Study of Ranolazine in the Treatment of Pulmonary Hypertension Associated With Diastolic Left Ventricular Dysfunction
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|ClinicalTrials.gov Identifier: NCT02133352|
Recruitment Status : Completed
First Posted : May 8, 2014
Results First Posted : May 17, 2017
Last Update Posted : May 17, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Hypertension Diastolic Left Ventricular Dysfunction||Drug: Ranolazine||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Proof of Concept Study of Ranolazine in the Treatment of Pulmonary Hypertension Associated With Diastolic Left Ventricular Dysfunction|
|Study Start Date :||July 2011|
|Actual Primary Completion Date :||May 2013|
|Actual Study Completion Date :||May 2014|
Ranolazine- initiated at 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.
Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Other Name: Ranexa
- Percent Change in mPAP, PAOP and Pulmonary Vascular Resistance (PVR) [ Time Frame: 180 days ]
Assess the percent change in mPAP, PAOP and pulmonary vascular resistance (PVR) by RHC.
Additional RHC completed at optional follow up for patients remaining on ranolazine upon completion of 180 day period.
- Percent Change in Other Hemodynamic Parameters [ Time Frame: 180 days ]
Assess % change in other hemodynamic parameters, by RHC, from baseline afeter 180 days of ranolazine.
Right atrial pressure (RAP) Systolic pulmonary artery pressure (SPAP) Diastolic pulmonary artery pressure (DPAP) Cardiac output (CO) Cardiac index (CI)
- 6 Minute Walk Test (6MWT) [ Time Frame: 180 days ]Assess the change from baseline in 6 minute walk test (6MWT) after 180 days of twice daily ranolazine Optional follow up for some patients also includes 6MWT.
- Change in Cardiac Size and Function [ Time Frame: 180 days ]
Assess changes from baseline in measurements of cardiac size and function obtained by MRI after 180 days of twice daily ranolazine.
An additional MRI may be completed at optional follow up visit for patients continuing on ranolazine following completion of the 180 day treatment period.
- Change in Echocardiogram Parameters (LVEF) [ Time Frame: 180 days ]
To assess the changes from baseline in echocardiographic parameters (left ventricular geometry and function, LVEF, evidence of diastolic dysfunction, SPAP, right ventricular geometry and function, degree of tricuspid regurgitation) after 180 days of twice daily ranolazine.
An additional echo may be completed at optional follow up visit for patients continuing on ranolazine following completion of the 180 day treatment period.
- Change in BNP Cardiac Biomarker [ Time Frame: 180 days ]
Assess the change from baseline in BNP cardiac biomarkers after 180 days of twice daily ranolazine.
Cardiac biomarkers may be completed at optional follow up visit for patients continuing on ranolazine following completion of the 180 day treatment period.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02133352
|United States, Massachusetts|
|Boston University Medical Center|
|Boston, Massachusetts, United States, 02118|
|Principal Investigator:||Harrison Farber, MD||Boston University|