kg (250 lbs) and not higher.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects must not have:
1. 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). 2. Symptomatic bradycardia, sick sinus syndrome, or ventricular rate less than 50 beats per minute (bpm) as documented by 12-lead ECG at screening.
3. A QRS interval >140 msec.
4. Any known concurrent temporary secondary causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, pneumonia, acute pericarditis, myocarditis, or hypoxemia (oxygen saturation less than 90% on room air).
5. Atrial flutter.
6. Significant valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis.
7. Documented previous episodes of second or third degree atrioventricular (AV) block.
8. Had a myocardial infarction (MI), acute coronary syndrome or cardiac surgery within 30 days prior to entry into the study.
9. Uncorrected electrolyte imbalance of serum potassium (K+) <3.5 mmol/L or >5.5 mmol/L or magnesium (Mg2+) below the lower limit of normal (Mg2+< 0.65 mmol/L in subjects 65 years or younger and <0.80 mmol/L in subjects 66 years or older). Both K+ and Mg2+ must be corrected prior to dosing.
10. Clinical evidence of digoxin toxicity in the opinion of the Investigator.
11. Failed electrical cardioversion during current episode of AF.
12. Received intravenous Class I or Class III antiarrhythmic drugs within 24 hours prior to dosing.
13. Received any oral Class I or Class III antiarrhythmic drugs for the purpose of conversion of AF to sinus rhythm within 24 hours prior to dosing.
14. Received amiodarone injection within 30 days prior to dosing, or oral amiodarone within 90 days prior to dosing.
15. A pacemaker.
16. Unstable congestive heart failure (CHF), Class IV CHF, or CHF requiring inotropes.
17. Serious pulmonary, hepatic, metabolic, renal, gastrointestinal, central nervous system or psychiatric disease, infection, febrile illness (oral temperature > 38.5°C), end stage disease states, or any other disease that could interfere with the conduct or validity of the study or compromise subject safety.
18. Have any evidence of an atrial thrombus.
19. Troponin (I or T) levels above the upper limit of normal.
20. Had a cerebrovascular accident within past 3 months.
21. Any other surgical or medical condition that, in the judgment of the clinical Investigator might warrant exclusion or be contraindicated for safety reasons.
22. Thyroid dysfunction, hypersensitivity to iodine, or any other condition for which amiodarone injection is contraindicated.
23. Had previous exposure to vernakalant.
24. Have known or suspected hypersensitivity to vernakalant injection or any component of its formulation, or amiodarone injection or any component of its formulation.
25. Be concurrently participating in another drug study or have received an investigational drug within 30 days prior to screening.
26. Be unable to communicate well with the Investigator and to comply with the requirements of the entire study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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. ;Secondary Objective: The secondary objective is to compare the safety of vernakalant to amiodarone.;Primary end point(s): Proportion of subjects with conversion of AF to SR within 90 minutes after the start of infusion.