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

NCT01221272 | Completed Phase 4 Results

• 1 other identifier: GS-US-259-0103
• Study Type: interventional
• Target: 81
• Locations: 8 countries
• Sites: 43

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.

Conditions

Myocardial Perfusion Imaging; Myocardial Ischemia

Keywords

SPECT MPI

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (3)

• Perfusion Defect Severity at Baseline, End of Period 1, and End of Period 2

  Up to 33 days

• 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 Total Perfusion Deficit (TPD) at Baseline, End of Period 1, and End of Period 2

  Up to 33 days

Study Arms (2)

Ranolazine/Placebo

EXPERIMENTAL

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; Drug: Placebo to match ranolazine; Procedure: SPECT MPI; Behavioral: Exercise

Placebo/Ranolazine

EXPERIMENTAL

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; Drug: Placebo to match ranolazine; Procedure: SPECT MPI; Behavioral: Exercise

Interventions

Ranolazine DRUG

* 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)

Also known as: Ranexa®

Placebo/Ranolazine; Ranolazine/Placebo

Placebo to match ranolazine DRUG

Placebo to match ranolazine administered in the same form and frequency as the active drug.

Placebo/Ranolazine; Ranolazine/Placebo

SPECT MPI PROCEDURE

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.

Placebo/Ranolazine; Ranolazine/Placebo

Exercise BEHAVIORAL

Treadmill stress test

Placebo/Ranolazine; Ranolazine/Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (43)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Imperial Cardiac Center

Imperial, California, 92251, United States

Location

Clinical Trials Research

Lincoln, California, 95648, United States

Location

Mission Internal Medical Group

Mission Viejo, California, 92691, United States

Location

Central Coast Cardiology

Salinas, California, 93901, United States

Location

Alfieri Cardiology

Newark, Delaware, 19713, United States

Location

St. Luke's Cardiology Associates

Jacksonville, Florida, 32216, United States

Location

Cardiovascular Research Center of South Florida

Miami, Florida, 33173, United States

Location

Research One

Orlando, Florida, 32806, United States

Location

Cardiology Partners Clinical Research Institute

Wellington, Florida, 33449, United States

Location

Fox Valley Clinical Research Center, LLC

Aurora, Illinois, 60504, United States

Location

Research Integrity, LLC

Owensboro, Kentucky, 42303, United States

Location

Louisiana Heart Center

Covington, Louisiana, 70403, United States

Location

Louisiana Heart Center

Slidell, Louisiana, 70458, United States

Location

Androscroggin Cardiology Associates DBA Maine Research Associates

Auburn, Maine, 04210, United States

Location

Delmarva Heart Research Foundation, Inc

Salisbury, Maryland, 21804, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Cardiovascular Imaging Technologies

Kansas City, Missouri, 64111, United States

Location

Dr. Michael Sacher

Massapequa, New York, 11758, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Heritage Cardiology

Camp Hill, Pennsylvania, 17011, United States

Location

University of Pittsburgh Medical Center Cardiovascular Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

Kore Cardiovascular Research

Jackson, Tennessee, 38305, United States

Location

East Texas Cardiology PA

Houston, Texas, 77002, United States

Location

Mercury Medical, LLC

San Antonio, Texas, 78229, United States

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

ECOGENE-21 Clinical Trial Center, Chicoutimi Hospital

Chicoutimi, Quebec, G7H 7P2, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Chum Hotel Dieu

Montreal, Quebec, H2W 1T8, Canada

Location

University Hospital Kralovske Vinohrady

Prague, 100 34, Czechia

Location

University Hospital Motol

Prague, 150 06, Czechia

Location

Turku University Hospital

Turku, 20520, Finland

Location

Barzilai Medical Center

Ashkelon, 78278, Israel

Location

Soroka Medical Center

Beersheba, 84101, Israel

Location

Rambam Health Care Campus

Haifa, 31096, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Assuta MC

Tel Aviv, 69710, Israel

Location

"Federico II" University

Naples, 80131, Italy

Location

Federico II University

Naples, 80131, Italy

Location

National University Health System

Singapore, 119228, Singapore

Location

National Heart Centre Singapore

Singapore, 168752, Singapore

Location

Northwick Park Hospital, Watford Road

Middlesex, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Myocardial Ischemia

Interventions

Ranolazine; Exercise

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• Patrick Yue, MD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2010
• First Posted: October 14, 2010
• Study Start: September 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: September 3, 2014
• Results First Posted: September 3, 2014

Record last verified: 2014-08

Locations

GB (1); FI (1); CZ (2); IL (5); US (26); CA (4); SG (2); IT (2)