Clinical trial NCT01527279: Antazoline in Rapid Cardioversion of Paroxysmal Atrial Fibrillation
Official title: Clinical Efficacy of Antazoline in Rapid Cardioversion of Paroxysmal Atrial Fibrillation - a Single Centre, Randomized, Double-blind, Placebo-controlled Study (the AnPAF Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Paroxysmal Atrial Fibrillation
Keywords: atrial fibrillation
paroxysmal
cardioversion
antazoline
Lead sponsor: National Institute of Cardiology, Warsaw, Poland
Sponsor class: OTHER
First posted: 2012-02-07
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Conversion of AF to SN confirmed in standard 12-lead ECG during observation period after first iv bolus
timeFrame: 1.5 hour
Secondary outcomes:
measure: Time to conversion of AF to SN
timeFrame: 1.5 hour
measure: Return of AF during observation period
timeFrame: 1.5 hour
measure: Serious adverse event defined as every adverse event requiring hospitalization or prolonged observation
timeFrame: 1.5 hour
measure: Arterial pressure < 90mmHg
timeFrame: 1.5 hour
measure: Disturbances of atrio-ventricular conduction
timeFrame: 1.5 hour
measure: Sustained supraventricular arrhythmia other than AF
timeFrame: 1.5 hour
measure: New complex ventricular arrhythmia
timeFrame: 1.5 hour
measure: Hot flush
timeFrame: 1.5 hour
measure: Drowsiness
timeFrame: 1.5 hour
measure: Headache
timeFrame: 1.5 hour
measure: Nausea/ vomiting
timeFrame: 1.5 hour
measure: Chest pain
timeFrame: 1.5 hours
measure: Tachycardia >180'
timeFrame: 1.5 hours
measure: Prolongation of QTc in ms (Bazett's formula) in comparison to baseline
timeFrame: 1.5 hours
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: Institute of Cardiology, II Dept. of Coronary Heart Disease
Study officials:
affiliation: National Institute of Cardiology, Warsaw, Poland
name: Hanna Szwed, MD, PhD
role: STUDY_CHAIR
affiliation: National Institute of Cardiology, Warsaw, Poland
name: Aleksander Maciag, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute of Cardiology, Warsaw, Poland
name: Michal M Farkowski, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Farkowski MM, Maciag A, Dabrowski R, Pytkowski M, Kowalik I, Szwed H. Clinical efficacy of antazoline in rapid cardioversion of paroxysmal atrial fibrillation--a protocol of a single center, randomized, double-blind, placebo-controlled study (the AnPAF Study). Trials. 2012 Sep 11;13:162. doi: 10.1186/1745-6215-13-162.
citation: Maciag A, Farkowski MM, Chwyczko T, Beckowski M, Syska P, Kowalik I, Pytkowski M, Wozniak J, Dabrowski R, Szwed H. Efficacy and safety of antazoline in the rapid cardioversion of paroxysmal atrial fibrillation (the AnPAF Study). Europace. 2017 Oct 1;19(10):1637-1642. doi: 10.1093/europace/euw384.