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Antazoline in Rapid Cardioversion of Paroxysmal Atrial Fibrillation

Phase 4
Completed
Conditions
Paroxysmal Atrial Fibrillation
Interventions
Drug: 0.9% saline
Registration Number
NCT01527279
Lead Sponsor
National Institute of Cardiology, Warsaw, Poland
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
74
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo0.9% salineAny patient fulfilling the inclusion criteria will be prepared to pharmacological cardioversion in a standard way comprising of standard baseline 12-lead ECG, continuous ECG monitoring, periodic noninvasive blood pressure monitoring (BP) and iv line. After drug administration the patient will be observed for 1.5 hour after the last dose with exit ECG and BP measure taken at the end of observation. Further treatment of the patient depends on clinical state and follows appropriate clinical guidelines.
AntazolineantazolineAny patient fulfilling the inclusion criteria will be prepared to pharmacological cardioversion in a standard way comprising of standard baseline 12-lead ECG, continuous ECG monitoring, periodic noninvasive blood pressure monitoring (BP) and iv line. After drug administration the patient will be observed for 1.5 hour after the last dose with exit ECG and BP measure taken at the end of observation. Further treatment of the patient depends on clinical state and follows appropriate clinical guidelines.
Primary Outcome Measures
NameTimeMethod
Conversion of AF to SN confirmed in standard 12-lead ECG during observation period after first iv bolus1.5 hour
Secondary Outcome Measures
NameTimeMethod
Hot flush1.5 hour
Time to conversion of AF to SN1.5 hour

in minutes since first injection

Arterial pressure < 90mmHg1.5 hour
Nausea/ vomiting1.5 hour
Chest pain1.5 hours
Tachycardia >180'1.5 hours
Sustained supraventricular arrhythmia other than AF1.5 hour
Drowsiness1.5 hour
Headache1.5 hour
Return of AF during observation period1.5 hour
Serious adverse event defined as every adverse event requiring hospitalization or prolonged observation1.5 hour
Disturbances of atrio-ventricular conduction1.5 hour
New complex ventricular arrhythmia1.5 hour

Ventricular arrhythmia other than premature ventricular contraction

Prolongation of QTc in ms (Bazett's formula) in comparison to baseline1.5 hours

Trial Locations

Locations (1)

Institute of Cardiology, II Dept. of Coronary Heart Disease

🇵🇱

Warsaw, Poland

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