Study of Ranolazine in the Treatment of Pulmonary Hypertension Associated With Diastolic Left Ventricular Dysfunction
Condition: Pulmonary Hypertension; Diastolic Left Ventricular Dysfunction
MeSH terms: Hypertension, Pulmonary; Hypertension; Ventricular Dysfunction; Ventricular Dysfunction, Left
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      This single center, prospective, open-label trial to assess the safety and efficacy of
      ranolazine in subjects with pulmonary hypertension associated with left ventricular diastolic
      dysfunction includes a screening period, 6 month treatment period and a follow up period.
      Eligible subjects who provide informed consent and who meet all inclusion/exclusion criteria
      will be enrolled in this study. All subjects will receive active study drug. There is no
      placebo group or use of control subjects. Treating will begin with 500mg twice daily and
      increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for
      the remainder of the Treatment Period. Ranolazine will be limited to 500 mg BID in patients
      taking moderate inhibitors of CYP3A, including diltiazem, verapamil, aprepitant,
      erythromycin, fluconazole, grapefruit juice or grapefruit-containing products. During the
      Treatment Period subjects will be provided bottles of study medication to take home.
      Throughout the Treatment Period, subjects will return to the clinic for safety and/or
      efficacy assessments as well as resupply of Study Medication. Once the Treatment Period is
      complete, subjects will return to the clinic for a Follow-Up visit 14 days after the last
      dose of study medication, for a final safety assessment. Other therapies or possibly
      extension of the ranolazine treatment may be considered after completion of the Treatment
      Period at the discretion of the Investigator and will be recorded at the follow-up visit.
      Subjects who continue taking ranolazine (as part of there clinical care), will be asked to
      return for a 1 year follow up visit for safety and efficacy assessments.

      As part of Amendment 2 (submitted November 2013), subjects who continue on ranolazine after
      the 6 month treatment period (as part of their clinical care) will be asked to return for
      further follow-up testing to better assess the safety and efficacy of the drug. The visit can
      be conducted once the patient has been on drug for a total of one year or greater (including
      the 6 month treatment period). This would replace the 1 Year follow-up visit for subjects who
      have not yet completed the visit and will be an additional visit for those subjects who have.

      Subjects can opt to continue on ranolazine regardless of if they agree to complete the Post
      Treatment Follow up visit. They do not have to continue with the study after the treatment
      phase has been completed in order to stay on ranolazine. The PI and study personnel will
      complete the required forms for the Ranexa Connect application if patient wishes to stay on
      drug. The Ranexa Connect Program assists patients in obtaining insurance coverage of
      ranolazine and financial assistance if needed.

      This is a 6 month, single center, prospective, open-label trial. All subjects will be
      receiving active treatment, ranolazine at doses approved by the FDA. Subjects will begin
      treatment at 500mg twice daily and increase to 1000mg twice daily as tolerated after 2 weeks.
      Subjects will take study drug twice daily with or without food. Ranolazine will be limited in
      subjects taking CYP3A including diltiazem, verapamil, arprepitant, erythromycin, fluconazole,
      grapefruit juice or grapefruit juice containing products. The study will consist of 3
      periods: a screening period, a treatment period, and a follow-up period.

      Subjects will be asked to come to the study center for 9-10 visits over the course of 6
      months. Other therapies or possibly extension of the ranolazine treatment may be considered
      after completion of the treatment period at the discretion of the Investigator at the follow
      up visit. Subjects who continue on ranolazine after completion of the treatment period of the
      study will be asked to return for follow up testing.
    

Intervention name(s): Ranolazine
Intervention type(s): Drug
Intervention description(s): Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Other intervention name(s): Ranexa
Intervention MeSH terms: Ranolazine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: pulmonary hypertension; diastolic dyfunction