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

NCT02133352 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 30217
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pulmonary Hypertension; Diastolic Left Ventricular Dysfunction

Keywords

pulmonary hypertension; diastolic dyfunction

Outcome Measures

Primary Outcomes (1)

• Percent Change in mPAP, PAOP and Pulmonary Vascular Resistance (PVR)

  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.

  180 days

Secondary Outcomes (5)

• Percent Change in Other Hemodynamic Parameters

  180 days

• 6 Minute Walk Test (6MWT)

  180 days

• Change in Cardiac Size and Function

  180 days

• Change in Echocardiogram Parameters (LVEF)

  180 days

• Change in BNP Cardiac Biomarker

  180 days

Study Arms (1)

Ranolazine

EXPERIMENTAL

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.

Drug: Ranolazine

Interventions

Ranolazine DRUG

Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated

Also known as: Ranexa

Ranolazine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• MWT 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boston University: lead
• Gilead Sciences: collaborator

Study Sites (1)

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Ventricular Dysfunction, Left

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Ventricular Dysfunction; Heart Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Small sample size; not all subjects completed Day 180 assessments

Results Point of Contact

• Title: Kimberly Finch
• Organization: Boston University

kimtobin@bu.edu

617-638-4475

Study Officials

• Harrison Farber, MD

  Boston University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 8, 2014
• Study Start: July 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2014
• Last Updated: May 17, 2017
• Results First Posted: May 17, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)