Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT) (EchoCRT)

• ClinicalTrials.gov Identifier: NCT00683696
• Recruitment Status: Terminated
• First Posted: May 23, 2008
• Results First Posted: April 17, 2014
• Last Update Posted: January 17, 2018
• Sponsor: Biotronik, Inc.
• Collaborator: University of Zurich
• Information provided by (Responsible Party): Biotronik, Inc.

Study Description

Brief Summary:

The EchoCRT trial evaluates the effects of Cardiac Resynchronization Therapy (CRT) on mortality and morbidity of subjects with heart failure due to left ventricular systolic dysfunction, already receiving optimized HF medication, with a narrow QRS width (< 130 ms) and echocardiographic evidence of ventricular dyssynchrony.

Condition or disease	Intervention/treatment	Phase
Heart Failure; Ventricular Dyssynchrony	Device: Implantable Cardioverter Defibrillator with Cardiac Resynchronization Therapy (BIOTRONIK Lumax HF-T CRT-D)	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1680 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT)
• Study Start Date: August 2008
• Actual Primary Completion Date: March 2013
• Actual Study Completion Date: March 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: CRT=ON; Cardiac Resynchronization Therapy activated.	Device: Implantable Cardioverter Defibrillator with Cardiac Resynchronization Therapy (BIOTRONIK Lumax HF-T CRT-D); All patients will receive a commercially available BIOTRONIK Lumax HF-T CRT-D system with ICD back-up enabled. Patients will be randomized to CRT=ON or CRT=OFF.; Other Name: Lumax HF-T CRT-D system
Active Comparator: CRT=OFF; Cardiac Resynchronization Therapy deactivated.	Device: Implantable Cardioverter Defibrillator with Cardiac Resynchronization Therapy (BIOTRONIK Lumax HF-T CRT-D); All patients will receive a commercially available BIOTRONIK Lumax HF-T CRT-D system with ICD back-up enabled. Patients will be randomized to CRT=ON or CRT=OFF.; Other Name: Lumax HF-T CRT-D system

Outcome Measures

Primary Outcome Measures :

1. Composite Primary Endpoint: Number of Subjects With First Hospitalization for Worsening Heart Failure or Death [ Time Frame: From date of randomization until date of death from any cause or date of first hospitalization for worsening heart failure, whichever came first, assessed up to date of study exit, with a mean treatment duration of 1.6 years ]
   The primary efficacy endpoint will evaluate the effect of CRT=ON versus CRT=OFF in time to event of a combined endpoint of all-cause mortality or first hospitalization for worsening heart failure.
2. Number of Subjects That Underwent Implant Attempt Without System- or Implant-Related Complications (Complication-Free) [ Time Frame: 6 months ]
   The primary safety endpoint will evaluate the complication-free rate of the Lumax HF-T CRT-D devices in the narrow QRS subject population.

Secondary Outcome Measures :

1. Rate of Hospitalizations for Worsening Heart Failure (Hospitalizations Per Subject-year) [ Time Frame: Study duration from randomization to study exit ]
   Evaluate the effects of CRT=ON compared to CRT=OFF on the rate of hospitalization for worsening heart failure (WHF).
2. New York Heart Association (NYHA) Classification Change [ Time Frame: 6 months ]

   Evaluate the effects of CRT=ON compared to CRT=OFF in relation to the change in NYHA classification.

   NYHA classes:

   Class I - Subjects with cardiac disease, but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation,dyspnea, or anginal pain.

   Class II - Subjects with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.

   Class III - Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain.

   Class IV - Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

3. Change in Quality of Life (QOL) Scores From Baseline to 6-Month Follow-up [ Time Frame: Changes between baseline and 6 months ]
   Quality of Life was evaluated using the Minnesota Living with Heart Failure (MLHF) Quality of Life (QOL) Questionnaire.The questionnaire consists of 21 questions to measure the subjects' perception of how their HF and its treatment affected their ability to live as they wanted during the last month. The questions describe different ways in which some people are affected (i.e. physical, socioeconomic, and psychological impairments). If a question does not apply to a subject or is not related to their HF, then they can answer with a 0. If it does apply to them, then they can rate (from 1 to 5) how much it has affected them. From the 21 questions, the lowest possible total score is 0, and the highest possible total score is 105. A lower score is desirable. Therefore, a negative change in QOL score from baseline to 6 months represents an improvement in quality of life, while a positive change in QOL score from baseline to 6 months represents a worsening in quality of life.
4. Composite Score of Death, Hospitalization for Worsening Heart Failure and Change in Quality of Life (QOL) [ Time Frame: Composite of death, worsening heart failure hospitalization (up to 24 months), and change in QOL (at 6 months) ]

   Evaluate the effects of CRT=ON compared to CRT=OFF in relation to a composite endpoint of all-cause mortality, hospitalization for worsening heart failure and change in the MLHF Quality of Life Questionnaire.

   This composite endpoint used a weighted scoring scale based on the African-American Heart Failure Trial (A-HeFT) study Endpoint Score. (Taylor, AL, Ziesche, S, Yancy, C, et al. Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure. N Engl J Med 2004; 351:2049-57.)

   Composite Endpoint Scoring:

   Vital Status:

   Death (-3),

   Survival to end of trial (0),

   Hospitalization:

   1st hospitalization for HF (-1),

   No hospitalization (0),

   QOL score:*

   Improvement by ≥ 10 units (+2),

   Improvement by 5-9 units (+1),

   Change by < 5 units (0),

   Worsening by 5-9 units (-1),

   Worsening by ≥ 10 (-2).

   Possible total score -6 to +2.

   *QOL score details are provided in Secondary Outcome Measure 5.

5. Number of Subjects With All-cause Mortality [ Time Frame: From date of randomization up to date of study exit, with a mean treatment duration of 1.6 years ]
   Evaluate the all-cause mortality rate between the CRT=ON compared to CRT=OFF group.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men and women 18 years of age or older.
• Understand the nature of the procedure.
• Give written informed consent.
• Willing and able to complete all testing required by the clinical protocol.
• Indication for an implantable cardioverter defibrillator (ICD).
• NYHA class III-IV within the last three months prior to enrollment and at baseline (at baseline only: also Stage C according to ACC/AHA guidelines).
• Stable optimal pharmacologic therapy for HF.
• An ejection fraction ≤ 35% within one year prior to enrollment and confirmed on the baseline echocardiogram.
• Increased left ventricular dimension, defined as LVEDD ≥ 55 mm.
• Resting QRS duration < 130 ms evidenced by a historical 12-lead ECG prior to enrollment and at baseline.

• Ventricular dyssynchrony assessed by echocardiography locally and confirmed by the echo core lab. One of the two following criteria has to be present to include the subject in the study:

  • Intra-left ventricular dyssynchrony measured by color Tissue Doppler Imaging (TDI) with an opposing wall delay of ≥ 80 ms in the 4-chamber or apical long-axis view.
  • Speckle-tracking radial strain septal-posterior wall delay ≥ 130 ms.

Exclusion Criteria:

• Implanted pacemaker or defibrillator with >10% ventricular pacing, as demonstrated by device statistics averaged over at least the last three months prior to enrollment.
• Women who are pregnant, lactating, or planning to become pregnant during the course of the trial.
• Bradycardia pacing indication.
• Surgically correctable primary valvular heart disease, i.e. aortic stenosis, torn cordae, or flail segment.
• Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within the past 3 months prior to enrollment.
• Enzyme-positive myocardial infarction within the past 3 months prior to enrollment.
• Angiographic evidence of coronary disease, candidates for coronary revascularization likely to undergo coronary artery bypass graft surgery or percutaneous coronary intervention in the next 3 months.
• Irreversible brain damage from preexisting cerebral disease.
• Reversible non-ischemic cardiomyopathy such as acute viral myocarditis.
• Permanent second or third degree heart block.
• Chagas disease.
• Persistent or paroxysmal atrial fibrillation within one month prior to enrollment.
• Expected to receive heart transplantation within six months.
• Current inotropic therapy.
• Acutely decompensated heart failure.
• Contrast dye allergy and unable or unwilling to undergo pretreatment with steroids and/or diphenhydramine.
• Life expectancy of less than six months.
• Presence of any disease, other than the subject's cardiac disease associated with a reduced likelihood of survival for the duration of the trial, (e.g. cancer).
• Significant renal insufficiency defined as a serum creatinine > 2.5 mg/dL (> 221 µmol/L) within the last four weeks prior to enrollment..
• Liver failure, defined as three times the upper limit of normal for aminotransferases.
• Participation in any other clinical trial.
• Unable to return for follow-up visits due to distance from the clinic.
• Do not anticipate being a resident of the area for the scheduled duration of the trial.

Contacts and Locations

Locations

United States, California

John Muir Medical Center

Concord, California, United States, 94520

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

Desert Cardiology

Rancho Mirage, California, United States, 92270

University of California San Francisco

San Francisco, California, United States, 94143

Cardiology Associates Medical Group

Ventura, California, United States, 93003

United States, Connecticut

Hartford Hospital

Hartford, Connecticut, United States, 06102

United States, Florida

Osceola Regional Medical Center

Kissimmee, Florida, United States, 34741

University of Miami

Miami, Florida, United States, 33136

Tampa General Hospital

Tampa, Florida, United States, 33606

Tampa General Medical Center

Tampa, Florida, United States

United States, Georgia

Piedmont Hospital

Atlanta, Georgia, United States, 30309

Emory University

Atlanta, Georgia, United States, 30322

Saint Joseph's Hospital

Atlanta, Georgia, United States

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Indiana

St. Francis Medical Group

Indianapolis, Indiana, United States, 46237

Community Heart and Vascular

Indianapolis, Indiana, United States, 46250

United States, Kentucky

Central Baptist Hospital

Lexington, Kentucky, United States, 40503

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114-2696

Boston Medical Center

Boston, Massachusetts, United States, 02118

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Boston Medical Center

Boston, Massachusetts, United States

University of Massachusetts

Worcester, Massachusetts, United States, 01655

United States, Michigan

Bay Regional Medical Center

Bay City, Michigan, United States, 48708

Thoracic & Cardiovascular Healthcare Foundation

Lansing, Michigan, United States, 48910

Michigan Heart, P.C./ St. Joseph Mercy Hospital

Ypsilanti, Michigan, United States, 48197

United States, Minnesota

United Heart and Vascular Center

Saint Paul, Minnesota, United States, 55102

United States, Mississippi

North Mississippi Medical Center

Tupelo, Mississippi, United States

United States, Missouri

Kansas City Heart Foundation

Kansas City, Missouri, United States, 64132

Research Medical Center

Kansas City, Missouri, United States, 64132

Research Medical Center

Kansas City, Missouri, United States

Washington University

Saint Louis, Missouri, United States, 63102

United States, New Jersey

Deborah Heart and Lung Center

Browns Mills, New Jersey, United States, 08015

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

St. Lukes-Roosevelt Hospital Center

New York, New York, United States, 10025

University of Rochester

Rochester, New York, United States, 14642

Stony Brook University Medical Center

Stony Brook, New York, United States, 11794

United States, North Carolina

Sanger Heart & Vascular Institute

Charlotte, North Carolina, United States, 28203

Duke University

Durham, North Carolina, United States

United States, Ohio

Lindner Clinical Trial Center

Cincinnati, Ohio, United States, 45219

University of Cincinnati

Cincinnati, Ohio, United States, 45219

Cleveland Clinic

Cleveland, Ohio, United States, 44145

The Ohio State University Richard M. Ross Heart Hospital

Columbus, Ohio, United States, 43210

Promedica Northwest Ohio Cardiology Consultants

Toledo, Ohio, United States, 43615

United States, Oregon

Oregon Health Sciences University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Lehigh Valley Heart Specialists

Allentown, Pennsylvania, United States, 18103

Drexel Cardiology

Philadelphia, Pennsylvania, United States, 19107

Jefferson Heart Institute, Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States, 19107

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15213

United States, South Carolina

South Carolina Heart Center

Columbia, South Carolina, United States, 29204

United States, Tennessee

The Stern Cardiovascular Center

Memphis, Tennessee, United States, 38138

United States, Texas

Cardiology Center of Amarillo

Amarillo, Texas, United States, 79106

Texas Cardiac Arrhythmia

Austin, Texas, United States, 78705

Cardiology Associates of Corpus Christi

Corpus Christi, Texas, United States, 78404

United States, Virginia

University of Virginia

Charlottesville, Virginia, United States, 22908

INOVA Fairfax Hospital

Falls Church, Virginia, United States, 22042

Bon Secours Heart & Vascular Institute

Mechanicsville, Virginia, United States, 23116

Virginia Cardiovascular Specialists

Richmond, Virginia, United States, 23225

Bon Secours Heart & Vascular Institute

Richmond, Virginia, United States

Virginia Cardiovascular Specialists

Richmond, Virginia, United States

Cardiovascular Associates Ltd

Virginia Beach, Virginia, United States, 23454

United States, Washington

Kootenai Heart Clinics

Spokane, Washington, United States, 99204

United States, Wisconsin

Aurora Cardiovascular Services

Milwaukee, Wisconsin, United States, 53215

Australia

Flinders Medical Center Adelaide

Adelaide, Australia

Princess Alexandra Hospital

Brisbane, Australia

St. Vincent's Hospital

Melbourne, Australia

Sir Charles Gairdner Hospital

Nedland, Australia

Royal Perth Hospital

Perth, Australia

Austria

LKH Universitatsklinikum Graz

Graz, Austria

Belgium

OLV Hospital (OLV Ziekenhuis) Aalst

Aalst, Belgium

Universitair Ziekenhuis Brussel

Brussels, Belgium

Canada, Ontario

UHN Toronto General Hospital

Toronto, Ontario, Canada

Canada

Edmonton Cardiology

Edmonton, Canada

Czechia

Olomouc University Hospital

Olomouc, Czechia

IKEM - Institute for Clinical and Experimental Medicine

Prague, Czechia

Na Homolce Hospital

Prague, Czechia

Denmark

Aalborg Sygehus

Aalborg, Denmark

Skejby Sygehus Aarhus

Aarhus, Denmark

Rigshospitalet

Copenhagen, Denmark

Gentofte Hospital

Hellerup, Denmark

France

Nouvelles Cliniques Nantes

Nantes, France

CHU Pontchaillou de Rennes

Rennes, France

CHU Charles Nicolle

Rouen, France

Germany

Herz- und Diabeteszentrum NRW

Bad Oeynhausen, Germany

Charite Campus Virchow Klinikum

Berlin, Germany

Judisches Krankenhaus Berlin

Berlin, Germany

Evangelisch-Freikirchliches Krankenhaus und Herzzentrum Brandenburg in Bernau

Bernau, Germany

Alfried Krupp Krankenhaus

Essen, Germany

Elisabeth-Krankenhaus Essen

Essen, Germany

Westdeutsches Herzzentrum Essen

Essen, Germany

Asklepios Klinik St. Georg Hamburg

Hamburg, Germany

Universitares Herzzentrum Hamburg GmbH

Hamburg, Germany

Universitatsklinikum Jena

Jena, Germany

Herzzentrum Leipzig GmbH

Leipzig, Germany

St. Marien Hospital Lunen

Lunen, Germany

Klinikum Lüdenscheid

Lüdenscheid, Germany

University Hospital of Magdeburg

Magdeburg, Germany

Israel

Barzilai Medical Center

Ashkelon, Israel

Soroka Medical Center

Beer Sheva, Israel

Hadassah Medical Organization

Jerusalem, Israel

Sourasky Medical Center

Tel Aviv, Israel

Sheba Medical Center

Tel Hashomer, Israel

Italy

A.O.U. Consorziale Policlinico di Bari

Bari, Italy

A.O. Spedali Civili di Brescia

Brescia, Italy

P.O. Santa Maria di Loreto Nuovo

Naples, Italy

A.O.U. Maggiore della Carita

Novara, Italy

Netherlands

VU MC Amsterdam

Amsterdam, Netherlands

Leiden University Medical Center

Leiden, Netherlands

Poland

Instytut Kardiologii

Warsaw, Poland

4 Wojskowy Szpital Kliniczny

Wroclaw, Poland

Portugal

Hospital Santa Maria de Lisboa

Lisbon, Portugal

Hospital Santa Marta

Lisbon, Portugal

Spain

University of Alicante General Hospital

Alicante, Spain

Hospital Clinic of Barcelona

Barcelona, Spain

Switzerland

Hopitaux Universitaires de Geneve

Geneve, Switzerland

CHU Vaudois Lausanne

Lausanne, Switzerland

Triemli Hospital (Stadtspital Triemli)

Zurich, Switzerland

University of Zurich Hospital

Zurich, Switzerland

United Kingdom

University Hospitals of Coventry and Warwickshire

Coventry, United Kingdom

Glenfield Hospital

Leicester, United Kingdom

St. George's Hospital

London, United Kingdom

St. Thomas' Hospital

London, United Kingdom

Russells Hall Hospital

West Midlands, United Kingdom

Sponsors and Collaborators

Biotronik, Inc.

University of Zurich

Investigators

• Study Chair: Frank Ruschitzka, MD; University of Zurich, Switzerland
• Study Chair: Johannes Holzmeister, MD; University of Zurich, Switzerland
• Principal Investigator: William Abraham, MD; Principal Investigator (USA) at The Ohio State University, OH, USA
• Principal Investigator: Jagmeet Singh, MD; Principal Investigator (USA) at Massachusetts General Hospital, MA, USA

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Varma N, Sogaard P, Bax JJ, Abraham WT, Borer JS, Dickstein K, Singh JP, Gras D, Holzmeister J, Brugada J, Ruschitzka F. Interaction of Left Ventricular Size and Sex on Outcome of Cardiac Resynchronization Therapy Among Patients With a Narrow QRS Duration in the EchoCRT Trial. J Am Heart Assoc. 2018 May 27;7(11). pii: e009592. doi: 10.1161/JAHA.118.009592. Erratum in: J Am Heart Assoc. 2018 Jun 17;7(12):.

Tayal B, Gorcsan J 3rd, Bax JJ, Risum N, Olsen NT, Singh JP, Abraham WT, Borer JS, Dickstein K, Gras D, Krum H, Brugada J, Robertson M, Ford I, Holzmeister J, Ruschitzka F, Sogaard P. Cardiac Resynchronization Therapy in Patients With Heart Failure and Narrow QRS Complexes. J Am Coll Cardiol. 2018 Mar 27;71(12):1325-1333. doi: 10.1016/j.jacc.2018.01.042.

Steffel J, Varma N, Robertson M, Singh JP, Bax JJ, Borer JS, Dickstein K, Ford I, Gorcsan J 3rd, Gras D, Krum H, Sogaard P, Holzmeister J, Brugada J, Abraham WT, Ruschitzka F. Effect of Gender on Outcomes After Cardiac Resynchronization Therapy in Patients With a Narrow QRS Complex: A Subgroup Analysis of the EchoCRT Trial. Circ Arrhythm Electrophysiol. 2016 Jun;9(6). pii: e003924. doi: 10.1161/CIRCEP.115.003924.

Ruschitzka F, Abraham WT, Singh JP, Bax JJ, Borer JS, Brugada J, Dickstein K, Ford I, Gorcsan J 3rd, Gras D, Krum H, Sogaard P, Holzmeister J; EchoCRT Study Group. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. N Engl J Med. 2013 Oct 10;369(15):1395-405. doi: 10.1056/NEJMoa1306687. Epub 2013 Sep 2.

• Responsible Party: Biotronik, Inc.
• ClinicalTrials.gov Identifier: NCT00683696
• Other Study ID Numbers: EchoCRT
• First Posted: May 23, 2008
• Results First Posted: April 17, 2014
• Last Update Posted: January 17, 2018
• Last Verified: January 2018

Keywords provided by Biotronik, Inc.:

Cardiac Resynchronization Therapy; Heart Failure; Ventricular Dyssynchrony; Mechanical Dyssynchrony; Intraventricular Dyssynchrony; Echocardiography; Normal QRS; Heart Disease; EchoCRT

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases