A Study of Ranolazine Acute Administration and Short Term Administration in Pulmonary Arterial Hypertension - Full Text View

Purpose

The purpose of this study is to assess the safety of ranolazine in people with pulmonary arterial hypertension (PAH) and who are receiving 1 or more background PAH therapies: ambrisentan, sildenafil,tadalafil, epoprostenol, treprostinil (IV, SC, inhaled), or iloprost. The primary objective is:

To estimate the effect of ranolazine administration on acute hemodynamics.
To assess safety of ranolazine acutely over 6 hrs in the catheterization lab and after 12 weeks of therapy
To assess changes in right ventricular function after 12 weeks of therapy.

Condition	Intervention	Phase
Pulmonary Arterial Hypertension	Drug: Ranolazine Drug: Placebo	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Phase I Study of Ranolazine Acute Administration and Short Term Administration in Pulmonary Arterial Hypertension

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: Exercise and Physical Fitness High Blood Pressure

Drug Information available for: Ranolazine

U.S. FDA Resources

Further study details as provided by University of Chicago:

Primary Outcome Measures:

Ranolazine will lower pulmonary vascular resistance (PVR) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

- Change in CPET (VE/VCO2, PETCO2, peak VO2, peak HR, peak RER, work max (MET or Watt), sub maximum exercise time at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Change in RV echo parameters: 2D, 3D [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Change in 6MWD [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Safety/SAE [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
AE and SAE on study drug and acutely changes in blood pressure and PAP

Estimated Enrollment:	16
Study Start Date:	August 2011
Estimated Study Completion Date:	August 2013
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ranolazine	Drug: Ranolazine ranolazine sustained release at a dose of 500mg. Other Name: GS-9668
Placebo Comparator: Placebo	Drug: Placebo placebo at a dose of 500mg. Other Name: sugar pill

Detailed Description:

Pulmonary arterial hypertension is a medical disorder in which pressure in the blood vessels going from the right side of the heart to the lungs is higher than normal. The increased blood pressure in the lungs places a strain on the heart. This strain causes the heart to pump less blood into the lungs, causing physical symptoms of shortness of breath and tiredness. The added strain to the heart can cause physical symptoms of swelling in the feet and abdomen. These symptoms can get worse over time due to the decreased pumping ability of the heart.

This study will use a drug called ranolazine. This drug has been approved by the Food and Drug Administration (FDA) to treat chronic angina (chest pain). However, since it has not been approved for use in PAH its use in this study is considered experimental.

Eligibility

Ages Eligible for Study:	18 Years to 72 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

All subjects age 18-72 yrs will have a diagnosis of PAH. PAH as defined as idiopathic PAH, heritable PAH or PAH associated with collagen vascular disease, congenital heart disease (repaired), or anorexigen use. A history of PAH as defined by hemodynamics at diagnosis by right heart catheterization defined as: mean PAP >25 mmHg with a normal PCWP < 15 mm Hg at rest and a PVR >3 Wood units.
Baseline 6MW >150 meters
Patients will be receiving FDA approved PAH monotherapy or dual therapy medications: including, ambrisentan (5,10mg), sildenafil (60-240mg), tadalafil (40mg), epoprostenol, treprostinil, or iloprost at stable doses for >90days.
Receiving conventional therapy as clinically indicated (oxygen, calcium channel blockers, digoxin) with dose that is unchanged in the preceding 30 days prior to enrollment. This is excluding anticoagulants (warfarin) as the patient's dose may not be stable if the patient is having a cardiac catheterization at baseline within 30 days of enrollment and warfarin is being held.

Exclusion Criteria:

PAH Category II-IV and Category I associated with all other etiologies: HIV, portopulmonary disease
All subjects on monotherapy calcium blockers as "calcium blocker responders" irrespective of therapy
All subjects receiving CY3P4 inducer (i.e. bosentan)
Subjects with pulmonary hypertension due to significant interstitial lung disease, chronic obstructive pulmonary disease, congestive heart failure, valvular heart disease
Subjects with (World Health Organization (WHO) functional Class I or Class IV
Subjects with total lung capacity (TLC) < 60% of predicted
Subjects with significant obstructive lung disease with FEV1/FVC ratio < 70% of predicted
Subjects with hypotension defined as systolic arterial pressure < 90 mmHg at baseline
Subjects with hypertension defined as systolic arterial pressure >140 mmHg at baseline and a diastolic arterial pressure > 90 mmHg despite adequate medical therapy.
Subjects with impaired renal function as defined as creatinine clearance <30 ml/min as defined by the Cockcroft-Gault formula: Male: Creatinine clearance (ml/min)= (140-age) x (body weight in kg)/ (72x serum creatinine in mg/dl); Female: Creatinine clearance (ml/min)= 0.85 (140-age) x (body weight in kg)/ (72x serum creatinine in mg/dl)
Subjects with liver function tests (transaminases (AST/ALT), total bilirubin, and alkaline phosphatase) >2X normal values
Subjects with acutely decompensated heart failure requiring hospitalization or medication adjustment or hospitalization for any cause within the previous 30 days prior to screening
Subjects may not be receiving any other investigational agents
Subjects without having taken an serotonin reuptake inhibitor within 3-5 months
Subjects with left ventricular ejection fraction <45% or left ventricular shortening fracton <0.2
Subjects with acute myocardial infarction within 90 days prior to screening
Subjects taking nitrates for any medical problem
Subjects with a recent (<180 days) history of pulmonary embolism verified by ventilation/perfusion scan, angiogram or spiral CT scan
Pregnant or lactating women
Subjects with a history of current drug abuse including alcohol
History of gastric bypass surgery
History of sinus or atrioventricular nodal disease ie. sick sinus syndrome, or second or third degree heart block.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01757808

Contacts

Contact: Mardi Gomberg-Maitland, MD

773-702-5589

mgomberg@medicine.bsd.uchicago.edu

Locations

United States, Illinois
University of Chicago	Recruiting
Chicago, Illinois, United States, 60637
Principal Investigator: Mardi Gomberg-Maitland, MD

Sponsors and Collaborators

University of Chicago

Investigators

Principal Investigator:

Mardi Gomberg-Maitland, MD

University of Chicago

More Information

No publications provided

Responsible Party:	Mardi Gomberg-Maitland, Mardi Gomberg-Maitland, MD, M.Sc, University of Chicago
ClinicalTrials.gov Identifier:	NCT01757808 History of Changes
Other Study ID Numbers:	11-0301
Study First Received:	April 26, 2012
Last Updated:	December 21, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Chicago:

PAH
Ranolazine
right ventricle
Safety
cardiopulmonary exercise testing

Additional relevant MeSH terms:

Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases

Cardiovascular Diseases
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013