Atrial FibrillationPhase 4AnProAFNCT05720572
Antazoline in Comparison to Propafenone in Pharmacological Cardioversion of Atrial Fibrillation.
A Phase 4 study testing Antazoline and Propafenone in people with Atrial Fibrillation, run by Centre of Postgraduate Medical Education at 1 site in Poland.
Trial summary
The purpose of this randomized, double blind, non-inferiority clinical trial was to compare the clinical efficacy and safety of antazoline with propafenone in the rapid conversion of paroxysmal non-valvular atrial fibrillation to sinus rhythm in patients without heart failure Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Antazoline and Propafenone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 1 sitePoland
- Study dates
- 1 Sep 2019to 1 Jan 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent for participating in the study and written standard version of informed consent for cardioversion accepted at the Department of Heart Disease, Warsaw, Poland
- Age 18 to 90years
- AF lasting < 48 hours
- Stable cardio-pulmonary state on enrollment
- In case of unclear history of heart failure or suspicion of left ventricle damage echocardiographyis indicated prior to enrollment
Who cannot join
- Lack of written informed consent
- Allergy to antazoline or propafenone
- Intolerance of anatzoline or propafenone
- AF related to significant valvular disease
- Clinically significant heart failure or ejection fraction <50%
- Systolic blood pressure (BP) <100 mmHg
Show all 19Show fewer
- History of significant bradyarrhythmia not treatedwith permanent pacemaker
- Resting ventricular rate of < 80 bpm without pacemaker backup
- Heart rate > 140 bpm
- Tachycardia >160'
- Advanced liver or kidney failure
- Acute coronary syndrome, coronary artery by-passgraft, 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
- Advanced liver or kidney failure
- QT prolongation over 440 ms or QTc (Bazett's formula) over the population norm
- Pregnancy or breast feeding
- Background therapy of any oral AADs.
Trial locations and contacts
1 site in 1 country.
Poland1 site, 1 recruiting
- Recruiting
Postgraduate Medical School
Warsaw, 00-685
Jarosław JK Karwowski, PhD, +48502913169, karwowski.jarek@gmail.com
About this study
Official title: Clinical Efficacy and Safety of Antazoline in Comparison to Propafenone in Conversion of Paroxysmal Atrial Fibrillation to Sinus Rhythm - a Single Center, Randomized, Double-blinded Study (the AnProAF Study).
The purpose of this randomized, double blind, non-inferiority clinical trial was to compare the clinical efficacy and safety of antazoline with propafenone in the rapid conversion of paroxysmal non-valvular atrial fibrillation to sinus rhythm in patients without heart failure
Read the detailed description
Background
Atrial fibrillation (AF) is the most common type of arrhythmia, and occurs in approximately 3% of the population over 20 years of age and 9% of those over 80 years of age [1]. Restoration of sinus rhythm (SR) remains an integral part of the treatment for this type of arrhythmia. Early pharmacological (PCV) or electrical cardioversion (ECV) is necessary to improve symptoms, prevent the side effects of the prolonged crisis of arrhythmia, and avoid hospitalization. ECV requires general sedation and does not prevent from immediate AF recurrence. Therefore, the majority of patients are qualified for pharmacological attempts to terminate the arrhythmia. The early PCV of AF to SR may be achieved by administration of Class (Vaughan-Williams) IA, IC, and III antiarrhythmic drugs (AADs): flecainide, ibutilide, dofetilide, propafenone, amiodarone, or novel agent vernakalant. These AADs have limitations such as proarrhythmic side effects in patients with structural heart disease (IC), delayed onset of action (amiodarone), high cost, and low availability (vernakalant) [1].
An efficacious, well-tolerated, less expensive antiarrhythmic drug with rapid onset of action is necessary. Antazoline meslate is an antihistaminic agent with antiarrhythmic quinidine-like properties, which have been documented in 1960s [2,3]. Electrophysiologically, antazoline prolongs action potential duration and lowers its amplitude, prolongs phase-0 duration, reduces phase-4 of resting potential, and reduces excitability of cardiac tissue. Anticholinergic action of this drug leads to transient increase of heart rate, improving atrioventricular conduction and increasing the corrected QT-interval, left atrial refractory period, and inter-atrial conduction time [4-6]. In human healthy volunteers, the terminal elimination half-life of antazoline was 2.29 hours with a mean residence time of 3.45 hours [7]. In clinical practice, the drug can be administered intravenously in boluses of 50-100 mg every 3-5 minutes until successful cardioversion or up to a cumulative dose of 250-350 mg [8].
In Poland, it was registered for intravenous termination of supraventricular arrhythmias. Unfortunately, antazoline is not listed in any of the formal guidelines due to the lack of large randomized trials comparing this drug with other AADs in SR restoration. To the best of our knowledge, only one randomized clinical trial has been published that evaluated the antiarrhythmic effect of antazoline in comparison to placebo [9]. In antazoline group (38 patients), successful conversion of AF to SR was achieved in 72.2%, with a median duration of 16 minutes. Other published observational studies have shown high efficacy of antazoline, ranging between 50% and 80% and a rapid onset of action with cardioversion duration between 7 and 20 minutes [3,8,10-14]. The aim of this randomized, double blind, placebo-controlled, non-inferiority clinical trial is to assess clinical efficacy of antazoline in rapid conversion of atrial fibrillation to sinus rhythm in patients with paroxysmal atrial fibrillation without significant valvular disease or advanced heart failure.
Methods Study objectives The purpose of the study is to assess clinical efficacy of antazoline in rapid conversion of AF to SR in comparison to propafenone in patients with paroxysmal atrial fibrillation without significant valvular disease or advanced heart failure. Due to a presumed lack of statistical power, secondary end points and safety analysis will be considered exploratory.
Study design This randomized, double-blind, placebo-controlled, non-inferiority clinical study is actually carried out at the Department of Heart Disease, Centre of Postgraduate Medical Education, Warsaw, Poland. The study will include 390 participants presenting with an episode of AF lasting less than 48 h. All participants must sign an informed consent form. Approval for the study was obtained from the local ethics committee (nr 85/PB/2019; July 10, 2019).
The study protocol was approved by the local ethics committee and is in full compliance with the Declaration of Helsinki.
- Conditions
- Atrial Fibrillation
- Being tested
- Antazoline, Propafenone
- Keywords
- Antazoline, Antiarrhythmic drugs, Pharmacological cardioversion, Atrial fibrillation, Randomized controlled trial
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AntazolineDrug
Participants assigned to the antazoline group will be administered antazoline in boluses in boluses of 100 mg diluted to 20 cm3 every 10 minutes up to a total dose of 300 mg diluted to 60 cm3 or conversion of AF to SR. Drug administration will also be stopped in case of an adverse event or conversion of AF to a different supraventricular arrhythmia. BP will be measured before every injection.
PropafenoneDrug
Patients assigned to the propafenone group were administered three 20-cm3 boluses every 10 minutes up to 60 cm3 or conversion of AF to SR. Each of the first two boluses included 70 mg propafenone (total dose 140 mg), and the third bolus contained only 20-cm3 0.9% NaCl. Drug administration will be stopped in case of an adverse event or conversion of AF to a different supraventricular arrhythmia. BP will be measured before every injection.
| Study group | Role | What they receive |
|---|---|---|
| Antazoline | Experimental | 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 3 hours after the first 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. Receives: Drug: Antazoline |
| Propafenone | Active comparator | 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 3 hours after the first 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. Receives: Drug: Propafenone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conversion of atrial fibrillation (AF) to sinus rhythm (SR)
Conversion of AF to SR confirmed in standard 12-lead ECG during the observation period
Measured: 3 hours
Secondary outcomes (14)
Time to conversion of atrial fibrillation to sinus rhythm
Measured: 3 hours
Serious adverse event defined as every adverse event requiring hospitalization or prolonged observation
Measured: 3 hours
Disturbances of atrioventricular conduction
Measured: 3 hours
Hypotension < 90mmHg
Measured: 3 hours
Pauses > 4s
Pauses in heart beat
Measured: 3 hours
Tachycardia > 180bpm
Measured: 3 hours
Nausea and/or vomiting
Measured: 3 hours
Hot flush
Measured: 3 hours
Drowsiness
Measured: 3 hours
Headache
Measured: 3 hours
Bitter/metallic taste
Measured: 3 hours
Anxiety
Measured: 3 hours
New complex ventricular arrhythmia
Measured: 3 hours
Prolongation of QTc in ms (Bazett's formula) in comparison to baseline
Measured: 3 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2023
- Study start1 Sep 2019
- Primary completion1 Sep 2025 (estimated)
- Study completion1 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Study design This randomized, double-blind, placebo-controlled, non-inferiority clinical study is actually carried out at the Department of Heart Disease, Centre of Postgraduate Medical Education, Warsaw, Poland. The study will include 390 participants presenting with an episode of AF lasting less than 48 h. All participants must sign an informed consent form. The study protocol was approved by the local ethics committee and is in full compliance with the Declaration of Helsinki.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre of Postgraduate Medical Education
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jarosław Karwowski, Centre of Postgraduate Medical Education
- Investigators
- Jarosław JK Karwowski, PhD, Principal investigator, Centre of Postgraduate Medical Education
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05720572
- Sponsor's protocol ID
- CMKP/85/PB/2019
- Acronym
- AnProAF
- Status last verified
- Feb 2023
- First submitted
- 31 Jan 2023
- Last updated
- 14 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Efficacy and Safety of Antazoline in Comparison to Propafenone in Conversion of Paroxysmal Atrial Fibrillation to Sinus Rhythm - a Single Center, Randomized, Double-blinded Study (the AnProAF Study).
- ClinicalTrials.gov ID
- NCT05720572
- Acronym / sponsor ID
- AnProAF / CMKP/85/PB/2019
- Conditions
- Atrial Fibrillation
- Keywords
- Antazoline, Antiarrhythmic drugs, Pharmacological cardioversion, Atrial fibrillation, Randomized controlled trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 105 participants (estimated)
- Lead sponsor
- Centre of Postgraduate Medical EducationUniversity, hospital or other
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 1 Sep 2025 (estimated)
- Study completion
- 1 Jan 2026 (estimated)
- First posted
- 9 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this randomized, double blind, non-inferiority clinical trial was to compare the clinical efficacy and safety of antazoline with propafenone in the rapid conversion of paroxysmal non-valvular atrial fibrillation to sinus rhythm in patients without heart failure
Detailed description
Background
Atrial fibrillation (AF) is the most common type of arrhythmia, and occurs in approximately 3% of the population over 20 years of age and 9% of those over 80 years of age [1]. Restoration of sinus rhythm (SR) remains an integral part of the treatment for this type of arrhythmia. Early pharmacological (PCV) or electrical cardioversion (ECV) is necessary to improve symptoms, prevent the side effects of the prolonged crisis of arrhythmia, and avoid hospitalization. ECV requires general sedation and does not prevent from immediate AF recurrence. Therefore, the majority of patients are qualified for pharmacological attempts to terminate the arrhythmia. The early PCV of AF to SR may be achieved by administration of Class (Vaughan-Williams) IA, IC, and III antiarrhythmic drugs (AADs): flecainide, ibutilide, dofetilide, propafenone, amiodarone, or novel agent vernakalant. These AADs have limitations such as proarrhythmic side effects in patients with structural heart disease (IC), delayed onset of action (amiodarone), high cost, and low availability (vernakalant) [1].
An efficacious, well-tolerated, less expensive antiarrhythmic drug with rapid onset of action is necessary. Antazoline meslate is an antihistaminic agent with antiarrhythmic quinidine-like properties, which have been documented in 1960s [2,3]. Electrophysiologically, antazoline prolongs action potential duration and lowers its amplitude, prolongs phase-0 duration, reduces phase-4 of resting potential, and reduces excitability of cardiac tissue. Anticholinergic action of this drug leads to transient increase of heart rate, improving atrioventricular conduction and increasing the corrected QT-interval, left atrial refractory period, and inter-atrial conduction time [4-6]. In human healthy volunteers, the terminal elimination half-life of antazoline was 2.29 hours with a mean residence time of 3.45 hours [7]. In clinical practice, the drug can be administered intravenously in boluses of 50-100 mg every 3-5 minutes until successful cardioversion or up to a cumulative dose of 250-350 mg [8].
In Poland, it was registered for intravenous termination of supraventricular arrhythmias. Unfortunately, antazoline is not listed in any of the formal guidelines due to the lack of large randomized trials comparing this drug with other AADs in SR restoration. To the best of our knowledge, only one randomized clinical trial has been published that evaluated the antiarrhythmic effect of antazoline in comparison to placebo [9]. In antazoline group (38 patients), successful conversion of AF to SR was achieved in 72.2%, with a median duration of 16 minutes. Other published observational studies have shown high efficacy of antazoline, ranging between 50% and 80% and a rapid onset of action with cardioversion duration between 7 and 20 minutes [3,8,10-14]. The aim of this randomized, double blind, placebo-controlled, non-inferiority clinical trial is to assess clinical efficacy of antazoline in rapid conversion of atrial fibrillation to sinus rhythm in patients with paroxysmal atrial fibrillation without significant valvular disease or advanced heart failure.
Methods Study objectives The purpose of the study is to assess clinical efficacy of antazoline in rapid conversion of AF to SR in comparison to propafenone in patients with paroxysmal atrial fibrillation without significant valvular disease or advanced heart failure. Due to a presumed lack of statistical power, secondary end points and safety analysis will be considered exploratory.
Study design This randomized, double-blind, placebo-controlled, non-inferiority clinical study is actually carried out at the Department of Heart Disease, Centre of Postgraduate Medical Education, Warsaw, Poland. The study will include 390 participants presenting with an episode of AF lasting less than 48 h. All participants must sign an informed consent form. Approval for the study was obtained from the local ethics committee (nr 85/PB/2019; July 10, 2019).
The study protocol was approved by the local ethics committee and is in full compliance with the Declaration of Helsinki.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Study design This randomized, double-blind, placebo-controlled, non-inferiority clinical study is actually carried out at the Department of Heart Disease, Centre of Postgraduate Medical Education, Warsaw, Poland. The study will include 390 participants presenting with an episode of AF lasting less than 48 h. All participants must sign an informed consent form. The study protocol was approved by the local ethics committee and is in full compliance with the Declaration of Helsinki.
| Arm | Type | Receives |
|---|---|---|
| Antazoline | Experimental | Drug: AntazolineAny 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 3 hours after the first 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. |
| Propafenone | Active comparator | Drug: PropafenoneAny 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 3 hours after the first 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. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Written informed consent for participating in the study and written standard version of informed consent for cardioversion accepted at the Department of Heart Disease, Warsaw, Poland
- Age 18 to 90years
- AF lasting < 48 hours
- Stable cardio-pulmonary state on enrollment
- In case of unclear history of heart failure or suspicion of left ventricle damage echocardiographyis indicated prior to enrollment
Key exclusion criteria (19 listed)
- Lack of written informed consent
- Allergy to antazoline or propafenone
- Intolerance of anatzoline or propafenone
- AF related to significant valvular disease
- Clinically significant heart failure or ejection fraction <50%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AntazolineParticipants assigned to the antazoline group will be administered antazoline in boluses in boluses of 100 mg diluted to 20 cm3 every 10 minutes up to a total dose of 300 mg diluted to 60 cm3 or conversion of AF to SR. Drug administration will also be stopped in case of an adverse event or conversion of AF to a different supraventricular arrhythmia. BP will be measured before every injection. | Drug | Antazoline |
| PropafenonePatients assigned to the propafenone group were administered three 20-cm3 boluses every 10 minutes up to 60 cm3 or conversion of AF to SR. Each of the first two boluses included 70 mg propafenone (total dose 140 mg), and the third bolus contained only 20-cm3 0.9% NaCl. Drug administration will be stopped in case of an adverse event or conversion of AF to a different supraventricular arrhythmia. BP will be measured before every injection. | Drug | Propafenone |
Primary outcome
Conversion of atrial fibrillation (AF) to sinus rhythm (SR)
Time frame: 3 hours
Conversion of AF to SR confirmed in standard 12-lead ECG during the observation period
14 secondary outcomes
Time to conversion of atrial fibrillation to sinus rhythm
Time frame: 3 hours
Serious adverse event defined as every adverse event requiring hospitalization or prolonged observation
Time frame: 3 hours
Disturbances of atrioventricular conduction
Time frame: 3 hours
Hypotension < 90mmHg
Time frame: 3 hours
Pauses > 4s
Time frame: 3 hours
Tachycardia > 180bpm
Time frame: 3 hours
Nausea and/or vomiting
Time frame: 3 hours
Hot flush
Time frame: 3 hours
Drowsiness
Time frame: 3 hours
Headache
Time frame: 3 hours
Bitter/metallic taste
Time frame: 3 hours
Anxiety
Time frame: 3 hours
New complex ventricular arrhythmia
Time frame: 3 hours
Prolongation of QTc in ms (Bazett's formula) in comparison to baseline
Time frame: 3 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2023.
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Atrial Fibrillation (AF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jarosław JK Karwowski, PhD principal investigator
Centre of Postgraduate Medical Education
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Antazoline and Propafenone in people with Atrial Fibrillation, run by Centre of Postgraduate Medical Education at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jarosław JK Karwowski, PhD (+48502913169, karwowski.jarek@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conversion of atrial fibrillation (AF) to sinus rhythm (SR) (time frame: 3 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2023.