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

Myocardial Ischemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01221272
• Other study ID #: GS-US-259-0103
• Status: Completed
• Phase: Phase 4
• First received: October 13, 2010
• Last updated: August 21, 2014
• Start date: September 2010
• Est. completion date: September 2012

Study information

• Verified date: August 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardCanada: Health CanadaCanada: Ethics Review CommitteeCzech Republic: Ethics CommitteeCzech Republic: State Institute for Drug ControlFinland: Ethics CommitteeFinland: Finnish Medicines AgencyIsrael: Ethics CommissionIsrael: Israeli Health Ministry Pharmaceutical AdministrationItaly: Ethics CommitteeItaly: The Italian Medicines AgencySingapore: Domain Specific Review BoardsSingapore: Health Sciences AuthorityUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Myocardial Ischemia
• Myocardial Perfusion Imaging

Intervention

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)
• 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

Locations

Country	Name	City	State
Canada	ECOGENE-21 Clinical Trial Center, Chicoutimi Hospital	Chicoutimi	Quebec
Canada	Chum Hotel Dieu	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Czech Republic	University Hospital Kralovske Vinohrady	Praha 10
Czech Republic	University Hospital Motol	Praha 5
Finland	Turku University Hospital	Turku
Israel	Barzilai Medical Center	Ashkelon
Israel	Soroka Medical Center	Beer Sheva
Israel	Rambam Health Care Campus	Haifa
Israel	Kaplan Medical Center	Rehovot
Israel	Assuta MC	Tel Aviv
Italy	"Federico II" University	Naples
Italy	Federico II University	Naples
Singapore	National Heart Centre Singapore	Singapore
Singapore	National University Health System	Singapore
United Kingdom	Northwick Park Hospital, Watford Road	Middlesex
United States	Androscroggin Cardiology Associates DBA Maine Research Associates	Auburn	Maine
United States	Fox Valley Clinical Research Center, LLC	Aurora	Illinois
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Heritage Cardiology	Camp Hill	Pennsylvania
United States	Louisiana Heart Center	Covington	Louisiana
United States	Duke University Medical Center	Durham	North Carolina
United States	East Texas Cardiology PA	Houston	Texas
United States	Imperial Cardiac Center	Imperial	California
United States	Kore Cardiovascular Research	Jackson	Tennessee
United States	St. Luke's Cardiology Associates	Jacksonville	Florida
United States	Cardiovascular Imaging Technologies	Kansas City	Missouri
United States	Clinical Trials Research	Lincoln	California
United States	Dr. Michael Sacher	Massapequa	New York
United States	Cardiovascular Research Center of South Florida	Miami	Florida
United States	Mission Internal Medical Group	Mission Viejo	California
United States	Columbia University Medical Center	New York	New York
United States	Alfieri Cardiology	Newark	Delaware
United States	Research One	Orlando	Florida
United States	Research Integrity, LLC	Owensboro	Kentucky
United States	University of Pittsburgh Medical Center Cardiovascular Institute	Pittsburgh	Pennsylvania
United States	Central Coast Cardiology	Salinas	California
United States	Delmarva Heart Research Foundation, Inc	Salisbury	Maryland
United States	Mercury Medical, LLC	San Antonio	Texas
United States	Louisiana Heart Center	Slidell	Louisiana
United States	Cardiology Partners Clinical Research Institute	Wellington	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  Czech Republic,  Finland,  Israel,  Italy,  Singapore,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 33 days	No
Primary	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.	Up to 33 days	No
Secondary	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.	Up to 33 days	No
Secondary	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.	Up to 33 days	No
Secondary	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.	Up to 33 days	No