Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2, Proof of Concept, Randomized, Placebo-Controlled, Parallel Group Study to Evaluate the Effect of Ranolazine and Dronedarone When Given Alone and in Combination on Atrial Fibrillation Burden in Subjects With Paroxysmal Atrial Fibrillation
Brief Summary: The primary objective of this study is to evaluate the effect of ranolazine and of low-dose dronedarone when given alone and in combination at different dose levels on atrial fibrillation burden (AFB) over 12 weeks of treatment. AFB is defined as the total time a participant is in atrial tachycardia/atrial fibrillation (AT/AF) expressed as a percentage of total recording time.


Options:
A: Inclusion Criteria:

* Adult patients meeting ACC/AHA criteria for paroxysmal atrial fibrillation (episodes typically last no more than 7 days and are self-terminating)
* Eligible for pulmonary vein isolation
* Able to tolerate antiarrhythmic medication

Exclusion Criteria:

* Age \<18
* Persistent or permanent atrial fibrillation (episodes last \>7 days and require cardioversion)
* Antiarrhythmic treatment for indication other than atrial fibrillation
* Contraindication or intolerance to all antiarrhythmic medications
* Primary physician unwilling to withhold antiarrhythmic drugs for duration of the study
* Failure to obtain informed consent
B: Key Inclusion Criteria:

* Males and females aged 18 years and older
* Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* History of PAF documented within the prior 12 months

  - Patients with PAF undergoing cardioversion greater than 4 weeks prior to Screening are eligible
* Implanted (at least 3 months prior to Screening) dual chamber programmable pacemakers with AF detection capabilities
* AFB ≥ 1% and ≤ 70% between the last clinic evaluation and Screening (minimum of 1 month observation period) and AFB ≥ 2% and ≤ 70% during the Run in period
* Sexually active females of childbearing potential must agree to utilize effective methods of contraception during heterosexual intercourse throughout the treatment period and for 14 days following discontinuation of the study medication

Key Exclusion Criteria:

Disease - specific:

* Persistent AF or Permanent AF
* History of atrial flutter or atrial tachycardia without successful ablation
* Other acutely reversible causes of AF, including but not limited to: hyperthyroidism, pericarditis, myocarditis, or pulmonary embolism
* New York Heart Association (NYHA) Class III and IV heart failure or NYHA Class II heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic within 4 weeks prior to Screening.
* Recent history of left ventricular ejection fraction (LVEF) \< 40%
* Myocardial infarction, unstable angina, or coronary artery bypass graft (CABG) surgery within three months prior to Screening or percutaneous coronary intervention (PCI) within 4 weeks prior to Screening
* Clinically significant valvular disease in the opinion of the Investigator
* Stroke within 3 months prior to Screening
* History of serious ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation) within 4 weeks prior to Screening
* Family history of long QT syndrome
* Corrected QT interval (QTc) ≥ 500 msec (Bazett) at Screening ECG if in sinus rhythm (SR). If in AF, evidence of QTc ≥ 500 msec (Bazett) within 4 weeks prior to Screening
* Prior heart transplant
* Cardiac ablation within 4 months prior to Screening, or planned ablation during the course of the study

Concomitant medications/food

* Need for concomitant treatment during the trial, with drugs or products that are strong inhibitors of cytochrome P450 3A (CYP3A), or inducers of CYP3A

  - Such medications should be discontinued 5-half lives prior to the Run-in period
* Use of grapefruit juice or Seville orange juice during the study
* Use of Class I and Class III antiarrhythmic drugs other than amiodarone within 5-half lives prior to the Run-in period
* Use of amiodarone within 3 months prior to Screening
* Use of drugs that prolong the QT interval
* Previous use of ranolazine or dronedarone within 2 months prior to screening
* Prior use of ranolazine or dronedarone which was discontinued for safety or tolerability
* Use of dabigatran during the study
* Use of digitalis preparations (eg, digoxin) during the study
* Use of a greater than 1000 mg total daily dose of metformin during the study

Laboratory tests:

* Hypokalemia (serum potassium \< 3.5 mEq/L) at Screening that cannot be corrected to a level of potassium ≥ 3.5 mEq/L prior to randomization
* Moderate and severe hepatic impairment (ie, Child-Pugh Class B and C), abnormal liver function test defined as alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin \> 2 x upper limit of normal (ULN) at Screening
* Severe renal impairment defined as creatinine clearance ≤ 30 mL/min at Screening

Others:

* Females who are pregnant or are breastfeeding
* In the judgment of the Investigator, any clinically-significant ongoing medical condition that might jeopardize the individual's safety or interfere with the study, including participation in another clinical trial within the previous 30 days using a therapeutic modality which could have potential residual effects that might confound the results of this study
* Any device-related technical issue which in the judgment of the investigator would disrupt adequate data collection or interpretation (eg, anticipated pulse generator change or lead revision)

Note: Other protocol defined Inclusion/Exclusion criteria may apply.
C: Inclusion Criteria:

* Patients with persistent atrial fibrillation (more than 7 days, or less than 7 days needing pharmacologic or electric cardioversion)

Exclusion Criteria:

* Hypo or hyperthyroidism
* Persistent atrial fibrillation lasting more than 1 year or non-defined duration
* Hypertrophic myocardiopathy
* Implantable defibrillation or pacemaker implanted
* Moderate or severe mitral valve disease or mitral prosthetic valve
* Ejection fraction less than 30%
* Left atrial anteroposterior diameter more than 50 mm.
* Previous atrial fibrillation ablation
* Contraindication to anticoagulation
* Left atrium thrombus
* Current infective disease or sepsis
* Pregnant women
* Current unstable angor
* Acute myocardial infarction in last 3 months
* Atrial fibrillation secondary to ionic disturbance, thyroids disease or secondary to any other reversible or non cardiovascular disease
* Reduced expectancy of life (less than 12 months)
* Patient participating in another clinical study that investigates a drug or device
* Psychologically unstable patient or denies to give informed consent
* Any cause that contraindicate ablation procedure or antiarrhythmic drug
D: Inclusion Criteria:

* Subject is ≥ 18 years of age
* Subject must be diagnosed with Persistent and/or Longstanding Persistent Atrial fibrillation as classified by the HRS Guidelines 8 \[0\]
* Subject must be selected as a candidate to undergo the Cox- Maze procedure for ablation of atrial fibrillation
* The Cox Maze procedure may be done as a stand alone procedure or combined with other cardiac surgical procedures either via a median sternotomy or a right thoracotomy:
* Subject has a Left Ventricular Ejection Fraction (LVEF) ≥ 30%
* Subject would normally be prescribed Amiodarone as an anti arrhythmic medication post surgical ablation
* Subject is able and willing to provide written informed consent and HIPAA authorization
* Subject is able and willing to comply with all study requirements including attending all follow-up visits as deemed necessary by personal physician (cardiologist)
* Subject has a life expectancy of at least one year

Exclusion Criteria:

* Subject has undergone previous attempts at surgical Maze procedure or other AF operation, including surgical or catheter ablation Subject has an accessory pathways disorder (e.g. Wolff-Parkinson-White syndrome)
* Subject is in Class IV NYHA
* Subject has had a documented MI within 6 weeks prior to study enrollment
* Subject needs emergent cardiac surgery (i.e. cardiogenic shock)
* Subject has known carotid artery stenosis greater than 80%
* Subject has a current diagnosis of active systemic infection
* Subject is pregnant, planning to become pregnant within 12-14 months, or lactating
* Subject requires preoperative intra-aortic balloon pump or intravenous inotropes
* Subject has renal failure requiring dialysis
* Subject is diagnosed with hepatic failure
* Subject is on anti-arrhythmic drug therapy for the treatment of a ventricular arrhythmia
* Subject has a known connective tissue disorder
* Subject is incarcerated
* Subject has previous or current therapy that could compromise tissue integrity including thoracic radiation, chemotherapy, long-term oral or injected steroids
* Subject is an intravenous drug and/or alcohol abuser
* Subject is participating in concomitant research studies of investigational products ( e.g. Appendage closure devices, atrial septal defect patches)

Answer: B