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Cardiovascular Medicine - Active Clinical Trials
HESTIA


Primary Investigator: Greg Flaker, MD

Study Coordinator: Kathy Belew, CNS-BC

Status: A
ctive - open to enrollment

Study Title: A placebo-controlled, double-blind, randomized, multi-center study to assess the effects of Dronedarone 400 mg BID for 12 weeks on atrial fibrillation (AF) burden in subjects with permanent pacemakers

Purpose: T
he primary objective of this study is to evaluate the effects of dronedarone on AF burden based on electrogram (EGM) data in subjects with a permanent pacemaker. AF burden is defined as the percent of time in which a subject is in AF.

Inclusions:
1. Paroxysmal AF or AFL documented by evidence of AF/AFL and sinus rhythm within the prior six months and with a minimum AF burden and pacemaker requirements as follows:
•-       A programmable dual chamber pacemaker with lead placement no less than three months before screening, a minimum capability of storing three months or more of EGM data, and an expected remaining battery life of one year or more.
•-       AF burden ≥ 1% on pacemaker EGM interrogation at the initial (screening) visit (Week four/Visit one) with at least one episode of AF within the prior 28 days. Must include at least 28 days of continuous data retrieved from the pacemaker interrogation report.

Exclusions:
1.   Unlikely to comply with the protocol requirements (e.g., illiterate, uncooperative, unable to return for follow-up visit, unlikely to complete the study).
2.   Less than 21 years of age.
3.   AF burden of < 1% during the screening period, as assessed at Day one/Visit two (must include 28 [± 3] days of continuous data retrieved from the pacemaker interrogation report).
4.   Does not have at least one of the following cardiovascular (CV) risk factors:
      • Age ≥ 70 years at start of screening.
     
• Hypertension (taking antihypertensive drugs of at least two different classes).
     
• Diabetes mellitus.
      
• Prior CV accident (stroke or transient ischemic attack) or systemic embolism.
     
• Left atrium diameter ≥ 50 mm by M-mode or 2D echocardiography within the prior 12 months.
     
• Left ventricular ejection fraction ≤0.40 by M-mode or 2D echocardiography, cardiac catheterization, or nuclear cardiac imaging study within the prior 12 months.
5.    Permanent AF (defined as continuous AF for six months or longer).
6.    Evidence of persistent AF during screening period (defined as continuous AF activity lasting longer than seven days as demonstrated on the EGM report prior to randomization or requiring electrical cardioversion or overdrive pacing for termination).
7.    Electrical cardioversion (or overdrive pacing) within four weeks prior to screening.
8.    Cardiac ablation procedure within tjree months prior to screening.
9.    Evidence at screening of uncorrected atrial undersensing or oversensing documented in routine pacemaker evaluation or:
      
• Sensed P wave in SR < 1 mV
      
• Subjects requiring atrial sensitivity to be set > 0.75 mV
10.  Subjects for whom the pacemaker programming requirements for this study are not clinically feasible, are contraindicated, or could pose risk.
11.  Ongoing potentially dangerous symptoms when in AF/AFL such as angina pectoris, transient ischemic attacks, stroke, or syncope as judged by the Investigator.
12.  NYHA Class IV heart failure or NYHA Class II or Class III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic within four weeks prior to screening.
13.  Evidence of clinical instability including hypotension, unstable angina and hemodynamically significant obstructive valvular disease, hemodynamically significant obstructive cardiomyopathy, a cardiac operation, or revascularization procedure within four weeks prior to screening.
14.  Noncardiovascular illness or disorder that could preclude participation or severely limit survival including cancer with metastasis and organ transplantation requiring immune suppression.
15.  Planned noncardiac or cardiac surgery or procedures including surgery for valvular heart disease, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), cardiac transplantation or electrical cardioversion for AF/AFL.
16.  Need for concomitant medication that is prohibited in this trial and would preclude the use of Investigational Product during the planned study period, including the following:
      
• Antiarrhythmics (e.g., amiodarone, flecainide, propafenone, quinidine, disopyramide, dofetilide, sotalol).
      
• Drugs or products that are strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, ritonavir, and grapefruit juice).
      
• CYP3A inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin, and St. John's wort).
18. Chronic use of amiodarone within the four weeks prior to screening.
19. Use of Class I or Class III antiarrhythmics (other than amiodarone) within five-half lives prior to screening.
20. Use of St John's wort, grapefruit juice, or drugs that prolong the QT interval and might increase the risk of torsade de pointes (e.g., phenothiazine anti-psychotics, tricyclic antidepressants, certain oral    macrolide antibiotics, and Class I and III antiarrhythmics).
21. Inability or unwillingness to comply with oral anticoagulation therapy, if indicated.
22. QTc Bazett interval ≥ 500 msec based on screening (if in sinus rhythm).
23. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) at screening.
24. Uncorrected hypokalemia (serum potassium < 3.5 mEq/L).
25. Severe hepatic impairment (i.e., Child-Pugh Class C), abnormal liver function test (LFT) defined as alanine aminotransferase [ALT], aspartate aminotransferase [AST], or bilirubin > 2 X upper limit of       normal [ULN] or renal impairment defined as serum creatinine >2.0 mg/dL at screening.
26. Uncontrolled diabetes mellitus (documented history of HbA1c >10% at the most recent assessment prior to screening).
27. Pregnant women or women of childbearing potential not on adequate birth control (urine pregnancy test must be negative): only postmenopausal women, sterile women, or women with a highly effective       method of contraception (oral contraception or intra-uterine device [IUD]) can be randomized.
28. Breastfeeding women.
29. Previous (within two months prior to screening) or current participation in another clinical trial with an investigational drug (under development) or with an investigational device.

Actions:
1.    Determine if patient fits major study criteria.
2.    Determine if patient is interested in joining a clinical trial.
3.    Call Kathy Belew (beeper 573-499-8063) and/or on-call research nurse (on-call beeper 573-499-8084) or Dr. Flaker to complete screening of patient.




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