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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01471522
Other study ID # 11-00498
Secondary ID 1U01HL105907
Status Completed
Phase N/A
First received
Last updated
Start date July 2012
Est. completion date May 30, 2023

Study information

Verified date May 2023
Source NYU Langone Health
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of the ISCHEMIA trial is to determine the best management strategy for higher-risk patients with stable ischemic heart disease (SIHD). This is a multicenter randomized controlled trial with 5179 randomized participants with moderate or severe ischemia on stress testing. A blinded coronary computed tomography angiogram (CCTA) was performed in most participants with eGFR ≥60 mL/min/1.73m2 to identify and exclude participants with either significant unprotected left main disease (≥50% stenosis) or those without obstructive CAD (<50% stenosis in all major coronary arteries). Of 8518 participants enrolled, those that had insufficient ischemia, ineligible anatomy demonstrated on CCTA or another exclusion criterion, did not go on to randomization. Eligible participants were then assigned at random to a routine invasive strategy (INV) with cardiac catheterization followed by revascularization, if feasible, plus optimal medical therapy (OMT) or to a conservative strategy (CON) of OMT, with cardiac catheterization and revascularization reserved for those who fail OMT. SPECIFIC AIMS A. Primary Aim The primary aim of the ISCHEMIA trial is to determine whether an initial invasive strategy of cardiac catheterization followed by optimal revascularization, if feasible, in addition to OMT, will reduce the primary composite endpoint of cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure in participants with SIHD and moderate or severe ischemia over an average follow-up of approximately 3.5 years compared with an initial conservative strategy of OMT alone with catheterization reserved for failure of OMT. B. Secondary Aims Secondary aims are to determine whether an initial invasive strategy compared to a conservative strategy will improve: 1) the composite of CV death or MI; 2) angina symptoms and quality of life, as assessed by the Seattle Angina Questionnaire; 3) all-cause mortality; 4) net clinical benefit assessed by including stroke in the primary and secondary composite endpoints; and 5) individual components of the composite endpoints. Condition: Coronary Disease Procedure: Coronary CT Angiogram Procedure: Cardiac catheterization Phase: Phase III per NIH Condition: Cardiovascular Diseases Procedure: Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions Phase: Phase III per NIH Condition: Heart Diseases Procedure: Coronary Artery Bypass Surgery Phase: Phase III per NIH


Description:

BACKGROUND: Evidence supporting a routine invasive practice paradigm for patients with SIHD is outdated. In strategy trials conducted in the 1970s, coronary artery bypass grafting (CABG) improved survival as compared with no CABG in SIHD patients with high-risk anatomic features. The relevance of these studies today is speculative because contemporary secondary prevention-aspirin, beta-blockers, statins, ACE inhibitors, and lifestyle interventions-were used minimally if at all. Subsequent trials have compared percutaneous coronary intervention (PCI) with medical therapy, as PCI has replaced CABG as the dominant method of revascularization for SIHD. To date, PCI has not been shown to reduce death or myocardial infarction (MI) compared with medical therapy in SIHD patients. COURAGE and BARI 2D, the two largest trials comparing coronary revascularization vs. medical therapy in SIHD patients, found that among patients selected on the basis of coronary anatomy after cardiac catheterization, an initial management strategy of coronary revascularization (PCI, PCI or CABG, respectively) did not reduce the primary endpoints of death or MI (COURAGE), or death (BARI 2D) compared with OMT alone. These data suggest, but do not prove, that routine cardiac catheterization--which often leads to ad hoc PCI through the diagnostic-therapeutic cascade--may not be required in SIHD patients. However, most patients enrolled in COURAGE and BARI 2D who had ischemia severity documented at baseline had only mild or moderate ischemia, leaving open the question of the appropriate role of cardiac catheterization and revascularization among higher-risk patients with more severe ischemia. Observational data suggest that revascularization of patients with moderate-to-severe ischemia is associated with a lower mortality than medical therapy alone, but such data cannot establish a cause and effect relationship. In clinical practice only about half such patients are referred for cardiac catheterization, indicating equipoise. Furthermore, analysis of outcomes for 468 COURAGE patients with moderate-to-severe ischemia at baseline did not reveal a benefit from PCI. This issue cannot be resolved using available data because all prior SIHD strategy trials enrolled patients after cardiac catheterization, introducing undefined selection biases (e.g., highest risk patients not enrolled) and making translation of study results problematic for clinicians managing patients who have not yet had cardiac catheterization. A clinical trial in SIHD patients uniformly at higher risk (which could not have been performed before COURAGE and BARI 2D results were available) is needed to inform optimal management for such patients. DESIGN NARRATIVE, INCLUDING MODIFICATIONS DURING THE TRIAL Primary Endpoint A composite of CV death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure was proposed as the primary endpoint in the application that was funded by NLHBI, with a secondary endpoint of CV death or MI. Study protocol version 1.0 was finalized on January 18, 2012 after review and approval by the protocol review committee (DSMB) with the primary endpoint specified as the composite of CV death or MI. Regarding the final status of the primary endpoint, the protocol stated: "To ensure that the primary analysis is well-powered and useful, a prospective plan to allow extending follow-up and/or changing the primary endpoint based on aggregate event rate data will be established prior to the first review of unblinded trial data. At a designated time during the trial, an analysis will be conducted to estimate the overall aggregate primary endpoint event rate and project the final number of observed events. If the estimated unconditional power (i.e. based on aggregate event rate data; not by treatment group) is less than the originally targeted 90%, then one or more of the following options will be considered: 1. Extend follow-up to allow more events to accrue. 2. Change the primary endpoint to one that occurs more frequently. The current primary endpoint would become a secondary endpoint. The proposed new primary endpoint would be the composite of CV death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure. 3. Follow the recommendation of an independent advisory panel. An independent advisory panel, separate from the DSMB, will be convened for the purpose of reviewing unconditional power estimates and making a recommendation to the NHLBI Director. Members of this panel will not have access to unblinded data by treatment group or other data that may bias their recommendation." All 5 event types were adjudicated throughout the trial. Study protocol v2.0 (January 2014) allowed ischemia eligibility by non-imaging exercise stress test if more stringent (≥70% stenosis) CCTA criteria were met. The 2016 protocol addendum describes the NHLBI-approved reduction in sample size and extension of recruitment and follow-up due to slower than projected recruitment. The pre-specified first analysis for monitoring and projecting the final aggregate number of primary endpoint events was conducted in 2015. In 2016, the projected need to increase the power by extending follow-up and elevating the 5-component secondary endpoint to become primary was discussed at Steering Committee and Investigator meetings and communicated by email. An Independent Advisory Panel convened by NHLBI met in May 2017, and in June 2017 NHLBI approved the Independent Advisory Panel's recommendation to elevate the 5-component secondary endpoint to become primary and retain the 2-component composite as a key secondary endpoint. The panel also recommended extension of follow-up. This was communicated to the Steering Committee and Investigators at August and November 2017 meetings and by email. The last visit date was June 30, 2019. A statistical plan developed for the Independent Advisory Panel process in 2012 specified that a decision about changing the primary endpoint would be targeted to occur before 75% of the final number of primary endpoint events had accrued. Although the final number of primary endpoint events was unknown during the course of the trial, estimates performed at the time of the Advisory Panel meeting suggested that the ratio of accrued endpoint events to final endpoint events was below 50%. See Maron DJ et al. Am Heart J. 2018 201:124-135. PMC6005768 for additional details about modifications to the trial while it was being conducted. Analysis of Patients' Health Status as a Key Secondary Endpoint A key secondary objective of the ISCHEMIA trial is to compare the quality of life outcomes-patients' symptoms, functioning and well-being-between those assigned to an invasive strategy as compared with a conservative strategy. In the protocol, angina frequency and disease-specific quality of life measured by the Seattle Angina Questionnaire (SAQ) Angina Frequency and Quality of Life scales, respectively, are described as the tools that will be used to make this comparative assessment. Recent work has indicated that it is possible to combine the information from the individual domain scores in the SAQ into a new Summary Score that captures the information from the SAQ Angina Frequency, Physical Limitation and Quality of Life scales into a single overall score. The advantages of using a summary score as the primary measure of QOL effects of a therapy are a single primary endpoint comparison rather than two or three (eliminating concerns some may have about multiple comparisons) and a more intuitive holistic (patient-centric) interpretation of the effectiveness results. With these advantages in mind, the ISCHEMIA leadership has agreed that the SAQ Summary Score will be designated as the primary way this outcome for this key secondary endpoint of the ISCHEMIA trial will be analyzed and interpreted, with the individual SAQ scores being used in a secondary, explanatory and descriptive role. PARTICIPATING COUNTRIES: North America: Canada; Mexico; USA South America: Argentina; Brazil; Peru Asia: China; India; Japan; Malaysia; Singapore; Taiwan; Thailand; Russian Federation Pacifica: Australia; New Zealand Europe: Austria; Belgium; France; Germany; Hungary; Italy; Lithuania; Macedonia; Netherlands; Poland; Portugal; Romania; Serbia; Spain; Sweden; Switzerland; UK Middle East: Egypt; Israel; Saudi Arabia Africa: South Africa


Recruitment information / eligibility

Status Completed
Enrollment 5179
Est. completion date May 30, 2023
Est. primary completion date June 30, 2019
Accepts healthy volunteers No
Gender All
Age group 21 Years and older
Eligibility Inclusion Criteria: - At least moderate ischemia on a qualifying stress test - Participant is willing to comply with all aspects of the protocol, including adherence to the assigned strategy, medical therapy and follow-up visits - Participant is willing to give written informed consent - Age = 21 years Exclusion Criteria: - LVEF < 35% - History of unprotected left main stenosis >50% on prior coronary computed tomography angiography (CCTA) or prior cardiac catheterization (if available) - Finding of "no obstructive CAD" (<50% stenosis in all major epicardial vessels) on prior CCTA or prior catheterization, performed within 12 months - Coronary anatomy unsuitable for either PCI or CABG - Unacceptable level of angina despite maximal medical therapy - Very dissatisfied with medical management of angina - History of noncompliance with medical therapy - Acute coronary syndrome within the previous 2 months - PCI within the previous 12 months - Stroke within the previous 6 months or spontaneous intracranial hemorrhage at any time - History of ventricular tachycardia requiring therapy for termination, or symptomatic sustained ventricular tachycardia not due to a transient reversible cause - NYHA class III-IV heart failure at entry or hospitalization for exacerbation of chronic heart failure within the previous 6 months - Non-ischemic dilated or hypertrophic cardiomyopathy - End stage renal disease on dialysis or estimated glomerular filtration rate (eGFR) <30mL/min (not an exclusion criterion for CKD ancillary trial, see CKD ancillary trial, Section 18) - Severe valvular disease or valvular disease likely to require surgery or percutaneous valve replacement during the trial - Allergy to radiographic contrast that cannot be adequately pre-medicated, or any prior anaphylaxis to radiographic contrast - Planned major surgery necessitating interruption of dual antiplatelet therapy (note that patients may be eligible after planned surgery) - Life expectancy less than the duration of the trial due to non-cardiovascular comorbidity - Pregnancy (known to be pregnant; to be confirmed before CCTA and/or randomization, if applicable) - Patient who, in the judgment of the patient's physician, is likely to have significant unprotected left main stenosis (Those who are able to undergo CCTA will have visual assessment of the left main coronary artery by the CCTA core lab) - Enrolled in a competing trial that involves a non-approved cardiac drug or device - Inability to comply with the protocol - Exceeds the weight or size limit for CCTA or cardiac catheterization at the site - Canadian Cardiovascular Society Class III angina of recent onset, OR angina of any class with a rapidly progressive or accelerating pattern - Canadian Cardiovascular Society Class IV angina, including unprovoked rest angina - High risk of bleeding which would contraindicate the use of dual antiplatelet therapy - Cardiac transplant recipient - Prior CABG, unless CABG was performed more than 12 months ago, and coronary anatomy has been demonstrated to be suitable for PCI or repeat CABG to accomplish complete revascularization of ischemic areas (CCC approval required)

Study Design


Intervention

Procedure:
cardiac catheterization
Narrowed blood vessels can be opened without surgery using stents or can be bypassed with surgery. To determine which is the best approach for you the doctor needs to look at your blood vessels to see where the narrowings are and how much narrowing there is. This is done by a procedure known as a cardiac catheterization.
coronary artery bypass graft surgery
Artery narrowing is bypassed during surgery with a healthy artery or vein from another part of the body. This is known as coronary artery bypass grafting, or CABG (said, "cabbage"). The surgery creates new routes around narrowed and blocked heart arteries. This allows more blood flow to the heart.
percutaneous coronary intervention
Percutaneous coronary intervention may be done as part of the cardiac catheterization procedure. With this procedure a small, hollow, mesh tube (stent) is inserted into the narrowed part of the artery. The stent pushes the plaque against the artery wall, and opens the vessel to allow better blood flow.
Behavioral:
Lifestyle
diet, physical activity, smoking cessation
Drug:
Medication
antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies

Locations

Country Name City State
Argentina Hospital Italiano Regional del Sur Bahia Blanca Bahia Blanca Buenos Aires
Argentina Fundacion Favaloro Ciudad Autonoma de Buenos Aires Buenos Aires
Argentina Clinica Del Prado Cordoba
Argentina Clínica Privada Vélez Sarsfield Cordoba
Argentina Clinica Romagosa and Clinica De La Familia Cordoba
Argentina Instituto Medico DAMIC Cordoba CBA
Australia Flinders Medical Centre Adelaide South Australia
Australia John Hunter Hospital New Lambton Heights New South Wales
Australia Royal Perth Hospital Perth Western Australia
Australia The Queen Elizabeth Hospital Woodville South South Australia
Austria LKH Graz West Austria Graz Stmk
Austria Medical University of Vienna, Department of Cardiology Vienna Wien
Austria Wilhelminen Hospital Vienna Vienna Wien
Belgium University Hospital Leuven Leuven Brabant
Brazil Hospital Lifecenter Belo Horizonte Minas Gerais
Brazil Hospital Pró-Cardíaco Botafogo Rio De Janeiro
Brazil Hospital Cardiologico Costantini Curitiba Parana
Brazil Quanta Diagnostico & Terapia Curitiba Parana
Brazil Hospital Sao Vicente de Paulo Fundo RS
Brazil Instituto Dante Pazzanese de Cardiologia Ibirapuera Sao Paulo
Brazil Hospital Maternidade e Pronto Socorro Santa Lucia Pocos de Caldas Minas Gerais
Brazil Hospital de Clinicas de Porto Alegre Porto Alegre RS
Brazil Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sol Porto Alegre Rio Grande Do Sul
Brazil Instituto de Cardiologia de Porto Alegre Porto Alegre Rio Grande Do Sul
Brazil Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo Ribeirao Preto Sao Paulo
Brazil Fundacao Bahiana de Cardilogia Salvador Bahia
Brazil Hospital da Bahia Salvador
Brazil Heart Institute (InCor) University of São Paulo Sao Paulo
Brazil Hospital Celso Pierro Sao Paulo
Brazil Hospital TotalCor Sao Paulo SP
Brazil Unifesp - Hospital Sao Paulo Sao Paulo
Canada University of Calgary Calgary Alberta
Canada University of Alberta Edmonton Alberta
Canada West Lincoln Memorial Hospital Grimsby Ontario
Canada Hamilton General Hospital Hamilton Ontario
Canada London Health Sciences Centre London Ontario
Canada Dixie Medical Group Mississauga Ontario
Canada Montreal Heart Institute Montreal Quebec
Canada Centre Intégré Universitaire de Santé et de Services Sociaux du Montréal Montréal Quebec
Canada Dr. James Cha Oshawa Ontario
Canada University of Ottawa Heart Institute Ottawa
Canada Scarborough Cardiology Research Scarborough Ontario
Canada Saint Catharines General Hospital St. Catharines Ontario
Canada CISSSL - Hopital Pierre-Le Gardeur Terrebonne Quebec
Canada St. Michael's Hospital Toronto Ontario
Canada University Health Network Toronto Ontario
Canada Women's College Hospital Toronto Ontario
Canada Centre Hospitalier de Regional Trois-Rivieres Trois-Rivieres Quebec
Canada Vancouver General Hospital Vancouver British Columbia
Canada Northwest GTA Cardiovascular and Heart Rhythm Program Vaughan Ontario
China Beijing Anzhen Hospital Beijing Chaoyang
China Beijing Chao-yang Hospital, Capital Medical University Beijing Beijing
China Chinese Academy of Medical Sciences, Fuwai Hospital Beijing Beijing
China Liangxiang Hospital, Beijing Fangshan District Beijing Fangshan
China Peking Union Medical College Hospital Beijing Beijing
China Affiliated Zhongshan Hospital of Dalian University Dalian Liaoning
China Guangdong General Hospital Guangzhou Guangdong
China The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang
China Affiliated Hospital of Jining Medical University Jining Shandong
China Qingdao Fuwai Hospital Qingdao Shandong
China Shanxi Cardiovascular Hospital Taiyuan Shanxi
China Tangshan Gongren Hospital Tangshan Hebei
China TEDA International Cardiovascular Hospital Tianjing Tianjing
China First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang
China Tongji Medical College Wuhan Hubei
China Wuhan Asia Heart Hospital Wuhan Hubei
China Wuhan Union Hospital, Tongji Medical College, Huazhong Science and Tech University Wuhan Hubei
China Shanxi Provincial People's Hospital Xian Shanxi
China The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan
China The Second Affiliated Hospital of Zhengzhou University Zhengzhou Henan
Egypt Cairo University Cairo
France Centre Hospitalier Universitaire d'Angers Angers Cedex 9 Pays De La Loire
France Ambroise Pare Hospital Boulogne Ile De France
France C.H. Louis Pasteur Chatres Centre
France Antoine-Beclere Hospital Clamart Cedex Ile-de-France
France Centre Hospitalier Sud Francilien Corbeil-Essonnes cedex Ile De France
France Grenoble University Hospital Grenoble Isere
France Bichat Hospital Paris Ile-de-France
Germany Universitatsklinikum Bonn Bonn NRW
Germany Praxisklinik Herz Und Gefaesse Dresden Saxony
Germany University Hospital Jena Jena Thuringia
Germany Robert-Bosch-Krankenhaus Stuttgart BW
Hungary Eszszk- Szent Istvan Hospital Budapest
Hungary George Gottsegen National Institute of Cardiology Budapest
Hungary Heart and Vascular Center, Semmelweis University Budapest
Hungary Military Hospital, Budapest Budapest
Hungary University of Szeged Szeged Szeged Megyei Varos
India Sri Jayadeva Institute of Cardiovascular Sciences and Research Bangalore Karnataka
India Government Medical College Calicut Kerala
India Apollo Research and Innovation Chennai Tamil Nadu
India Apollo Research & Innovations Hyderabad Telangana
India CARE Hospital Hyderabad Andhra Pradesh
India CARE Nampally Hyderabad Telangana
India Gurunanak CARE Hospital Hyderabad AP
India MOSC Medical College Hospital, Kolenchery Kolenchery Kerala
India King George's Medical University, Department of Cardiology Lucknow Uttar Pradesh
India Hero DMC Heart Institute, Dayanand Medical College and Hospital Ludhiana Punjab
India All India Institute of Medical Sciences New Delhi
India Batra Hospital and Medical Research Centre (BHMRC) New Delhi Delhi
India Dr Ram Manohar Lohia Hospital New Delhi Delhi
India Fortis Escort Heart Institute New Delhi Delhi
India Fortis Healthcare Fl.t Lt. Rajan Dhall Hospital New Delhi Delhi
India Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER) Pondicherry Tamil Nadu
India KEM Hospital Pune Pune Maharashtra
India Ruby Hall Clinic,Grant Medical Foundation Pune Maharashtra
India Sree Chitra Tirunal Institute for Medical Sciences and Technology Trivandrum Kerala
Israel Rambam Medical Center Haifa
Israel Assuta Medical Centers Tel-Aviv
Italy Cardiology and CCU - Ospedali Riuniti Ancona Ancona Marche
Italy Ospedale Regionale Umberto Parini Aosta
Italy Azienda Ospedaliera S. Croce e Carle Cuneo Piemonte
Italy Ospedale "G.B. Morgagni - L. Pierantoni" Forli (AUSL della Romagna) Forli Emilia-Romagna
Italy Policlinico di Monza, Monza MB Monza MB
Italy Clinica Mediterranea Naples
Italy AORN Dei Colli "V. Monaldi" UOC Cardiologia Università della Campania "L.Vanvitelli" Napoli Campania
Italy University of Padua- Cardiology Clinic Padua Veneto
Italy UO Cardiologia Ospedale SS Cosma e Damiano Pescia Tuscany
Italy Humanitas Research Hospital, Rozzano (MI) Rozzano Milano
Italy IRCCS "Casa Sollievo della Sofferenza" San Giovanni Rotondo FG
Italy Azienda Servizi Sanitaria n.3 Alto Friuli-Collinare-Medio Friuli Tolmezzo Udine
Italy Ospedale di Circolo e Fondazione Macchi Varese
Japan Saitama Medical University Hidaka Saitama
Japan Keio University Hospital Shinjuku-Ku Tokyo
Japan National Cerebral and Cardiovascular Center Suita-shi Osaka
Lithuania Vilnius University Hospital Santariskes Clinic Vilnius
Malaysia Institut Jantung Negara Kuala Lumpur Wilayah Persekutuan
Mexico Instituto Mexicano del Seguro Social Benito Juarez DF
Mexico Instituto Nacional de Cardiología "Ignacio Chávez" Mexico City Distrito Federal
Netherlands Cardio Research Hartcentrum OLVG Amsterdam NH
Netherlands Radboudumc Nijmegen
Netherlands Isala Klinieken Zwolle
New Zealand Auckland City Hospital Auckland
New Zealand Waikato Hospital Hamilton Waikato
North Macedonia University Clinic of Cardiology Skopje Republic Of Macedo
Peru Instituto Neuro Cardiovascular De Las Americas Miraflores Lima
Poland University Hospital in Bialystok Bialystok Podlaskie
Poland Department of Coronary Disease, John Paul II Hospital, Jagiellonian University Medical College Krakow Maopolskie
Poland Cardiology Clinic, Medical University in Lodz Lodz Lodzkie
Poland Szpital Kliniczny Przemienienia Panskiego Poznan
Poland Coronary and Structural Heart Diseases Department, Institute of Cardiology Warsaw Mazowieckie
Poland Department of Interventional Cardiology & Angiology, Institute of Cardiology Warsaw Mazowieckie
Poland Institute of Cardiology, Warsaw Warsaw Mazovian
Poland Medical University of Warsaw Warsaw Mazowieckie
Poland Department of Internal Medicine and Cardiology, Infant Jesus Teaching Hospital, Medical University of Warsaw Warszawa Mazowieckie
Poland Military Hospital / Medical University Wroclaw
Poland T.Marciniak Hospital Wroclaw Dolny Slask
Poland Medical University of Silesia, School of Medicine with the Division of Dentistry, Department of Cardiology, Congenital Heart Diseases and Electrotherapy, Silesian Center for Heart Diseases Zabrze Wojewodztwo Slaskie
Portugal Hospital de Santa Marta Lisboa
Portugal Santa Maria University Hospital, Cardiology Department, CHLN Lisbon
Portugal Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE Vila Nova de Gaia
Romania Emergency County Hospital Baia Mare Baia Mare
Romania Emergency Institute of Cardiovascular Diseases ''Prof. Dr. C. C. Iliescu'' Bucharest
Russian Federation National Medical Research Center for Cardiovascuar Surgery Moscow Gorod Moskva
Russian Federation E.Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation Novosibirsk Novosibirskaya Oblast
Russian Federation North-Western State Medical University Saint Petersburg
Russian Federation Federal Almazov North-West Medical Research Centre Saint-Petersburg
Saudi Arabia King AbdulAziz Cardiac Center Riyadh Central Province
Serbia Clinical Center of Serbia Belgrade
Serbia Faculty of Medicine, University of Belgrade; Cardiology Clinic, Clinical Center of Serbia Belgrade
Serbia University Clinical Hospital Zvezdara Belgrade
Serbia University Hospital Center Bezanijska Kosa Belgrade
Serbia Clinical Center Kragujevac Kragujevac
Serbia Clinic for Cardiovascular Diseases, Clinical Center Nis Nis
Serbia Institute of Cardiovascular Diseases Vojvodina, Sremska Kamenica, Serbia and Faculty of Medicine, University of Novi Sad Sremska Kamenica Vojvodina
Singapore National Heart Centre Singapore Singapore
Singapore National University Heart Center Singapore Singapore
Singapore Tan Tock Seng Hospital Singapore
South Africa Groote Schuur Hospital / University of Cape Town Cape Town Western Cape
Spain Complexo Hospitalario Universitario A Coruña (CHUAC) Sergas, Department of Cardiology. INIBIC A Coruña. CIBER-CV. Universidad de A Coruña, Spain A Coruna
Spain Hospital De Bellvitge Barcelona
Spain Hospital de la Santa Creu i Sant Pau Barcelona
Spain Hospital General Universitario Gregorio Maranon Madrid
Spain Hospital La Paz. IdiPaz Madrid
Spain HUVA, Hospital Clínico Universitario Virgen De La Arrixaca Murcia
Spain Hospital Clinico Universitario de Santiago Santiago de Compostela La Coruna
Spain Hospital Universitario y Politecnico La Fe Valencia
Spain Hospital Universitario Miguel Servet Zaragoza
Sweden Karolinska Institutet at Danderyd Hospital Stockholm
Sweden Uppsala University Uppsala
Switzerland Cardiocentro Lugano Ticino
Taiwan Mackay Memorial Hospital Taipei City
Thailand Ramathibodi Hospital Bangkok
Thailand Maharaj Nakorn Chiang Mai Hospital Chiang Mai Meung
United Kingdom Hampshire Hospitals NHS Foundation Trust Basingstoke Hampshire
United Kingdom Bedford Hospital NHS Trust Bedford Bedfordshire
United Kingdom Belfast Trust Belfast Antrim
United Kingdom South Eastern Health and Social Care Belfast Northern Ireland
United Kingdom Blackpool Teaching Hospitals Blackpool Lancashire
United Kingdom Royal Bournemouth Hospital Bournemouth Dorset
United Kingdom Bradford Royal Infirmary Bradford West Yorkshire
United Kingdom Papworth Hospital Cambridge Cambridgeshire
United Kingdom Broomfield Hospital Chelmsford Essex
United Kingdom University of Glasgow Clydebank Strathclyde
United Kingdom The University of Hull/Castle Hill Hospital Cottingham East Yorkshire
United Kingdom Cardiovascular Research Unit, Craigavon Area Hospital Craigavon Northern Ireland
United Kingdom Dorset County Hospital Dorchester Dorset
United Kingdom Russells Hall Hospital Dudley West Midlands
United Kingdom Royal Infirmary of Edinburgh Edinburgh Scotland
United Kingdom Northwick Park Hospital Harrow/ Royal Brompton Hospital London Harrow Middlesex
United Kingdom Imperial College Healthcare NHS Trust London
United Kingdom King's College NHS Foundation Hospital London
United Kingdom Royal Free London NHS Foundation Trust London
United Kingdom University College London Hospitals NHS Foundation Trust/Barts Health NHS Trust London
United Kingdom Luton and Dunstable University Hospital NHS FT Luton Berdfordshire
United Kingdom Central Manchester University Hospital Manchester
United Kingdom The James Cook University Hospital, Middlesbrough Middlesbrough Cleveland
United Kingdom Nottingham University Hospitals Nottingham Notts
United Kingdom The Pennine Acute Hospitals NHS Trust Oldham Lancashire
United Kingdom Peterborough City Hospital Peterborough Cambs
United Kingdom Pinderfields Hospital Wakefield West Yorkshire
United Kingdom Southend University Hospital Westcliff-on-Sea Essex
United States Albany Medical Center Hospital Albany New York
United States Capital Cardiology Associates Albany New York
United States Samuel Stratton VA Medical Center of Albany NY Albany New York
United States Asheville Cardiology Associates Asheville North Carolina
United States Emory University Atlanta Georgia
United States University of Maryland Medical Center Baltimore Maryland
United States University of Washington Medical Center Bellevue Washington
United States NIH Heart Center at Suburban Hospital Bethesda Maryland
United States Walter Reed National Military Medical Center Bethesda Maryland
United States Saint Luke's Hospital and Health Network Bethlehem Pennsylvania
United States Cedars Sinai Medical Center Beverly Hills California
United States UAB Vascular Biology and Hypertension Program Birmingham Alabama
United States Boston Medical Center Boston Massachusetts
United States Brigham & Women's Hospital, Harvard Medical School Boston Massachusetts
United States Jacobi Medical Center Bronx New York
United States NYU-HHC Lincoln Medical and Mental Health Center Bronx New York
United States Coney Island Hospital Brooklyn New York
United States New York -Presbyterian/Brooklyn Methodist Hospital Brooklyn New York
United States NYU-HHC Kings County Hospital Center Brooklyn New York
United States NYU-HHC Woodhull Hospital Brooklyn New York
United States Holy Spirit Hospital Cardiovascular Institute Camp Hill Pennsylvania
United States Cardiovascular Associates, Ltd. Chesapeake Virginia
United States Cincinnati VA Medical Center Cincinnati Ohio
United States Louis Stokes Cleveland Veterans Affairs Medical Center Cleveland Ohio
United States Ohio Health Grant Medical Center Columbus Ohio
United States NYP Medical Medical Group Hudson Valley Cardiology Cortlandt Manor New York
United States V.A. North Texas Health Care System Dallas Texas
United States Midwest Cardiovascular Research Foundation Davenport Iowa
United States Daytona Heart Group Daytona Beach Florida
United States Atlanta VA Medical Center Decatur Georgia
United States Henry Ford Health System Detroit Michigan
United States Doylestown Health Cardiology Doylestown Pennsylvania
United States Duke University Medical Center Durham North Carolina
United States Englewood Hospital and Medical Center Englewood New Jersey
United States Advanced Heart Care Group Fairview Heights Illinois
United States Sanford Health Fargo North Dakota
United States New York University - Langone Cardiovascular Associates Flushing New York
United States UCSF - Fresno Community Regional Medical Center Fresno California
United States Malcom Randall VAMC Gainesville Florida
United States Spectrum Health Grand Rapids Michigan
United States Baylor College of Medicine Houston Texas
United States Baylor St. Luke's Medical Center Houston Texas
United States Houston Heart & Vascular Associates Houston Texas
United States Indiana University/Krannert Institute of Cardiology Indianapolis Indiana
United States University of Iowa Hospitals and Clinics Iowa City Iowa
United States Mayo Clinic Florida Jacksonville Florida
United States Conemaugh Valley Memorial Hospital Johnstown Pennsylvania
United States Kansas City VA Medical Center Kansas City Missouri
United States Saint Luke's Hospital Kansas City Missouri
United States Mid Valley Cardiology Kingston New York
United States Gundersen Lutheran Medical Center La Crosse Wisconsin
United States Cardiovascular Specialists of Southwest Louisiana Lake Charles Louisiana
United States Lexington VA Medical Center Lexington Kentucky
United States University of Kentucky Lexington Kentucky
United States South Denver Cardiology Associates, P.C. Littleton Colorado
United States Ronald Reagan UCLA Medical Center Los Angeles California
United States University of Louisville Louisville Kentucky
United States Medical Center of the Rockies Loveland Colorado
United States Stroobants Cardiovascular Center Lynchburg Virginia
United States Northwell Health - Manhasset Manhasset New York
United States Loyola University Medical Center Maywood Illinois
United States NYU Winthrop Mineola New York
United States Minneapolis VAMC Minneapolis Minnesota
United States University of Minnesota Minneapolis Minnesota
United States Saint Thomas Hospital Nashville Tennessee
United States Vanderbilt University Medical Center Nashville Tennessee
United States Beth Israel Medical Center New York New York
United States Columbia University Medical Center New York New York
United States Icahn School of Medicine at Mount Sinai New York New York
United States Mount Sinai Saint Luke's Hospital New York New York
United States NYU Langone Medical Center-Bellevue Hospital New York New York
United States NYU New York Medical Associates New York New York
United States VA New York Harbor Health Care System New York New York
United States University of California Irvine Medical Center Orange California
United States Palo Alto Medical Foundation Research Institute Palo Alto California
United States VA Palo Alto HealthCare System Palo Alto California
United States Baylor Research Institute at Legacy Heart Center Plano Texas
United States The Heart Hospital Baylor Plano Texas
United States AtlantiCare Regional Medical Center Pomona New Jersey
United States Oregon Health & Science University Portland Oregon
United States Providence Heart and Vascular Institute Portland Oregon
United States Miriam Hospital Providence Rhode Island
United States Mayo Clinic Rochester Minnesota
United States University of Rochester Rochester New York
United States Hackensack University Medical Center Saddle Brook New Jersey
United States Covenant Medical Center, Inc. Saginaw Michigan
United States HealthEast Saint Joseph's Hospital Saint Paul Minnesota
United States Salt Lake City VA Medical Center Salt Lake City Utah
United States Audie Murphy V.A. San Antonio Texas
United States Kaiser Permanente San Jose San Jose California
United States Coastal Heart Medical Group Santa Ana California
United States Cardiovascular Center of Sarasota Sarasota Florida
United States Sarasota Memorial Hospital Sarasota Florida
United States Cardiology Associates of Schenectady P.C. Schenectady New York
United States Providence - Providence Park Hospital Southfield Michigan
United States Stanford University School of Medicine Stanford California
United States Medicus Alliance Clinical Research Org., Inc. Sugar Land Texas
United States University of South Florida Tampa Florida
United States Torrance Memorial Medical Center Torrance California
United States Oklahoma Heart Institute Tulsa Oklahoma
United States Kent Hospital Warwick Rhode Island
United States VA Connecticut Healthcare System West Haven Connecticut
United States VA Boston Healthcare System West Roxbury Massachusetts
United States VAMC-White River Junction White River Junction Vermont
United States Wichita Falls Heart Clinic Wichita Falls Texas
United States Winchester Cardiology and Vascular Medicine, PC Winchester Virginia
United States Saint Vincent Hospital at Worcester Medical Center Worcester Massachusetts
United States Michigan Heart, PC Ypsilanti Michigan
United States Yuma Regional Medical Center Yuma Arizona

Sponsors (16)

Lead Sponsor Collaborator
NYU Langone Health Albany Stratton VA Medical Center, Cedars-Sinai Medical Center, Columbia University, Duke University, East Carolina University, Emory University, Harvard University, Massachusetts General Hospital, Montreal Heart Institute, National Heart, Lung, and Blood Institute (NHLBI), New York University, Stanford University, University of British Columbia, University of Missouri, Kansas City, Vanderbilt University

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Egypt,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Japan,  Lithuania,  Malaysia,  Mexico,  Netherlands,  New Zealand,  North Macedonia,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Saudi Arabia,  Serbia,  Singapore,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  United Kingdom, 

References & Publications (4)

Hochman JS, Reynolds HR, Bangalore S, O'Brien SM, Alexander KP, Senior R, Boden WE, Stone GW, Goodman SG, Lopes RD, Lopez-Sendon J, White HD, Maggioni AP, Shaw LJ, Min JK, Picard MH, Berman DS, Chaitman BR, Mark DB, Spertus JA, Cyr DD, Bhargava B, Ruzyllo W, Wander GS, Chernyavskiy AM, Rosenberg YD, Maron DJ; ISCHEMIA Research Group. Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial. JAMA Cardiol. 2019 Mar 1;4(3):273-286. doi: 10.1001/jamacardio.2019.0014. Erratum In: JAMA Cardiol. 2019 May 1;4(5):497. — View Citation

ISCHEMIA Trial Research Group; Maron DJ, Hochman JS, O'Brien SM, Reynolds HR, Boden WE, Stone GW, Bangalore S, Spertus JA, Mark DB, Alexander KP, Shaw L, Berger JS, Ferguson TB Jr, Williams DO, Harrington RA, Rosenberg Y. International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial: Rationale and design. Am Heart J. 2018 Jul;201:124-135. doi: 10.1016/j.ahj.2018.04.011. Epub 2018 Apr 21. — View Citation

Maron DJ, Stone GW, Berman DS, Mancini GB, Scott TA, Byrne DW, Harrell FE Jr, Shaw LJ, Hachamovitch R, Boden WE, Weintraub WS, Spertus JA. Is cardiac catheterization necessary before initial management of patients with stable ischemic heart disease? Results from a Web-based survey of cardiologists. Am Heart J. 2011 Dec;162(6):1034-1043.e13. doi: 10.1016/j.ahj.2011.09.001. — View Citation

Phillips LM, Hachamovitch R, Berman DS, Iskandrian AE, Min JK, Picard MH, Kwong RY, Friedrich MG, Scherrer-Crosbie M, Hayes SW, Sharir T, Gosselin G, Mazzanti M, Senior R, Beanlands R, Smanio P, Goyal A, Al-Mallah M, Reynolds H, Stone GW, Maron DJ, Shaw LJ. Lessons learned from MPI and physiologic testing in randomized trials of stable ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA. J Nucl Cardiol. 2013 Dec;20(6):969-75. doi: 10.1007/s12350-013-9773-4. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Primary Composite Outcome: Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest 3.2 year follow-up (median)
Primary Cumulative Event Rate of Primary Composite Outcome (Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest) This measure represents the estimated cumulative probability of experiencing the primary endpoint within the indicated timeframe in each treatment group. The interpretation of the measure is similar to Kaplan-Meier event rates. Estimates are expressed as percentages ranging from 0% (endpoint is certain not to occur) to 100% (endpoint is certain to occur). 5 years
Primary Number of Participants That Experienced Death From Cardiovascular Causes or Myocardial Infarction 5 years
Primary Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction This measure represents the estimated cumulative probability of experiencing Death from cardiovascular causes or myocardial infarction within the indicated timeframe in each treatment group. The interpretation of the measure is similar to Kaplan-Meier event rates. Estimates are expressed as percentages ranging from 0% (endpoint is certain not to occur) to 100% (endpoint is certain to occur). 5 years
Primary Number of Participants That Experienced Death From Any Cause 5 years
Primary Cumulative Event Rate of Death From Any Cause 5 years
Primary Number of Participants That Experienced Myocardial Infarction 5 years
Primary Cumulative Event Rate of Myocardial Infarction 5 years
Primary Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative The primary composite outcome includes death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. 5 years
Primary Estimated Difference in Cumulative Event Rate of Death From Cardiovascular Causes: Invasive Minus Conservative or Myocardial Infarction Between Invasive and Conservative Strategies 5 years
Primary Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative 5 years
Primary Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative 5 years
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