Study of Ranolazine in the Treatment of Pulmonary Hypertension Associated With Diastolic Left Ventricular Dysfunction

• Status: Completed
• Trial end date: 2014-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a single center, open-label trial designed to assess the safety and efficacy of ranolazine (Ranexa) in patients with pulmonary hypertension associated with left ventricular diastolic dysfunction. All patients will receive active drug. The study includes a screening period, 6 month treatment period and a follow up period. Eligible patients who provide informed consent and who meet all inclusion/exclusion criteria will be enrolled in this study.

There is neither proven therapy for patients with diastolic dysfunction-associated pulmonary hypertension nor for patients with diastolic dysfunction alone. Ranolazine, an inhibitor of cardiac repolarization (sodium channels), could represent a new and effective treatment of this entity.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Boston University; Harrison Farber
• Collaborator: Gilead Sciences
• Treatments: Ranolazine

Criteria

Inclusion Criteria:

• Written consent prior to any study procedure

• Men or women, ages 18 to 75 years

• Suspicion of Pulmonary Hypertension by echo (RVSP ≥ 50mmHg) or diagnosis of Pulmonary Hypertension by cardiac cath (mPAP ≥25 mmHg at rest)

• LVEF ≥50%, (by ECHO, radionuclide imaging, or cardiac cath)

• 6MWT distance ≥150m and ≤450m at both time points within the Screening Period

• NYHA/WHO functional class II-III

• RHC measurements on Study Day 1: 1) mean pulmonary artery pressure (MPAP) ≥25 mmHg; 2) pulmonary artery occlusion pressure (PAOP) ≥18 mmHg and ≤30 mmHg; 3) pulmonary artery diastolic pressure (PADP) - PAOP ≤10 mmHg

Exclusion Criteria:

• Presence or history of any of the following cardiovascular co-morbidities or conditions: Hypotension at Screening (defined as a resting SBP≤90mmHg). Hypertension at Screening (defined as resting SBP ≥200mmHg), Unstable cardiovascular disease including paroxysmal atrial fibrillation or unstable angina, Amyloidosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis, History of myocardial infarction, coronary artery bypass graft surgery, or percutaneous cardiac intervention, Significant valvular heart disease, Cerebrovascular accident or transient ischemic attack

• Exercise tolerance limited by non-cardiac causes (exercise-induced asthma, malignancy, obesity, musculoskeletal disorder).

• Clinically significant psychiatric, addictive (DSM-IV criteria), neurologic disease or condition that would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the protocol

• Any other condition or co-morbidity that, in the opinion of the Investigator, would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the protocol

• Clinically significant laboratory abnormalities, including: Positive Hep B surface antigen or Hep C antibody, Positive HIV test within one year of Study Day 1, Serum alanine aminotransferase (ALT) ≥ 2.0 x ULN, Total bilirubin ≥ 1.2 x ULN (unless evidence of Gilbert's syndrome). Serum creatinine ≥ 2.5mg/dL (or calculated creatinine clearance less than or equal to 30mL/min). Hemoglobin less than or equal to 10g/dL (subject may qualify for the study following diagnosis and treatment of anemia, if the anemia is due to iron and/or vitamin deficiency).

Patients with moderate or severe hepatic impairment (Child-Pugh Classes B or C) or requiring hemidialysis.

• Subject has received any other investigational medication within the 30 days prior to Screening

• Prior treatment with ranolazine

• Pregnancy or lactation

• Women of childbearing potential and men without vasectomies who are not using barrier method of contraception

• Subject has the presence, or history, of malignancy that required significant medical intervention within the preceding 3 months and/or is likely to result in death within the next 2 years (exception of basal cell, non-metastatic squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix)

• Treatment for pulmonary hypertension with epoprostenol (Flolan), treprostinil (Remodulin), iloprost (Ventavis), bosentan (Tracleer), ambrisentan (Letairis), sildenafil (Revatio), tadalafil (Adcirca). The use of sildenafil, tadalafil, or vardenafil is prohibited for any reason within 7 days of hemodynamic assessments on Days 1 and 180).

• Patients with QTc > 500 msec at baseline

• Treatment with potent CYP3A inhibitors, including ketoconazole, itraconazonle, clarithromycin, nefazodone, nelfinavir, indinavir, & saquinavir

• Treatment with CYP3A inducers, including rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, and St. John's wort.