Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation, Ranolazine
Brief summary
The investigators hypothesize that ranolazine would decrease the incidence of recurrence of Atrial Fibrillation (AF) after electrical cardioversion of persistent AF. Patients with persistent AF who are candidates for electrical cardioversion will be randomized to either placebo or ranolazine after successful electrical cardioversion.
Detailed description
Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia and is associated with increased cardiovascular morbidity and mortality. Although a rhythm control strategy offers no survival benefit over a rate control strategy, elective electrical cardioversion is still recommended in patients without hemodynamic instability for symptomatic relief. However, recurrences are frequent after cardioversion and antiarrhythmic medications are required to maintain sinus rhythm. Nonetheless, the use of antiarrhythmic medications is problematic because of the risk of serious potential adverse effects, including drug-induced ventricular arrhythmias. Ranolazine is a novel antianginal agent, which inhibits the late inward sodium current and produces antiischemic effects without reducing heart rate or blood pressure. Additionally, recent preclinical as well as preliminary clinical data suggest that ranolazine exhibits distinct antiarrhythmic properties. However, there is no controlled data for the use of ranolazine to prevent recurrence of AF after electrical cardioversion of persistent AF. The investigators hypothesize that ranolazine would decrease the incidence of recurrence of AF after electrical cardioversion of persistent AF. Patients with persistent AF who are candidates for electrical cardioversion will be randomized to either placebo or ranolazine after successful electrical cardioversion. They will be followed at 2 weeks, 1, 3 and 6 months for clinical evaluation and electrocardiography for the detection of recurrence of AF.
Interventions
DRUGRanolazine
Patients will be started on ranolazine 500mg twice daily. The first dose will be administered the day of cardioversion. The dose will be doubled after 2 weeks to 1000mg twice daily as tolerated for a total of six months.
DRUGMatching placebo
Patients will be started on a matching placebo twice daily. The first dose will be administered the day of cardioversion and continued for a total of six months.
Sponsors
Gilead Sciences
University of Oklahoma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female with persistent atrial fibrillation, aged 21 or older * Duration of atrial fibrillation less than one year * The patient does not have any contraindications for anticoagulation * The patient is willing to participate in the study for a total of 6 months with 3 outpatient office visits * The patient has provided written informed consent during the screening visit to any test or procedure being performed, or medication being changed, for this study. * The patient has no clinically significant abnormal clinical laboratory values, which in the investigator's opinion precludes the patient from safely participating in the study.
Exclusion criteria
* Any contraindication for anticoagulation * New York Heart Association class IV heart failure * Currently taking anti-arrhythmic drugs * Chronic kidney disease (serum creatinine less than 2.5mg/dL) or severe liver dysfunction * Pregnancy/nursing * Prolonged QT interval (\>500ms) * Taking other medications known to prolong the QT interval * Taking other medications known to affect the metabolism of ranolazine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome - Number of Participants With Atrial Fibrillation | 6 months | To determine if ranolazine is effective in decreasing recurrences of AF in patients with persistent AF successfully treated with electrical cardioversion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine Patients will be started on ranolazine 500mg twice daily. The dose will be doubled after 2 weeks to 1000mg twice daily as tolerated.
Ranolazine: Patients will be started on ranolazine 500mg twice daily. The first dose will be administered the day of cardioversion. The dose will be doubled after 2 weeks to 1000mg twice daily as tolerated for a total of six months. | 5 |
| Placebo Patients will be started on a matching placebo twice daily. The first dose will be administered the day of cardioversion.
Matching placebo: Patients will be started on a matching placebo twice daily. The first dose will be administered the day of cardioversion and continued for a total of six months. | 5 |
| Total | 10 |
Baseline characteristics
| Characteristic | Ranolazine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 |
Outcome results
Primary
Primary Outcome - Number of Participants With Atrial Fibrillation
To determine if ranolazine is effective in decreasing recurrences of AF in patients with persistent AF successfully treated with electrical cardioversion.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranolazine | Primary Outcome - Number of Participants With Atrial Fibrillation | 3 participants |
| Placebo | Primary Outcome - Number of Participants With Atrial Fibrillation | 3 participants |