Antazoline in Rapid Cardioversion of Paroxysmal Atrial Fibrillation

NCT ID: NCT01527279

Last Updated: 2015-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2015-03-31

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.

Conditions

Paroxysmal Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Any 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.

Group Type: PLACEBO_COMPARATOR

0.9% saline

Intervention Type: DRUG

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.

Antazoline

Any 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.

Group Type: EXPERIMENTAL

antazoline

Intervention Type: DRUG

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.

Interventions

antazoline

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.

Intervention Type: DRUG

0.9% 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.

Intervention Type: DRUG

Other Intervention Names

Phenazolinum

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Cardiology, Warsaw, Poland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hanna Szwed, MD, PhD

Role: STUDY_CHAIR

National Institute of Cardiology, Warsaw, Poland

Aleksander Maciag, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Institute of Cardiology, Warsaw, Poland

Michal M Farkowski, MD

Role: PRINCIPAL_INVESTIGATOR

National Institute of Cardiology, Warsaw, Poland

Locations

Institute of Cardiology, II Dept. of Coronary Heart Disease

Warsaw, , Poland

Countries

Poland

References

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.

Reference Type: BACKGROUND

PMID: 22967497 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28339554 (View on PubMed)

Other Identifiers

Antazoline

Identifier Type: -

Identifier Source: org_study_id