Ranolazine for Incomplete Vessel Revascularization Post-Percutaneous Coronary Intervention (PCI) (RIVER-PCI)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Effects of Ranolazine on Major Adverse Cardiovascular Events in Subjects With a History of Chronic Angina Who Undergo Percutaneous Coronary Intervention With Incomplete Revascularization

This study will evaluate the efficacy of ranolazine as compared with placebo when used as part of standard medical therapy in chronic angina subjects with incomplete revascularization post-percutaneous coronary intervention (PCI; formerly known as angioplasty with stent) on the composite of ischemia-driven revascularization or ischemia-driven hospitalization without revascularization.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Angina Pectoris
• Intervention / Treatment: Drug: Ranolazine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 2651
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Lower Austria
    • Saint Pölten, Lower Austria, Austria, 3100
      • Landesklinikum Sankt Pölten
  • Styria
    • Graz, Styria, Austria, 8020
      • Landeskrankenhaus Graz West
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Innsbruck Universitaetsklinik
  • Upper Austria
    • Linz, Upper Austria, Austria, 4020
      • Allgemeines Krankenhaus der Stadt Linz
  • Vienna
    • Wien, Vienna, Austria, 1090
      • Medizinische Universität Wien
    • Wien, Vienna, Austria, 1160
      • Wilhelminenspital der Stadt Wien
• Belgium
  • Liege, Belgium, 4000
    • Centre Hospitalier Universitaire Sart Tilman Liège
  • Antwerpen
    • Antwerp, Antwerpen, Belgium, 2020
      • Ziekenhuis Netwerk Antwerpen Middelheim
    • Bonheiden, Antwerpen, Belgium, 2820
      • Imelda Ziekenhuis
  • Limburg
    • Genk, Limburg, Belgium, 3600
      • ZOL Genk, Campus Saint Jan
  • West-Vlaanderen
    • Brugge, West-Vlaanderen, Belgium, 8000
      • Algemeen Ziekenhuis Sint-Jan
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
    • Edmonton, Alberta, Canada, T5H 3V9
      • Royal Alexandra Hospital
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • New Brunswick Heart Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences, General Site
    • Scarborough, Ontario, Canada, M1E 5E9
      • Scarborough Cardiology Research Associates
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network
    • Toronto, Ontario, Canada, M5B 1W8
      • Saint Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2W 1T8
      • Centre Hospitalier de l'Université de Montréal (CHUM)
    • Montréal, Quebec, Canada, H4J 1C5
      • Hôpital du Sacré-Coeur de Montréal
    • Montréal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
    • Quebec City, Quebec, Canada, G1V 4G5
      • Institut Universitaire De Cardiologie Et De Pneumologie De Québec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
• Czech Republic
  • Brno, Czech Republic, 625 00
    • Fakultni nemocnice Brno
  • Brno, Czech Republic, 656 91
    • Fakultni nemocnice u sv. Anny v Brne
  • Olomoucký kraj, Czech Republic, 775 20
    • Fakultni nemocnice Olomouc
  • Praha, Czech Republic, 150 06
    • Fakultni nemocnice v Motole
  • Praha, Czech Republic, 100 34
    • Fakultni nemocnice Kralovske Vinohrady
  • Praha, Czech Republic, 128 08
    • Vseobecna Fakultni Nemocnice V Praze
  • Karlovarský kraj
    • Karlovy Vary, Karlovarský kraj, Czech Republic, 360 66
      • Karlovarska krajska nemocnice a.s.
  • Liberecký kraj
    • Liberec, Liberecký kraj, Czech Republic, 460 63
      • Krajská nemocnice Liberec a.s.
• France
  • Paris, France, 75013
    • Groupe Hospitalier la Pitié Salpêtrière
  • Ile-de-France
    • Paris, Ile-de-France, France, 75018
      • Hopital Bichat-Claude Bernard
  • Midi-Pyrenees
    • Toulouse Cedex 9, Midi-Pyrenees, France, 31059
      • Hopital Rangueil
  • Nord Pas-De-Calais
    • Arras, Nord Pas-De-Calais, France, 62022
      • Centre Hospitalier D'arras
  • Rhone-Alpes
    • Pringy, Rhone-Alpes, France, 74374
      • Centre Hospitalier d'Annecy
• Germany
  • Berlin, Germany, 10249
    • Vivantes Klinikum im Friedrichshain
  • Baden-Wuerttemberg
    • Heidelberg, Baden-Wuerttemberg, Germany, 69120
      • Universitätsklinikum Heidelberg
  • Hessen
    • Bad Nauheim, Hessen, Germany, 61231
      • Kerckhoff-Klinik GmbH
    • Langen, Hessen, Germany, 63225
      • Asklepios-Kliniken Langen
  • Nordrhein-westfalen
    • Bielefeld, Nordrhein-westfalen, Germany, 33604
      • Städtische Kliniken Bielefeld gGmbH
    • Dortmund, Nordrhein-westfalen, Germany, 44137
      • Sankt Johannes Hospital
    • Mönchengladbach, Nordrhein-westfalen, Germany, 41063
      • Kliniken Maria Hilf GmbH
  • Rheinland-pfalz
    • Trier, Rheinland-pfalz, Germany, 54292
      • Krankenhaus der Barmherzigen Brüder Trier
• Israel
  • Afula, Israel, 18101
    • Haemek Medical Center
  • Ashkelon, Israel, 78287
    • Barzilai Medical Center
  • Beer Yahkov, Israel, 70300
    • Assaf Harofeh Medical Centre
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Haifa, Israel, 33394
    • Bnai Zion Medical Center
  • Holon, Israel, 58100
    • Edith Wolfson Medical Center
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Ein-Kerem Medical Centre
  • Kfar Saba, Israel, 44281
    • Meir Medical Center
  • Nahariya, Israel, 22100
    • Western Galilee Hospital
  • Ramat Gan, Israel
    • Hillel Yaffe Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Souraski Medical Center
  • Tel Hashomer, Israel, 52621
    • Sheba Medical Center
  • Zafed, Israel, 13100
    • ZIV Medical Center
  • Reheoboth
    • Rehovot, Reheoboth, Israel, 76100
      • Kaplan Medical Center
• Italy
  • Bergamo, Italy, 24128
    • Ospedali Riuniti di Bergamo
  • Caserta, Italy, 81100
    • Azienda Ospedaliera S. Sebastiano di Caserta
  • Firenze, Italy, 50134
    • Azienda Ospedaliero-Universitaria Careggi
  • Genova, Italy, 16132
    • Azienda Ospedaliera Universitaria San Martino
  • Milano, Italy, 20132
    • Fondazione Centro S. Raffaele del Monte Tabor, Ospedale San Raffaele
  • Novara, Italy, 28100
    • Azienda Ospedaliera "Maggiore della Carità" di Novara
  • Palermo, Italy, 90127
    • A.R.N.A.S. Civico G. Di Cristina Benfratelli
  • Parma, Italy, 43100
    • Azienda Ospedaliero Universitaria di Parma
  • Sassari, Italy, 07100
    • Ospedale Civile SS Annunziata ASL 1
• Netherlands
  • Gelderland, Netherlands, 6815 AD
    • Ziekenhuis Rijnstate Arnhem
  • Noord-brabant
    • Eindhoven, Noord-brabant, Netherlands, 5623 EJ
      • Catharina Ziekenhuis
    • Tilburg, Noord-brabant, Netherlands, 5042 AD
      • TweeSteden Ziekenhuis
  • Noord-holland
    • Amsterdam, Noord-holland, Netherlands, 1105 AZ
      • Academisch Medisch Centrum
  • Zuid-holland
    • Rotterdam, Zuid-holland, Netherlands, 3079 DZ
      • Maasstad Ziekenhuis
• Poland
  • Kujawsko-pomorskie, Poland, 87-800
    • SPZOZ, Szpital Wojewódzki we Wloclawku
  • Poznan, Poland, 61-848
    • Samodzielny Publiczny Szpital Kliniczny nr. 1 im. Przemienienia Panskiego
  • Torun, Poland, 87-100
    • Wojewódzki Szpital Zespolony im. Ludwika Rydygiera w Toruniu
  • Warszawa, Poland, 02-097
    • SPZOZ, Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-981
      • 4th Wojskowy Szpital Kliniczny z Poliklinika, Klinika Kardiologii
  • Lodzkie
    • Belchatów, Lodzkie, Poland, 97-400
      • American Heart of Poland S.A.
  • Malopolskie
    • Chrzanów, Malopolskie, Poland, 32-500
      • American Heart of Poland S.A.
    • Kraków, Malopolskie, Poland, 31-501
      • Szpital Uniwersytecki w Krakowie
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-507
      • Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie
    • Warszawa, Mazowieckie, Poland, 04-628
      • Instytut Kardiologii
  • Opolskie
    • Kedzierzyn Kozle, Opolskie, Poland, 47-200
      • American Heart of Poland S.A.
  • Podkarpackie
    • Mielec, Podkarpackie, Poland, 39-300
      • American Heart of Poland S.A.
  • Slaskie
    • Bielsko-Biala, Slaskie, Poland, 43-316
      • American Heart of Poland S.A.
    • Dabrowa Górnicza, Slaskie, Poland, 41-300
      • American Heart of Poland S.A.
    • Katowice, Slaskie, Poland, 40-635
      • SPZOZ, SPSK nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach, Górnoslaskie Centrum Medyczne
    • Tychy, Slaskie, Poland, 43-100
      • American Heart of Poland S.A.
    • Ustron, Slaskie, Poland, 43-450
      • American Heart of Poland S.A.
• Russian Federation
  • Barnaul, Russian Federation, 656055
    • Altai Regional Cardiological Dispensary
  • Chelyabinsk, Russian Federation, 454021
    • Regional Clinical Hospital №3
  • Ekaterinburg, Russian Federation, 620144
    • Ural Institute of Cardiology
  • Ivanovo, Russian Federation, 153012
    • Cardiological dispensary
  • Kazan, Russian Federation, 420043
    • Republic Clinical Hospital № 2
  • Kemerovo, Russian Federation, 650002
    • Research Institute for Complex Issues of Cardiovascular Diseases
  • Kirovsk, Leningradskaya Region, Russian Federation, 187342
    • Medical Center "Alliance"
  • Krasnoyarsk, Russian Federation, 660022
    • Regional Clinical Hospital
  • Moscow, Russian Federation, 111539
    • City Clinical Hospital #15 named after O.M. Filatov
  • Moscow, Russian Federation, 101990
    • National Research Center for Preventive Medicine
  • Moscow, Russian Federation, 125284
    • City clinical hospital n.a. S.P.Botkin
  • Moscow, Russian Federation, 109240
    • City Clinical Hospital # 23 n.a."Medsantrud"
  • Moscow, Russian Federation, 119991
    • University Clinical Hospital #1
  • Nizhni Novgorod, Russian Federation, 603005
    • City Clinical Hospital #5
  • Novosibirsk, Russian Federation, 630008
    • City Clinical Emergency Hospital # 2
  • Penza, Russian Federation, 444026
    • Penza Regional Clinical Hospital n.a. N.N. Burdenko
  • Saint-Petersburg, Russian Federation, 197341
    • Federal Center of Heart, Blood and Endocrinology n.a. V.A.Almazov
  • Tomsk, Russian Federation, 634012
    • Scientific and Research Institution Of Cardiology
  • Volgograd, Russian Federation, 400008
    • Volgograd Regional Clinical Cardiological Center
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Vall d´hebron
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Malaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Hospital Central de Asturias
  • Barcelona
    • L´Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36214
      • Complejo Hospitalario Universitario de Vigo, Meixoeiro Hospital
• Sweden
  • Falun, Sweden, 791 82
    • Falu Lasarett
  • Göteborg, Sweden, 413 45
    • Sahlgrenska Universitetsjukhuset
  • Karlstad, Sweden, 65185
    • Karlstad Central Hospital
  • Uppsala, Sweden, 75185
    • Uppsala University Hospital
  • Orebro
    • Örebro, Orebro, Sweden, 701 85
      • Universitetssjukhuset Örebro
• United Kingdom
  • Northern Ireland, United Kingdom, BT12 6BA
    • Royal Victoria Hospital
  • England
    • Brighton, England, United Kingdom, BN2 5BE
      • Royal Sussex County Hospital
    • Middlesbrough, England, United Kingdom, TS4 3BW
      • The James Cook University Hospital
    • Newcastle Upon Tyne, England, United Kingdom, NE7 7DN
      • Freeman Hospital
    • Surrey, England, United Kingdom, KT16 0PZ
      • Ashford and Saint Peter's Hospital NHS Trust
    • West Sussex, England, United Kingdom, PO19 6SE
      • Saint Richards Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35211
      • Cardiology, PC
    • Huntsville, Alabama, United States, 35801
      • Heart Center Research, LLC
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Healthcare
    • Scottsdale, Arizona, United States, 85251
      • Scottsdale Healthcare
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego
    • Moreno Valley, California, United States, 92553
      • Spectrum Clinical Research Institute, Inc
    • San Diego, California, United States, 92161
      • Veterans Affairs San Diego Healthcare System
    • Walnut Creek, California, United States, 94598
      • John Muir Medical Center Concord Campus
  • Colorado
    • Littleton, Colorado, United States, 80120
      • South Denver Cardiology Associates, PC
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
    • Stamford, Connecticut, United States, 06905
      • Cardiology Associates of Fairfield County, PC
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Atlantis, Florida, United States, 33462
      • Zasa Clinical Research
    • Daytona Beach, Florida, United States, 32117
      • Cardiology Research Associates
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Hialeah, Florida, United States, 33010
      • Michigan Heart, PC
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Jacksonville, Florida, United States, 32216
      • East Coast Institute for Research
    • Jacksonville, Florida, United States, 32207
      • Jacksonville Heart Center
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Sciences Center-Jacksonville
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Orlando, Florida, United States, 32803
      • Florida Heart Institute
    • Panama City, Florida, United States, 32401
      • Cardiovascular Institute of Northwest Florida
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Research Institute
    • Tampa, Florida, United States, 33613
      • Pepin Heart Hospital and Dr. Kiran C. Patel Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Jerseyville, Illinois, United States, 62052
      • Gateway Cardiology, PC
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • The Indiana Heart Hospital
    • Indianapolis, Indiana, United States, 46237
      • Indiana Heart Physicians, Inc.
    • Valparaiso, Indiana, United States, 46383
      • Northwest Indiana Cardiovascular Physicians
  • Iowa
    • West De Moines, Iowa, United States, 50266
      • Iowa Heart Center
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Saint Joseph Cardiology Associates
  • Louisiana
    • Minden, Louisiana, United States, 71055
      • Clinical Trials of America, Inc.
    • Shreveport, Louisiana, United States, 71103
      • Clinical Trials of America, Inc.
  • Maine
    • Bangor, Maine, United States, 04401
      • Northeast Cardiology Associates
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Union Memorial Hospital
    • Baltimore, Maryland, United States, 21215
      • Baltimore Heart Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02135
      • Saint Elizabeth's Medical Center
    • Hyannis, Massachusetts, United States, 02601
      • Cape Cod Research Institute
  • Michigan
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital and Medical Center
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essentia Health
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
    • Saint Cloud, Minnesota, United States, 56303
      • Saint Cloud Hospital
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Cardiology Associates of North Mississippi
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Gateway Cardiology, PC
    • Springfield, Missouri, United States, 65804
      • Saint John's Regional Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • Buffalo, New York, United States, 14215
      • Buffalo Heart group
    • Liverpool, New York, United States, 13088
      • SJH Cardiology Associates
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Poughkeepsie, New York, United States, 12601
      • Hudson Valley Heart Center
    • Stony Brook, New York, United States, 11790
      • Stony Brook University Medical Center
    • Utica, New York, United States, 13501
      • Central New York Cardiology
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center
    • Williamsville, New York, United States, 14221
      • Buffalo Cardiology and Pulmonary Associates, PC
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Cardiology Associates
    • Charlotte, North Carolina, United States, 28204
      • Mid Carolina Cardiology
    • Durham, North Carolina, United States, 27705
      • Veterans Affairs Medical Center, Duke University Medical Center
    • High Point, North Carolina, United States, 27262
      • Carolina Cardiology Associates
    • Raleigh, North Carolina, United States, 27610
      • Wake Heart Research
  • Ohio
    • Columbus, Ohio, United States, 43214
      • Ohio Health Research Institute
    • Zanesville, Ohio, United States, 43701
      • Cardiology Associates of Southeast Ohio, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73135
      • South Oklahoma Heart Research
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma City Veterans' Affairs Medical Center
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • The Heart and Vascular Center
    • Doylestown, Pennsylvania, United States, 18901
      • Central Bucks Cardiology
    • Erie, Pennsylvania, United States, 16502
      • Saint Vincent Health Care Center
    • Pittsburgh, Pennsylvania, United States, 15240
      • Veterans Administration Medical Center
    • Wormleysburg, Pennsylvania, United States, 17043
      • Pinnacle Health System
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Jackson, Tennessee, United States, 38301
      • Research Associates Of Jackson
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee
    • Nashville, Tennessee, United States, 37203
      • Centennial Heart Cardiovascular Consultants, LLC
  • Texas
    • Dallas, Texas, United States, 75216
      • North Texas Healthcare System, Dept. of Veteran's Affairs
    • Humble, Texas, United States, 77338
      • Humble Cardiology Associates
    • Mission, Texas, United States, 78572
      • Gamma Medical Research Inc.
    • San Antonio, Texas, United States, 78258
      • San Antonio Endovascular and Heart Institute
    • Victoria, Texas, United States, 77901
      • Victoria Heart and Vascular Center
  • Utah
    • Layton, Utah, United States, 84041
      • Utah Cardiology, PC
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center, Fletcher Allen Health Care
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Cardiovascular Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent
2. Males and females aged 18 years and older
3. History of chronic angina defined as at least 2 episodes of anginal pain or discomfort in the chest, jaw, shoulder, back, neck, or arm that is precipitated by exertion or emotional stress, and relieved by rest or sublingual nitroglycerin, which occurred on at least 2 separate days and at least 14 days prior to PCI (in the case of staged PCI procedures, at least 14 days prior to the first PCI in the series). Participants may or may not have additional angina episodes within the 14 days prior to their first PCI in the series, as well as any time prior to Randomization.

4. PCI for any indication (ACS or non-ACS). For the purposes of stratification at randomization, ACS will be defined as hospitalization for anginal pain or discomfort within the previous 24 hours to their hospitalization with any one (or more) of the following criteria:

   i. Elevated troponin or creatinine kinase-MB (CK-MB) consistent with myocardial infarction (MI), as reported by local laboratory and measured prior to index PCI ii. Electrocardiographic changes (including transient changes) comprising new or presumably new ST segment depression ≥ 0.1 mV (≥ 1 mm), or ST segment elevation ≥ 0.1 mV (≥ 1 mm) in at least 2 contiguous leads, or new or presumably new Left Bundle Branch Block

5. Randomization within 14 days post-PCI. In the case of staged PCI procedures, randomization has to occur within 14 days of the last PCI in the series. Participants may be randomized starting on the day of PCI and anytime during the following 14 days. PCI is defined as an attempt to cross the lesion with a wire with the intention of performing revascularization.
6. Post-PCI (post the last PCI for staged procedures) evidence of incomplete revascularization defined as the presence of one or more visually estimated ≥ 50% stenoses in one or more coronary arteries with reference vessel diameter of at least 2.0 mm, whether in the target vessel or in a non-target vessel regardless of the presence or absence of coronary collaterals. In the case of a participant post-coronary artery bypass grafting (CABG), incomplete revascularization is defined as the presence of one or more visually estimated ≥ 50% stenoses in an unbypassed epicardial vessel with a reference diameter of ≥ 2.0 mm, or one or more visually estimated ≥ 50% stenoses in a bypass graft supplying an otherwise unrevascularized myocardial territory.

7. Clinically stable post-PCI. Participants randomized in-hospital on day of planned discharge or in clinic are considered stable. Participants randomized in-hospital prior to day of planned discharge must meet all of the following criteria:

   i. CK-MB < 3 times the upper limit of normal (ULN) at least 3 hours post-PCI, or if ≥ 3 times the ULN with evidence of decreasing CK-MB (decreased by at least 20% from the prior measurement) as reported by local laboratory. If CK-MB is not available, a participant must have evidence of normal or decreasing troponin levels (by at least 20% from the prior measurement) at least 3 hours post-PCI, as reported by local laboratory.

   ii. Systolic blood pressure ≥ 90 mm Hg and not receiving pressors or inotropes iii. No current requirement for an intra-aortic balloon pump (IABP) or any left ventricular assist device iv. No current requirement for intravenous (IV) nitroglycerin

8. Ability and willingness to comply with all study procedures during the course of the study
9. Females of childbearing potential must have a negative pregnancy test at Screening (unless surgically sterile or post-menopausal) and must agree to use highly effective contraception methods from Screening throughout the duration of study treatment and for 14 days following the last dose of study drug.

Exclusion Criteria:

1. Any future planned revascularization (including staged procedures) or possible planned revascularization (ie, planned stress test to assess the imminent need for additional revascularization). Future planned stress tests for purposes of monitoring are permitted but strongly discouraged. Participants may be enrolled after the last PCI in the staged series or once a decision is made not to perform a follow up PCI, as long as Randomization occurs within 14 days from the last PCI. If a participant has had a stress test post-PCI and prior to Randomization and no further intervention is planned, the participant may be enrolled within 14 days from the last PCI.
2. Unrevascularized left main coronary artery stenosis ≥ 50%. Participants with a history of CABG to the left coronary system will be considered to have a revascularized left main if at least one graft is patent.

3. Major complication during or after the index PCI (in the case of staged PCI, the last in the series) including:

   i. Major bleeding (TIMI Bleeding classification or any bleeding requiring blood transfusion of ≥ 2 units of red blood cells) ii. Coronary perforation requiring treatment iii. Procedural complication requiring surgery (including CABG or peripheral vascular surgery)

4. Stroke within 90 days prior to Randomization, or any history of stroke with permanent major neurologic disability (eg, aphasia or significant motor dysfunction)
5. Cardiogenic shock within 90 days prior to Randomization (transient decreases in blood pressure without clinical sequelae are not considered to be cardiogenic shock)
6. New York Heart Association (NYHA) Class III or IV heart failure
7. Severe renal insufficiency as assessed by an estimated glomerular filtration rate < 30 mL/min/1.73m2 using the 4 variable modification of diet in renal disease (MDRD) equation per local laboratory (based on the last available measurement prior to Randomization, collected within 1 month prior to the index PCI [in the case of staged PCI, the last in the series])
8. Liver cirrhosis
9. Use of Class Ia, Ic, or Class III antiarrhythmics, except for amiodarone
10. Current treatment with strong inhibitors of CYP3A
11. Current treatment with CYP3A4 inducers or P-gp inducers
12. Participants taking > 20 mg simvastatin daily or > 40 mg lovastatin daily who cannot reduce the dose to 20 mg once daily for simvastatin or 40 mg once daily for lovastatin, or who cannot switch to another statin
13. Participants taking greater than a total of 1000 mg daily of metformin who cannot reduce the dose to a maximum total of 1000 mg daily (additional anti-diabetic medications may be added as clinically indicated to allow participants to decrease their metformin dose and maintain glycemic control)
14. Previous treatment with ranolazine for > 7 consecutive days within 30 days prior to Randomization, or known hypersensitivity or intolerance to ranolazine or to any of the excipients
15. Participation in another investigational drug or investigational device study within 30 days prior to Randomization (participation in registries is allowed)
16. Women who are pregnant or breast feeding
17. Non-coronary artery disease comorbid conditions (eg, advanced malignancy, severe aortic stenosis) which are likely to result in death within 2 years of Randomization
18. Any condition that in the opinion of the investigator would preclude compliance with the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Subjects will receive one tablet of matching placebo twice daily for 7 days, followed by two tablets of matching placebo twice daily for the duration of the study. Subjects receiving a moderate CYP3A4 inhibitor will receive ranolazine 500 mg or placebo administered orally twice a day for the duration of the concomitant therapy.
EXPERIMENTAL: Ranolazine	Drug: Ranolazine; Subjects will receive ranolazine 500 milligrams (mg) twice daily for 7 days, followed by 1000 mg administered orally twice daily for the duration of the study. Subjects receiving a moderate CYP3A4 inhibitor will receive ranolazine 500 mg or placebo administered orally twice a day for the duration of the concomitant therapy.; Other Names: Ranexa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan-Meier Estimates for Time From Randomization to First Occurrence of Ischemia-driven Revascularization or Ischemia-driven Hospitalization Without Revascularization	Time to event distributions were estimated by the Kaplan-Meier (KM) method. 1 month = 28 days; 1 calendar year = 365 days.	Baseline through end of study (average 90 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan-Meier Estimates for Time From Randomization to Sudden Cardiac Death	Time to event distributions were estimated by the Kaplan-Meier method. 1 month = 28 days; 1 calendar year = 365 days.	Baseline through end of study (average 90 weeks)
Kaplan-Meier Estimates for Time From Randomization to Cardiovascular Death	Time to event distributions were estimated by the Kaplan-Meier method. 1 month = 28 days; 1 calendar year = 365 days.	Baseline through end of study (average 90 weeks)
Kaplan-Meier Estimates for Time From Randomization to Myocardial Infarction	Time to event distributions were estimated by the Kaplan-Meier method. 1 month = 28 days; 1 calendar year = 365 days.	Baseline through end of study (average 90 weeks)

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Weisz G, Farzaneh-Far R, Ben-Yehuda O, Debruyne B, Montalescot G, Lerman A, Mahmud E, Alexander KP, Ohman EM, White HD, Olmsted A, Walker GA, Stone GW. Use of ranolazine in patients with incomplete revascularization after percutaneous coronary intervention: design and rationale of the Ranolazine for Incomplete Vessel Revascularization Post-Percutaneous Coronary Intervention (RIVER-PCI) trial. Am Heart J. 2013 Dec;166(6):953-959.e3. doi: 10.1016/j.ahj.2013.08.004. Epub 2013 Oct 16.
• Weisz G, Genereux P, Iniguez A, Zurakowski A, Shechter M, Alexander KP, Dressler O, Osmukhina A, James S, Ohman EM, Ben-Yehuda O, Farzaneh-Far R, Stone GW; RIVER-PCI investigators. Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2016 Jan 9;387(10014):136-45. doi: 10.1016/S0140-6736(15)00459-6. Epub 2015 Oct 22.
• Alexander KP, Weisz G, Prather K, James S, Mark DB, Anstrom KJ, Davidson-Ray L, Witkowski A, Mulkay AJ, Osmukhina A, Farzaneh-Far R, Ben-Yehuda O, Stone GW, Ohman EM. Effects of Ranolazine on Angina and Quality of Life After Percutaneous Coronary Intervention With Incomplete Revascularization: Results From the Ranolazine for Incomplete Vessel Revascularization (RIVER-PCI) Trial. Circulation. 2016 Jan 5;133(1):39-47. doi: 10.1161/CIRCULATIONAHA.115.019768. Epub 2015 Nov 10.
• Fanaroff AC, Prather K, Brucker A, Wojdyla D, Davidson-Ray L, Mark DB, Williams RB, Barefoot J, Weisz G, Ben-Yehuda O, Stone GW, Ohman EM, Alexander KP. Relationship Between Optimism and Outcomes in Patients With Chronic Angina Pectoris. Am J Cardiol. 2019 May 1;123(9):1399-1405. doi: 10.1016/j.amjcard.2019.01.036. Epub 2019 Feb 7.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: September 22, 2011
• First Submitted That Met QC Criteria: September 27, 2011
• First Posted (ESTIMATE): September 28, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): July 15, 2016
• Last Update Submitted That Met QC Criteria: June 6, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Coronary Disease; Chest Pain; Coronary Artery Disease; Angina Pectoris; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Sodium Channel Blockers; Ranolazine
• Other Study ID Numbers: GS-US-259-0116; 2011-002507-15 (EUDRACT_NUMBER)