Comparison of Effectiveness of Ranolazine Plus Metoprolol Combination vs. FlecainidE pluS Metoprolol Combination in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation (PRESERVE-SR)
Primary Purpose
Atrial Fibrillation, Recurrence
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Ranolazine plus Metoprolol Combination
FlecainidE pluS Metoprolol Combination
Sponsored by
About this trial
This is an interventional treatment trial for Atrial Fibrillation
Eligibility Criteria
Inclusion Criteria:
- patients with AF
- recently converted to sinus rhythm (>24hrs and < 7 days)
- admitted in the 3rd University Cardiology Clinic of Ippokrateion Hospital
- eligible to participate in the study and follow the study procedures
- signed informed consent
Exclusion Criteria:
- use of IC antiarrhythmic agents or
- Sotalol during the last 48 hours,
- chronic use of oral or intravenous Amiodarone for the last 48 hours,
- recent acute coronary syndrome,
- heart failure New York Heart Association class III or IV,
- severe left ventricular dysfunction with left ventricular ejection fraction <40%,
- atrioventricular conduction disorders (atrioventricular block,
- complete left bundle branch block and bi-fascicular block),
- heart rate < 50 bpm,
- sick sinus syndrome,
- thyroid dysfunction and severe pulmonary, renal, or
- liver disease
- - not eligible to participate in the study and follow the study procedures
- no signed informed consent
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Ranolazine plus Metoprolol Combination
FlecainidE pluS Metoprolol Combination
Arm Description
Ranolazine plus Metoprolol Combination in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation
FlecainidE pluS Metoprolol Combination in in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation
Outcomes
Primary Outcome Measures
Number of 1-year-recurrences
efficacy and safety of the combination of RN and Metoprolol vs. the combination of Flecainide and Metoprolol in preventing AF recurrences during a 1-year follow-up period in patients with AF of longer than 24-hour duration who were cardioverted to sinus rhythm either pharmacologically or electrically
Secondary Outcome Measures
Number of 48-hours-recurrences
Time to the first documented AF recurrence excluding patients with recurrences in the first 48 hours
Full Information
NCT ID
NCT03162120
First Posted
May 17, 2017
Last Updated
May 10, 2019
Sponsor
Elpen Pharmaceutical Co. Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03162120
Brief Title
Comparison of Effectiveness of Ranolazine Plus Metoprolol Combination vs. FlecainidE pluS Metoprolol Combination in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation
Acronym
PRESERVE-SR
Official Title
A Single Site, Interventional, Comparative Study to Evaluate the Safety and Efficacy of Ranolazine Plus Metoprolol Combination vs. FlecainidE pluS Metoprolol Combination in ATrial Fibrillation Recurrences
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Withdrawn
Why Stopped
new study type, it will be re-organiZed as an Investigator Initiated Study (IIS)
Study Start Date
September 1, 2018 (Anticipated)
Primary Completion Date
December 1, 2018 (Anticipated)
Study Completion Date
December 1, 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Elpen Pharmaceutical Co. Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice with a prevalence reaching 5% in patients older than 65 years and an incidence that increases progressively with age.1 According to the most recent guidelines, class Ic anti-arrhythmic drugs are considered the first line treatment in patients without significant structural heart disease. Flecainide is effective in preventing AF recurrences in 31-61% of cases according to different studies.2-5 A recent study showed that the combination of Flecainide and Metoprolol improves effective rhythm control in patients with persistent symptomatic AF compared to Flecainide or Metoprolol alone.6 In contrast, the combination of Flecainide and Metoprolol conferred no significant benefit over Flecainide alone in patients with paroxysmal AF. This suggests different underlying mechanisms for paroxysmal and persistent AF. Pulmonary veins are likely the main focus triggering paroxysmal AF while in persistent AF the role of pulmonary veins is less important.
Detailed Description
Ranolazine (RN) is a novel antianginal agent with increasingly appreciated antiarrhythmic properties that can suppress ventricular and supraventricular arrhythmias including AF. The antiarrhythmic actions of RN are mainly attributed to its ability to block INa, INaL, and the rapidly activating delayed rectifier potassium current (IKr).7 In experimental studies, RN proved very effective in suppressing late phase 3 early afterdepolarization and delayed afterdepolarization mediated triggered activity in pulmonary vein sleeves.8 RN was shown very effective in suppressing persistent, vagally mediated AF in animal models.9 Clinical evidence of an AF-suppressing effect of RN comes mainly from small caliber studies. Murdock et al, reported a high conversion rate (72%) after administration of 2,000 mg of RN (in a "pill-in-the-pocket" fashion) in patients with short lasting (<48 hours) new onset paroxysmal AF.10 Our group demonstrated both the superior efficacy and the accelerated action of the combined therapy of Amiodarone with RN compared to Amiodarone alone in patients with paroxysmal AF. Notably, the efficacy benefit of this combination was more pronounced in patients with dilated left atria which is also more likely to occur in cases of persistent AF.11, 12 In a prospective, randomized, double-blind, placebo-control phase II study, different doses of RN were tested in the prevention of AF recurrence after successful electrical cardioversion. Despite the fact that the study did not reach its primary end-point since none of the individual doses of RN significantly delayed the time to first AF recurrence as compared with placebo, an antiarrhythmic efficacy for the two higher doses of RN (500 and 750mg bd) was strongly suggested. The same study confirmed the safety of RN with no evidence for proarrhythmia.13 Notably, beta-blockers were used in less than 50% of patients studied in this study.
Although the efficacy of beta-blockers in the maintenance of sinus rhythm is low, the addition of a beta-blocker to an antiarrhythmic agent that exerts its action by inhibiting inward Na+ current like RN and Flecainide may represent an interesting approach in preventing AF relapse. Various laboratory studies have demonstrated that inward Na+ current could be modulated by beta-adrenergic receptors in a variety of cell lines.14, 15 In this context, the beta-blocking activity of Amiodarone or Dronedarone may account for the successful combination with RN in suppressing AF in either experimental or clinical studies.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Recurrence
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ranolazine plus Metoprolol Combination
Arm Type
Active Comparator
Arm Description
Ranolazine plus Metoprolol Combination in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation
Arm Title
FlecainidE pluS Metoprolol Combination
Arm Type
Active Comparator
Arm Description
FlecainidE pluS Metoprolol Combination in in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation
Intervention Type
Drug
Intervention Name(s)
Ranolazine plus Metoprolol Combination
Other Intervention Name(s)
RM group
Intervention Description
Ranolazine plus Metoprolol Combination in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation
Intervention Type
Drug
Intervention Name(s)
FlecainidE pluS Metoprolol Combination
Other Intervention Name(s)
FM group
Intervention Description
FlecainidE pluS Metoprolol Combination in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation
Primary Outcome Measure Information:
Title
Number of 1-year-recurrences
Description
efficacy and safety of the combination of RN and Metoprolol vs. the combination of Flecainide and Metoprolol in preventing AF recurrences during a 1-year follow-up period in patients with AF of longer than 24-hour duration who were cardioverted to sinus rhythm either pharmacologically or electrically
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Number of 48-hours-recurrences
Description
Time to the first documented AF recurrence excluding patients with recurrences in the first 48 hours
Time Frame
48 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
patients with AF
recently converted to sinus rhythm (>24hrs and < 7 days)
admitted in the 3rd University Cardiology Clinic of Ippokrateion Hospital
eligible to participate in the study and follow the study procedures
signed informed consent
Exclusion Criteria:
use of IC antiarrhythmic agents or
Sotalol during the last 48 hours,
chronic use of oral or intravenous Amiodarone for the last 48 hours,
recent acute coronary syndrome,
heart failure New York Heart Association class III or IV,
severe left ventricular dysfunction with left ventricular ejection fraction <40%,
atrioventricular conduction disorders (atrioventricular block,
complete left bundle branch block and bi-fascicular block),
heart rate < 50 bpm,
sick sinus syndrome,
thyroid dysfunction and severe pulmonary, renal, or
liver disease
- not eligible to participate in the study and follow the study procedures
no signed informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vasilios Vasilikos, MD
Organizational Affiliation
3rd University Cardiology Clinic of Ippokrateion Hospital, Thessaloniki, Greece
Official's Role
Study Chair
12. IPD Sharing Statement
Plan to Share IPD
No
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Learn more about this trial
Comparison of Effectiveness of Ranolazine Plus Metoprolol Combination vs. FlecainidE pluS Metoprolol Combination in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation
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