Paroxysmal Atrial Fibrillation
Conditions
Keywords
atrial fibrillation, paroxysmal, cardioversion, antazoline
Brief summary
The purpose of this randomized, double blind, placebo-controlled, superiority clinical trial was to assess clinical efficacy of antazoline in rapid conversion of atrial fibrillation during observation sinus rhythm.
Detailed description
Antazoline is a first generation antihistaminic agent with chinidin-like properties. When administered intravenously, antazoline exerts a strong antiarrhythmic effect on supraventricular arrhythmia especially on atrial fibrillation (AF) facilitating rapid conversion to sinus rhythm. Despite relative lack of published data antazoline is marketed in Poland and widely used in cardiology wards and emergency rooms due to its efficacy, safety and rapid onset of action within minutes of administration. To show superiority of antazoline over placebo a sample size of 80 patients was calculated based on following assumptions: two-tailed test, a type I error of 0.01, a power of 90%, efficacy of placebo 5%, efficacy of antazoline 50% and 20% drop-out rate to fulfill the criteria of intention-to-treat analysis. Due to presumed lack of statistical power the secondary end points and safety endpoints will be considered exploratory.
Interventions
DRUGantazoline
Patients assigned to antazoline group will be administered antazoline in boluses of 50mg diluted to 10cm3 every 5 minutes up to cumulative dose of 250mg or conversion of AF to SN. Drug administration will also be stopped in case of serious adverse event or conversion of AF to different supraventricular arrhythmia. BP will be measured before every injection.
DRUG0.9% saline
Patients assigned to control group will be administered 0.9% saline in boluses of 10cm3 every 5 minutes up to cumulative volume of 50cm3, conversion of AF to SN or in case of serious adverse event or conversion of AF to different supraventricular arrhythmia. BP will be measured before every injection.
Sponsors
National Institute of Cardiology, Warsaw, Poland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent for participating in the study and written standard version of informed consent for cardioversion accepted in Institute of Cardiology, Warsaw, Poland * Age above 18 and good general condition * Potassium level over 3.5 mmol/l * Stable cardio-pulmonary state on enrollment * In case of unclear history of heart failure or suspicion of impaired left ventricle function echocardiography is indicated prior to enrollment * A long-term antiarrhythmic drug therapy is allowed
Exclusion criteria
* Lack of written informed consent * Antazoline allergy * AF related to significant valvular disease * Clinically significant heart failure or ejection fraction \< 55% * Diastolic blood pressure (BP) \< 100mmHg * History of significant bradyarrhythmia not treated with permanent pacemaker * QT prolongation over 440ms or QTc (Bazett's formula) over population norm * Tachycardia \> 160' * Advanced liver or kidney failure * Acute coronary syndrome, coronary artery by-pass graft, stroke or transient ischemic attack within 30 days before enrollment * Preexcitation in ECG not treated by radiofrequency ablation of accessory pathway * Signs and symptoms of ischemia related to AF * An investigational drug used within 30 days before enrollment * Pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Conversion of AF to SN confirmed in standard 12-lead ECG during observation period after first iv bolus | 1.5 hour |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Return of AF during observation period | 1.5 hour | — |
| Serious adverse event defined as every adverse event requiring hospitalization or prolonged observation | 1.5 hour | — |
| Arterial pressure < 90mmHg | 1.5 hour | — |
| Disturbances of atrio-ventricular conduction | 1.5 hour | — |
| Sustained supraventricular arrhythmia other than AF | 1.5 hour | — |
| New complex ventricular arrhythmia | 1.5 hour | Ventricular arrhythmia other than premature ventricular contraction |
| Time to conversion of AF to SN | 1.5 hour | in minutes since first injection |
| Drowsiness | 1.5 hour | — |
| Headache | 1.5 hour | — |
| Nausea/ vomiting | 1.5 hour | — |
| Chest pain | 1.5 hours | — |
| Tachycardia >180' | 1.5 hours | — |
| Prolongation of QTc in ms (Bazett's formula) in comparison to baseline | 1.5 hours | — |
| Hot flush | 1.5 hour | — |
Countries
Poland
Outcome results
None listed