Effect of Ranolazine in Heart Failure Patients

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 120

Inclusion Criteria

1.Male or female between the ages of 40 to 85 years, inclusive
2.Heart failure with preserved EF defined by the following:
a.Signs or symptoms of HF (previous documented hospitalization for HF, decompensation in the last 12 months, or exertional dyspnea or fatigue, New York Heart Association [NYHA] Class II-IV with or without clinical signs of HF)
b.LVEF > 45% measured by echocardiogram
c.NT-ProBNP > 200 pg/ml or BNP > 80 pg/ml
d.Evidence of LV diastolic dysfunction or increased LV filling pressure documented in the last month and defined by the following:
?LV end diastolic pressure > 16 mmHg
?or E/E? > 15 (septal annular velocity)
?or E/E? between 8 and 15 and at least one of the following:
?Plasma brain natriuretic peptide (BNP) > 150 pg/ ml or plasma N terminal pro b-type natriuretic peptide (NT proBNP) > 450 pg/ml
?Ratio of early (E) to late (A) mitral valve flow velocity (E/A) < 0.5 and mitral flow deceleration time (DT E) > 280 ms
?LV atrial area > 25 cm² (apical 4 chamber)
?LV posterior wall thickness > 12 mm
e.Sinus rhythm
3.Written informed consent
4.6MWT distance ? 450 meters and ? 100 meters at screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

1.Unstable situation for acute acute coronary syndrome, or worsening angina in the last 3 months
2. Unstable situation for acute heart failure in the last month
3.Poor echogenicity
4.Significant chronic lung disease (e.g., chronic obstructive pulmonary disease, asthma), prior hospitalization for acute exacerbation, home oxygen use, chronic inhaled or systemic steroid therapy
5.Documented hypertrophic or restrictive cardiomyopathy
6.Body mass index (BMI) ? 30 kg/m2
7.Tricuspid Rigurgitation Max Velocity > 4m/s
8.Previous Heart Failure hospitalization or decompensation, with documented LV Systolic Dysfunction (LVEF ? 45%)
9.Sustained atrial fibrillation or flutter in the previous 3 months
10.Change in cardiovascular medication during the last 4 weeks
11.Change in diuretic medication during the last 2 weeks
12.Revascularization within the last 3 months
13.Second- or third-degree atrioventricular (AV) block
14.Severe and uncontrolled hypertension stage 3 (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg)
15.Significant valvular disease: moderate or severe mitral or aortic valve disease
16.Severe renal impairment (creatinine clearance < 30 ml/min)
17.Moderate or severe hepatic impairment (Child-Pugh Class A or Class B)
18.Previous cardiac surgery
19.Inability to perform the 6MWT
20.6MWT distance > 450 meters or < 100 meters at screening
21.Screening and baseline 6-minute walk distance (6MWD) with >10% variability
22.Stroke within the last 3 months
23.Implantable pacemaker for chronotropic incompetence, cardioverter defibrillator, or LV assist device
24.Prior heart transplantation
25.Current treatment with potent inhibitors of CYP3A, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir
26.Current treatment with CYP3A inducers, such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John?s wort
27.Concomitant administration of Class Ia (e.g., quinidine) or Class III (e.g., dofetilide, sotalol) antiarrhythmics other than amiodarone
28.Use of greater than 1000mg daily dose of metformin during the study
29.Use of over 20 mg daily dose of simvastatin
30.Prior treatment with ranolazine
31.Hypersensitivity to the active substance or to any of the excipients
32.Participation in another trial of an investigational drug or device within 30 days prior to screening
33.Pregnant or breast-feeding
34.Severe psychiatric disorders/neurological disorders
35.Abuse of alcohol, analgesics, or psychotropic drugs
36.Disabling or terminal illness
37.Inability or unwillingness, in the Investigator?s opinion, to follow study procedures

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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