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A Study of Ranolazine Acute Administration and Short Term Administration in Pulmonary Arterial Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01757808
Recruitment Status : Completed
First Posted : December 31, 2012
Last Update Posted : March 3, 2017
Sponsor:
Information provided by (Responsible Party):
University of Chicago

Brief Summary:

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 or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: Ranolazine Drug: Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase I Study of Ranolazine Acute Administration and Short Term Administration in Pulmonary Arterial Hypertension
Study Start Date : August 2011
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2015


Arm Intervention/treatment
Experimental: Ranolazine Drug: Ranolazine
ranolazine sustained release at a dose of 500mg for one month followed by a dose of 1000mg.
Other Name: GS-9668

Placebo Comparator: Placebo Drug: Placebo
placebo at a dose of 500mg for one month followed by a dose of 1000mg.
Other Name: sugar pill




Primary Outcome Measures :
  1. Change in pulmonary vascular resistance (PVR) [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. Change in CPET (VE/VCO2, PETCO2, peak VO2, peak HR, peak RER, work max (MET or Watt), sub maximum exercise time [ Time Frame: 12 weeks ]
  2. Change in RV echo parameters: 2D, 3D [ Time Frame: 12 weeks ]
  3. Change in 6MWD [ Time Frame: 12 weeks ]
  4. Safety/SAE [ Time Frame: 12 weeks ]
    AE and SAE on study drug and acutely changes in blood pressure and PAP



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 72 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 estimated glomerular filtration rate (eGFR) less than 45 mL/min/BSA (where BSA=1.73m2) as calculated by the Modification of Diet in Renal Disease (MDRD) equation:

Patients with eGFR 45-50 mL/min/BSA may be enrolled only after discussion with data safety monitoring board. Patients with eGFR ≥ 50 mL/min/BSA may be enrolled without such a discussion.

  • 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 with left ventricular ejection fraction <45% or left ventricular shortening fraction <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.

Information from the National Library of Medicine

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): NCT01757808


Locations
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United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
Investigators
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Principal Investigator: Mardi Gomberg-Maitland, MD University of Chicago
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT01757808    
Other Study ID Numbers: 11-0301
First Posted: December 31, 2012    Key Record Dates
Last Update Posted: March 3, 2017
Last Verified: March 2017
Keywords provided by University of Chicago:
PAH
Ranolazine
right ventricle
Safety
cardiopulmonary exercise testing
Additional relevant MeSH terms:
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Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Ranolazine
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action