Effect of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging
- Conditions
- Myocardial Perfusion ImagingMyocardial Ischemia
- Interventions
- Registration Number
- NCT01221272
- Lead Sponsor
- Gilead Sciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 81
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo/Ranolazine Exercise 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. Ranolazine/Placebo SPECT MPI 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. Placebo/Ranolazine SPECT MPI 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. Ranolazine/Placebo Placebo to match ranolazine 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. Ranolazine/Placebo Exercise 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. Placebo/Ranolazine Placebo to match 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. Ranolazine/Placebo Ranolazine 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. Placebo/Ranolazine 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.
- Primary Outcome Measures
Name Time Method Exercise-induced Perfusion Defect Size (PDS) Following Ranolazine and Placebo Treatment Up to 33 days 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 Up to 33 days 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
Name Time Method Perfusion Defect Severity at Baseline, End of Period 1, and End of Period 2 Up to 33 days 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 Up to 33 days 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 Up to 33 days 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.
Trial Locations
- Locations (42)
Columbia University Medical Center
🇺🇸New York, New York, United States
Chum Hotel Dieu
🇨🇦Montreal, Quebec, Canada
Turku University Hospital
🇫🇮Turku, Finland
University Hospital Kralovske Vinohrady
🇨🇿Praha 10, Czech Republic
University Hospital Motol
🇨🇿Praha 5, Czech Republic
National University Health System
🇸🇬Singapore, Singapore
Northwick Park Hospital, Watford Road
🇬🇧Middlesex, United Kingdom
Cardiovascular Imaging Technologies
🇺🇸Kansas City, Missouri, United States
Clinical Trials Research
🇺🇸Lincoln, California, United States
Mission Internal Medical Group
🇺🇸Mission Viejo, California, United States
ECOGENE-21 Clinical Trial Center, Chicoutimi Hospital
🇨🇦Chicoutimi, Quebec, Canada
Montreal Heart Institute
🇨🇦Montreal, Quebec, Canada
Louisiana Heart Center
🇺🇸Slidell, Louisiana, United States
Delmarva Heart Research Foundation, Inc
🇺🇸Salisbury, Maryland, United States
"Federico II" University
🇮🇹Naples, Italy
Federico II University
🇮🇹Naples, Italy
Dr. Michael Sacher
🇺🇸Massapequa, New York, United States
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Soroka Medical Center
🇮🇱Beer Sheva, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Rambam Health Care Campus
🇮🇱Haifa, Israel
Assuta MC
🇮🇱Tel Aviv, Israel
National Heart Centre Singapore
🇸🇬Singapore, Singapore
St. Luke's Cardiology Associates
🇺🇸Jacksonville, Florida, United States
Cardiology Partners Clinical Research Institute
🇺🇸Wellington, Florida, United States
University of Ottawa Heart Institute
🇨🇦Ottawa, Ontario, Canada
Kore Cardiovascular Research
🇺🇸Jackson, Tennessee, United States
Androscroggin Cardiology Associates DBA Maine Research Associates
🇺🇸Auburn, Maine, United States
Central Coast Cardiology
🇺🇸Salinas, California, United States
Alfieri Cardiology
🇺🇸Newark, Delaware, United States
Heritage Cardiology
🇺🇸Camp Hill, Pennsylvania, United States
Fox Valley Clinical Research Center, LLC
🇺🇸Aurora, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Imperial Cardiac Center
🇺🇸Imperial, California, United States
Cardiovascular Research Center of South Florida
🇺🇸Miami, Florida, United States
Research One
🇺🇸Orlando, Florida, United States
Research Integrity, LLC
🇺🇸Owensboro, Kentucky, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University of Pittsburgh Medical Center Cardiovascular Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Mercury Medical, LLC
🇺🇸San Antonio, Texas, United States
East Texas Cardiology PA
🇺🇸Houston, Texas, United States