Antazoline in Rapid Cardioversion of Paroxysmal Atrial Fibrillation (AnPAF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Institute of Cardiology, Warsaw, Poland
Sponsor:
Information provided by (Responsible Party):
Institute of Cardiology, Warsaw, Poland
ClinicalTrials.gov Identifier:
NCT01527279
First received: February 2, 2012
Last updated: February 4, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Paroxysmal Atrial Fibrillation
Drug: antazoline
Drug: 0.9% saline
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Institute of Cardiology, Warsaw, Poland:

Primary Outcome Measures:
  • Conversion of AF to SN confirmed in standard 12-lead ECG during observation period after first iv bolus [ Time Frame: 1.5 hour ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to conversion of AF to SN [ Time Frame: 1.5 hour ] [ Designated as safety issue: No ]
    in minutes since first injection

  • Return of AF during observation period [ Time Frame: 1.5 hour ] [ Designated as safety issue: No ]
  • Serious adverse event defined as every adverse event requiring hospitalization or prolonged observation [ Time Frame: 1.5 hour ] [ Designated as safety issue: Yes ]
  • Arterial pressure < 90mmHg [ Time Frame: 1.5 hour ] [ Designated as safety issue: Yes ]
  • Disturbances of atrio-ventricular conduction [ Time Frame: 1.5 hour ] [ Designated as safety issue: Yes ]
  • Sustained supraventricular arrhythmia other than AF [ Time Frame: 1.5 hour ] [ Designated as safety issue: Yes ]
  • New complex ventricular arrhythmia [ Time Frame: 1.5 hour ] [ Designated as safety issue: Yes ]
    Ventricular arrhythmia other than premature ventricular contraction

  • Hot flush [ Time Frame: 1.5 hour ] [ Designated as safety issue: Yes ]
  • Drowsiness [ Time Frame: 1.5 hour ] [ Designated as safety issue: Yes ]
  • Headache [ Time Frame: 1.5 hour ] [ Designated as safety issue: Yes ]
  • Nausea/ vomiting [ Time Frame: 1.5 hour ] [ Designated as safety issue: Yes ]
  • Chest pain [ Time Frame: 1.5 hours ] [ Designated as safety issue: Yes ]
  • Tachycardia >180' [ Time Frame: 1.5 hours ] [ Designated as safety issue: Yes ]
  • Prolongation of QTc in ms (Bazett's formula) in comparison to baseline [ Time Frame: 1.5 hours ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 80
Study Start Date: November 2012
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 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.
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.
Experimental: 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.
Drug: 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.
Other Name: Phenazolinum

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01527279

Contacts
Contact: Aleksander Maciag, MD, PhD 022 343 40 50 ext +48 amaciag@ikard.pl
Contact: Michal M Farkowski, MD 022 343 40 50 ext +48 mfarkowski@gmail.com

Locations
Poland
Institute of Cardiology, II Dept. of Coronary Heart Disease Recruiting
Warsaw, Poland, 02-637
Contact: Aleksander Maciag, MD, PhD    022 343 4050 ext +48    amaciag@ikard.pl   
Contact: Michal M Farkowski, MD    022 343 4050 ext +48    mfarkowski@gmail.com   
Principal Investigator: Aleksander Maciag, MD, PhD         
Sub-Investigator: Michal M Farkowski, MD         
Sub-Investigator: Rafal Dabrowski, MD, PhD         
Sub-Investigator: Mariusz Pytkowski, MD, PhD         
Sponsors and Collaborators
Institute of Cardiology, Warsaw, Poland
Investigators
Study Chair: Hanna Szwed, MD, PhD Institute of Cardiology, Warsaw, Poland
Principal Investigator: Aleksander Maciag, MD, PhD Institute of Cardiology, Warsaw, Poland
Principal Investigator: Michal M Farkowski, MD Institute of Cardiology, Warsaw, Poland
  More Information

No publications provided by Institute of Cardiology, Warsaw, Poland

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Institute of Cardiology, Warsaw, Poland
ClinicalTrials.gov Identifier: NCT01527279     History of Changes
Other Study ID Numbers: Antazoline
Study First Received: February 2, 2012
Last Updated: February 4, 2013
Health Authority: Poland: The Central Register of Clinical Trials

Keywords provided by Institute of Cardiology, Warsaw, Poland:
atrial fibrillation
paroxysmal
cardioversion
antazoline

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Antazoline
Anti-Allergic Agents
Histamine Agents
Histamine Antagonists
Histamine H1 Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014