Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Effect of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01221272
First received: October 13, 2010
Last updated: August 21, 2014
Last verified: August 2014
  Purpose

This study enrolled participants with documented exercise-induced myocardial ischemia in order to evaluate whether ranolazine, when taken prior to exercise, can improve blood flow to the heart (myocardial perfusion), as assessed by exercise-induced myocardial perfusion defect size (PDS) and total perfusion deficit (TPD), using gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).

This was a 2-period crossover study. The last dose of each period must have been taken 3-4 hours prior to conduct of the exercise SPECT MPI. After the research exercise SPECT MPI was performed at the end of Period 1, participants discontinued the treatment they were randomized to for that period and began the other treatment in Period 2.


Condition Intervention Phase
Myocardial Perfusion Imaging
Myocardial Ischemia
Drug: Ranolazine
Drug: Placebo to match ranolazine
Procedure: SPECT MPI
Behavioral: Exercise
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 4, Randomized, Double-Blind, Placebo-Controlled, Cross-over Trial to Evaluate the Effects of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Exercise-induced Perfusion Defect Size (PDS) Following Ranolazine and Placebo Treatment [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
    PDS is the amount (percent) of the myocardium with decreased blood flow. A lower percentage means more of the myocardium is receiving blood flow. Measurements were obtained by gated single photon emission computed tomography (SPECT) imaging following exercise at the end of the ranolazine and placebo treatment periods.

  • Exercise-induced Total Perfusion Deficit (TPD) Following Ranolazine and Placebo Treatment [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
    TPD is a score that measures the overall impact of a region of decreased myocardial blood flow, incorporating both the amount and severity of the decreased flow. TPD is measured on a scale of 0-100, with higher scores being worse and lower scores being better. Measurements were obtained by SPECT imaging following exercise at the end of the ranolazine and placebo treatment periods.


Secondary Outcome Measures:
  • Perfusion Defect Severity at Baseline, End of Period 1, and End of Period 2 [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
    Perfusion defect severity was assessed for each participant as the percentage of the 17 myocardium segments with a relative perfusion defect score of 3 or 4 on a 0-4 scale. Segment scores are: 0 = normal perfusion; 1 = mild reduction in counts-not definitely abnormal; 2 = moderate reduction in counts-definitely abnormal; 3 = severe reduction in counts; 4 = absent uptake (lower scores correspond to less severity and higher scores correspond to increased severity). A lower percentage means fewer segments have severely reduced blood flow. Measurements were obtained by SPECT imaging following exercise at baseline and at the end of Periods 1 and 2.

  • Exercise-induced Reversible Perfusion Defect Size (PDS) at Baseline, End of Period 1, and End of Period 2 [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
    Exercise-induced reversible PDS was derived as the exercise PDS at baseline and at the end of Periods 1 and 2 minus the resting PDS at baseline. A lower percentage means more of the myocardium is receiving blood flow. Measurements were obtained by SPECT imaging at baseline both at rest and following exercise and following exercise at the end of Periods 1 and 2.

  • Exercise-induced Reversible Total Perfusion Deficit (TPD) at Baseline, End of Period 1, and End of Period 2 [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
    Exercise-induced reversible TPD was derived as the exercise TPD at baseline and at the end of Periods 1 and 2 minus the resting TPD at baseline. TPD is measured on a scale of 0-100, with higher scores being worse and lower scores being better. Measurements were obtained by SPECT imaging at baseline both at rest and following exercise and following exercise at the end of Periods 1 and 2.


Enrollment: 81
Study Start Date: September 2010
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ranolazine/Placebo
Participants received ranolazine from Day 1 through Day 15 (± 2 days) of Period 1, followed by an exercise SPECT MPI study, then received placebo to match ranolazine from Day 1 through Day 15 (± 2 days) of Period 2, followed by an exercise SPECT MPI study.
Drug: Ranolazine
  • One 500 mg tablet in the evening on Day 1 of the period
  • One 500 mg tablet, twice daily on Days 2-3 of the period
  • Two 500 mg tablets (1000 mg total), twice daily from Day 4 to the end of the period (Day 15 ± 2 days)
Other Name: Ranexa®
Drug: Placebo to match ranolazine
Placebo to match ranolazine administered in the same form and frequency as the active drug.
Procedure: SPECT MPI
Gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to confirm the presence of reversible exercise-induced left ventricular perfusion defect size (PDS) performed within 12 weeks prior to baseline or at the baseline visit, and at the end-of-period 1 and end-of-period 2 visits.
Behavioral: Exercise
Treadmill stress test
Experimental: Placebo/Ranolazine
Participants received placebo to match ranolazine from Day 1 through Day 15 (± 2 days) of Period 1, followed by an exercise SPECT MPI study, then received ranolazine from Day 1 through Day 15 (± 2 days) of Period 2, followed by an exercise SPECT MPI study.
Drug: Ranolazine
  • One 500 mg tablet in the evening on Day 1 of the period
  • One 500 mg tablet, twice daily on Days 2-3 of the period
  • Two 500 mg tablets (1000 mg total), twice daily from Day 4 to the end of the period (Day 15 ± 2 days)
Other Name: Ranexa®
Drug: Placebo to match ranolazine
Placebo to match ranolazine administered in the same form and frequency as the active drug.
Procedure: SPECT MPI
Gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to confirm the presence of reversible exercise-induced left ventricular perfusion defect size (PDS) performed within 12 weeks prior to baseline or at the baseline visit, and at the end-of-period 1 and end-of-period 2 visits.
Behavioral: Exercise
Treadmill stress test

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Exercise SPECT MPI study (stress and rest) showing at least 10% reversible myocardial ischemia (as confirmed by the core nuclear laboratory using Corridor4DM imaging software) performed not more than 12 weeks prior to screening, OR
  • Exercise SPECT MPI study (stress and rest) conducted during screening (after consultation with the Medical Monitor and after informed consent was obtained) showing at least 10% reversible myocardial ischemia (as confirmed by the core nuclear laboratory)
  • Stable antianginal medical therapy (excluding short-acting nitroglycerin)

Key Exclusion Criteria:

  • Left bundle branch block
  • Automated implantable defibrillator and/or pacemaker (selected subjects with permanent pacemakers who had an intact sinus mechanism may have been included following consultation with the Medical Monitor)
  • Intervening coronary revascularization between the time of qualifying exercise SPECT MPI study and randomization
  • Acute myocardial infarction (MI) within 60 days prior to screening or at any time after the qualifying exercise SPECT MPI study, or MI undergoing staged intervention during a subject's participation in the trial
  • Unstable angina within 30 days prior to screening, or at any time after the qualifying exercise SPECT MPI study
  • Coronary artery bypass graft surgery within 60 days prior to screening or at any time after the qualifying exercise SPECT MPI study, or percutaneous coronary intervention within 30 days prior to screening or at any time after the qualifying exercise SPECT MPI study
  • Anticipated coronary revascularization during the trial period
  • Cerebrovascular attack or transient ischemic attack within 90 days prior to screening
  • History of serious arrhythmias
  • Current atrial fibrillation or atrial flutter
  • QTc interval > 500 milliseconds
  • Diagnosed as having New York Heart Association Class III or IV heart failure
  • Inability to exercise or exercise limitation due to other comorbidities that may have interfered with ability to perform required exercise SPECT MPI study
  • Body mass index greater than or equal to 38 kg/m^2 (may have been up to 40 kg/m^2 after consultation with the Medical Monitor)
  • Any absolute contraindications to exercise stress testing
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01221272

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Imperial Cardiac Center
Imperial, California, United States, 92251
Clinical Trials Research
Lincoln, California, United States, 95648
Mission Internal Medical Group
Mission Viejo, California, United States, 92691
Central Coast Cardiology
Salinas, California, United States, 93901
United States, Delaware
Alfieri Cardiology
Newark, Delaware, United States, 19713
United States, Florida
St. Luke's Cardiology Associates
Jacksonville, Florida, United States, 32216
Cardiovascular Research Center of South Florida
Miami, Florida, United States, 33173
Research One
Orlando, Florida, United States, 32806
Cardiology Partners Clinical Research Institute
Wellington, Florida, United States, 33449
United States, Illinois
Fox Valley Clinical Research Center, LLC
Aurora, Illinois, United States, 60504
United States, Kentucky
Research Integrity, LLC
Owensboro, Kentucky, United States, 42303
United States, Louisiana
Louisiana Heart Center
Covington, Louisiana, United States, 70403
Louisiana Heart Center
Slidell, Louisiana, United States, 70458
United States, Maine
Androscroggin Cardiology Associates DBA Maine Research Associates
Auburn, Maine, United States, 04210
United States, Maryland
Delmarva Heart Research Foundation, Inc
Salisbury, Maryland, United States, 21804
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Missouri
Cardiovascular Imaging Technologies
Kansas City, Missouri, United States, 64111
United States, New York
Dr. Michael Sacher
Massapequa, New York, United States, 11758
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Heritage Cardiology
Camp Hill, Pennsylvania, United States, 17011
University of Pittsburgh Medical Center Cardiovascular Institute
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Kore Cardiovascular Research
Jackson, Tennessee, United States, 38305
United States, Texas
East Texas Cardiology PA
Houston, Texas, United States, 77002
Mercury Medical, LLC
San Antonio, Texas, United States, 78229
Canada, Ontario
University of Ottawa Heart Institute
Ottawa, Ontario, Canada, K1Y 4W7
Canada, Quebec
ECOGENE-21 Clinical Trial Center, Chicoutimi Hospital
Chicoutimi, Quebec, Canada, G7H 7P2
Chum Hotel Dieu
Montreal, Quebec, Canada, H2W 1T8
Montreal Heart Institute
Montreal, Quebec, Canada, H1T 1C8
Czech Republic
University Hospital Kralovske Vinohrady
Praha 10, Czech Republic, 100 34
University Hospital Motol
Praha 5, Czech Republic, 150 06
Finland
Turku University Hospital
Turku, Finland, 20520
Israel
Barzilai Medical Center
Ashkelon, Israel, 78278
Soroka Medical Center
Beer Sheva, Israel, 84101
Rambam Health Care Campus
Haifa, Israel, 31096
Kaplan Medical Center
Rehovot, Israel, 76100
Assuta MC
Tel Aviv, Israel, 69710
Italy
"Federico II" University
Naples, Italy, 80131
Federico II University
Naples, Italy, 80131
Singapore
National Heart Centre Singapore
Singapore, Singapore, 168752
National University Health System
Singapore, Singapore, 119228
United Kingdom
Northwick Park Hospital, Watford Road
Middlesex, United Kingdom, HA1 3UJ
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Patrick Yue, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01221272     History of Changes
Other Study ID Numbers: GS-US-259-0103
Study First Received: October 13, 2010
Results First Received: July 1, 2014
Last Updated: August 21, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Canada: Health Canada
Canada: Ethics Review Committee
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Finland: Ethics Committee
Finland: Finnish Medicines Agency
Israel: Ethics Commission
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: Ethics Committee
Italy: The Italian Medicines Agency
Singapore: Domain Specific Review Boards
Singapore: Health Sciences Authority
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Gilead Sciences:
SPECT MPI

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Coronary Disease
Heart Diseases
Vascular Diseases
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 20, 2014