Back to resultsEffect of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging
Primary Purpose
Myocardial Perfusion Imaging, Myocardial Ischemia
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Ranolazine
Placebo to match ranolazine
SPECT MPI
Exercise
Sponsored by
About this trial
This is an interventional treatment trial for Myocardial Perfusion Imaging focused on measuring SPECT MPI
Eligibility 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
Sites / Locations
- University of Alabama at Birmingham
- Imperial Cardiac Center
- Clinical Trials Research
- Mission Internal Medical Group
- Central Coast Cardiology
- Alfieri Cardiology
- St. Luke's Cardiology Associates
- Cardiovascular Research Center of South Florida
- Research One
- Cardiology Partners Clinical Research Institute
- Fox Valley Clinical Research Center, LLC
- Research Integrity, LLC
- Louisiana Heart Center
- Louisiana Heart Center
- Androscroggin Cardiology Associates DBA Maine Research Associates
- Delmarva Heart Research Foundation, Inc
- Massachusetts General Hospital
- Cardiovascular Imaging Technologies
- Dr. Michael Sacher
- Columbia University Medical Center
- Duke University Medical Center
- Heritage Cardiology
- University of Pittsburgh Medical Center Cardiovascular Institute
- Kore Cardiovascular Research
- East Texas Cardiology PA
- Mercury Medical, LLC
- University of Ottawa Heart Institute
- ECOGENE-21 Clinical Trial Center, Chicoutimi Hospital
- Montreal Heart Institute
- Chum Hotel Dieu
- University Hospital Kralovske Vinohrady
- University Hospital Motol
- Turku University Hospital
- Barzilai Medical Center
- Soroka Medical Center
- Rambam Health Care Campus
- Kaplan Medical Center
- Assuta MC
- "Federico II" University
- Federico II University
- National University Health System
- National Heart Centre Singapore
- Northwick Park Hospital, Watford Road
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Ranolazine/Placebo
Placebo/Ranolazine
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Exercise-induced Perfusion Defect Size (PDS) Following Ranolazine and Placebo Treatment
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
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01221272
Brief Title
Effect of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
September 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Perfusion Imaging, Myocardial Ischemia
Keywords
SPECT MPI
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
81 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ranolazine/Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo/Ranolazine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ranolazine
Other Intervention Name(s)
Ranexa®
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Placebo to match ranolazine
Intervention Description
Placebo to match ranolazine administered in the same form and frequency as the active drug.
Intervention Type
Procedure
Intervention Name(s)
SPECT MPI
Intervention Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Exercise
Intervention Description
Treadmill stress test
Primary Outcome Measure Information:
Title
Exercise-induced Perfusion Defect Size (PDS) Following Ranolazine and Placebo Treatment
Description
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.
Time Frame
Up to 33 days
Title
Exercise-induced Total Perfusion Deficit (TPD) Following Ranolazine and Placebo Treatment
Description
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.
Time Frame
Up to 33 days
Secondary Outcome Measure Information:
Title
Perfusion Defect Severity at Baseline, End of Period 1, and End of Period 2
Description
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.
Time Frame
Up to 33 days
Title
Exercise-induced Reversible Perfusion Defect Size (PDS) at Baseline, End of Period 1, and End of Period 2
Description
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.
Time Frame
Up to 33 days
Title
Exercise-induced Reversible Total Perfusion Deficit (TPD) at Baseline, End of Period 1, and End of Period 2
Description
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.
Time Frame
Up to 33 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Yue, MD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Imperial Cardiac Center
City
Imperial
State/Province
California
ZIP/Postal Code
92251
Country
United States
Facility Name
Clinical Trials Research
City
Lincoln
State/Province
California
ZIP/Postal Code
95648
Country
United States
Facility Name
Mission Internal Medical Group
City
Mission Viejo
State/Province
California
ZIP/Postal Code
92691
Country
United States
Facility Name
Central Coast Cardiology
City
Salinas
State/Province
California
ZIP/Postal Code
93901
Country
United States
Facility Name
Alfieri Cardiology
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
St. Luke's Cardiology Associates
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Cardiovascular Research Center of South Florida
City
Miami
State/Province
Florida
ZIP/Postal Code
33173
Country
United States
Facility Name
Research One
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Cardiology Partners Clinical Research Institute
City
Wellington
State/Province
Florida
ZIP/Postal Code
33449
Country
United States
Facility Name
Fox Valley Clinical Research Center, LLC
City
Aurora
State/Province
Illinois
ZIP/Postal Code
60504
Country
United States
Facility Name
Research Integrity, LLC
City
Owensboro
State/Province
Kentucky
ZIP/Postal Code
42303
Country
United States
Facility Name
Louisiana Heart Center
City
Covington
State/Province
Louisiana
ZIP/Postal Code
70403
Country
United States
Facility Name
Louisiana Heart Center
City
Slidell
State/Province
Louisiana
ZIP/Postal Code
70458
Country
United States
Facility Name
Androscroggin Cardiology Associates DBA Maine Research Associates
City
Auburn
State/Province
Maine
ZIP/Postal Code
04210
Country
United States
Facility Name
Delmarva Heart Research Foundation, Inc
City
Salisbury
State/Province
Maryland
ZIP/Postal Code
21804
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Cardiovascular Imaging Technologies
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Dr. Michael Sacher
City
Massapequa
State/Province
New York
ZIP/Postal Code
11758
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Heritage Cardiology
City
Camp Hill
State/Province
Pennsylvania
ZIP/Postal Code
17011
Country
United States
Facility Name
University of Pittsburgh Medical Center Cardiovascular Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Kore Cardiovascular Research
City
Jackson
State/Province
Tennessee
ZIP/Postal Code
38305
Country
United States
Facility Name
East Texas Cardiology PA
City
Houston
State/Province
Texas
ZIP/Postal Code
77002
Country
United States
Facility Name
Mercury Medical, LLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada
Facility Name
ECOGENE-21 Clinical Trial Center, Chicoutimi Hospital
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 7P2
Country
Canada
Facility Name
Montreal Heart Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 1C8
Country
Canada
Facility Name
Chum Hotel Dieu
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1T8
Country
Canada
Facility Name
University Hospital Kralovske Vinohrady
City
Praha 10
ZIP/Postal Code
100 34
Country
Czech Republic
Facility Name
University Hospital Motol
City
Praha 5
ZIP/Postal Code
150 06
Country
Czech Republic
Facility Name
Turku University Hospital
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Barzilai Medical Center
City
Ashkelon
ZIP/Postal Code
78278
Country
Israel
Facility Name
Soroka Medical Center
City
Beer Sheva
ZIP/Postal Code
84101
Country
Israel
Facility Name
Rambam Health Care Campus
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Kaplan Medical Center
City
Rehovot
ZIP/Postal Code
76100
Country
Israel
Facility Name
Assuta MC
City
Tel Aviv
ZIP/Postal Code
69710
Country
Israel
Facility Name
"Federico II" University
City
Naples
ZIP/Postal Code
80131
Country
Italy
Facility Name
Federico II University
City
Naples
ZIP/Postal Code
80131
Country
Italy
Facility Name
National University Health System
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Facility Name
National Heart Centre Singapore
City
Singapore
ZIP/Postal Code
168752
Country
Singapore
Facility Name
Northwick Park Hospital, Watford Road
City
Middlesex
ZIP/Postal Code
HA1 3UJ
Country
United Kingdom
12. IPD Sharing Statement
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Effect of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging
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