Clinical trial NCT00683696: Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT)
Official title: Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Heart Failure
Ventricular Dyssynchrony
Keywords: Cardiac Resynchronization Therapy
Heart Failure
Ventricular Dyssynchrony
Mechanical Dyssynchrony
Intraventricular Dyssynchrony
Echocardiography
Normal QRS
Heart Disease
EchoCRT
Lead sponsor: Biotronik, Inc.
Sponsor class: INDUSTRY
Collaborators: name: University of Zurich
First posted: 2008-05-23
Enrollment: 1680
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Composite Primary Endpoint: Number of Subjects With First Hospitalization for Worsening Heart Failure or Death
timeFrame: 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
measure: Number of Subjects That Underwent Implant Attempt Without System- or Implant-Related Complications (Complication-Free)
timeFrame: 6 months
Secondary outcomes:
measure: Rate of Hospitalizations for Worsening Heart Failure (Hospitalizations Per Subject-year)
timeFrame: Study duration from randomization to study exit
measure: New York Heart Association (NYHA) Classification Change
timeFrame: 6 months
measure: Change in Quality of Life (QOL) Scores From Baseline to 6-Month Follow-up
timeFrame: Changes between baseline and 6 months
measure: Composite Score of Death, Hospitalization for Worsening Heart Failure and Change in Quality of Life (QOL)
timeFrame: Composite of death, worsening heart failure hospitalization (up to 24 months), and change in QOL (at 6 months)
measure: Number of Subjects With All-cause Mortality
timeFrame: From date of randomization up to date of study exit, with a mean treatment duration of 1.6 years
Other outcomes:
Locations:
city: Concord
country: United States
facility: John Muir Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Rancho Mirage
country: United States
facility: Desert Cardiology
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Ventura
country: United States
facility: Cardiology Associates Medical Group
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Kissimmee
country: United States
facility: Osceola Regional Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Medical Center
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Saint Joseph's Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: St. Francis Medical Group
state: Indiana
city: Indianapolis
country: United States
facility: Community Heart and Vascular
state: Indiana
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Bay City
country: United States
facility: Bay Regional Medical Center
state: Michigan
city: Lansing
country: United States
facility: Thoracic & Cardiovascular Healthcare Foundation
state: Michigan
city: Ypsilanti
country: United States
facility: Michigan Heart, P.C./ St. Joseph Mercy Hospital
state: Michigan
city: Saint Paul
country: United States
facility: United Heart and Vascular Center
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City Heart Foundation
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Browns Mills
country: United States
facility: Deborah Heart and Lung Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: St. Lukes-Roosevelt Hospital Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Charlotte
country: United States
facility: Sanger Heart & Vascular Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Lindner Clinical Trial Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Richard M. Ross Heart Hospital
state: Ohio
city: Toledo
country: United States
facility: Promedica Northwest Ohio Cardiology Consultants
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Heart Specialists
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel Cardiology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Heart Institute, Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Columbia
country: United States
facility: South Carolina Heart Center
state: South Carolina
city: Memphis
country: United States
facility: The Stern Cardiovascular Center
state: Tennessee
city: Amarillo
country: United States
facility: Cardiology Center of Amarillo
state: Texas
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia
state: Texas
city: Corpus Christi
country: United States
facility: Cardiology Associates of Corpus Christi
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: INOVA Fairfax Hospital
state: Virginia
city: Mechanicsville
country: United States
facility: Bon Secours Heart & Vascular Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Cardiovascular Specialists
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Heart & Vascular Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Cardiovascular Specialists
state: Virginia
city: Virginia Beach
country: United States
facility: Cardiovascular Associates Ltd
state: Virginia
city: Spokane
country: United States
facility: Kootenai Heart Clinics
state: Washington
city: Milwaukee
country: United States
facility: Aurora Cardiovascular Services
state: Wisconsin
city: Adelaide
country: Australia
facility: Flinders Medical Center Adelaide
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
city: Melbourne
country: Australia
facility: St. Vincent's Hospital
city: Nedland
country: Australia
facility: Sir Charles Gairdner Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Graz
country: Austria
facility: LKH Universitatsklinikum Graz
city: Aalst
country: Belgium
facility: OLV Hospital (OLV Ziekenhuis) Aalst
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Toronto
country: Canada
facility: UHN Toronto General Hospital
state: Ontario
city: Edmonton
country: Canada
facility: Edmonton Cardiology
city: Olomouc
country: Czechia
facility: Olomouc University Hospital
city: Prague
country: Czechia
facility: IKEM - Institute for Clinical and Experimental Medicine
city: Prague
country: Czechia
facility: Na Homolce Hospital
city: Aalborg
country: Denmark
facility: Aalborg Sygehus
city: Aarhus
country: Denmark
facility: Skejby Sygehus Aarhus
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Nantes
country: France
facility: Nouvelles Cliniques Nantes
city: Rennes
country: France
facility: CHU Pontchaillou de Rennes
city: Rouen
country: France
facility: CHU Charles Nicolle
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW
city: Berlin
country: Germany
facility: Charite Campus Virchow Klinikum
city: Berlin
country: Germany
facility: Judisches Krankenhaus Berlin
city: Bernau
country: Germany
facility: Evangelisch-Freikirchliches Krankenhaus und Herzzentrum Brandenburg in Bernau
city: Essen
country: Germany
facility: Alfried Krupp Krankenhaus
city: Essen
country: Germany
facility: Elisabeth-Krankenhaus Essen
city: Essen
country: Germany
facility: Westdeutsches Herzzentrum Essen
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg Hamburg
city: Hamburg
country: Germany
facility: Universitares Herzzentrum Hamburg GmbH
city: Jena
country: Germany
facility: Universitatsklinikum Jena
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH
city: Lunen
country: Germany
facility: St. Marien Hospital Lunen
city: Lüdenscheid
country: Germany
facility: Klinikum Lüdenscheid
city: Magdeburg
country: Germany
facility: University Hospital of Magdeburg
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Bari
country: Italy
facility: A.O.U. Consorziale Policlinico di Bari
city: Brescia
country: Italy
facility: A.O. Spedali Civili di Brescia
city: Naples
country: Italy
facility: P.O. Santa Maria di Loreto Nuovo
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carita
city: Amsterdam
country: Netherlands
facility: VU MC Amsterdam
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Warsaw
country: Poland
facility: Instytut Kardiologii
city: Wroclaw
country: Poland
facility: 4 Wojskowy Szpital Kliniczny
city: Lisbon
country: Portugal
facility: Hospital Santa Maria de Lisboa
city: Lisbon
country: Portugal
facility: Hospital Santa Marta
city: Alicante
country: Spain
facility: University of Alicante General Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Geneve
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Lausanne
country: Switzerland
facility: CHU Vaudois Lausanne
city: Zurich
country: Switzerland
facility: Triemli Hospital (Stadtspital Triemli)
city: Zurich
country: Switzerland
facility: University of Zurich Hospital
city: Coventry
country: United Kingdom
facility: University Hospitals of Coventry and Warwickshire
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
city: London
country: United Kingdom
facility: St. George's Hospital
city: London
country: United Kingdom
facility: St. Thomas' Hospital
city: West Midlands
country: United Kingdom
facility: Russells Hall Hospital
Study officials:
affiliation: University of Zurich, Switzerland
name: Frank Ruschitzka, MD
role: STUDY_CHAIR
affiliation: University of Zurich, Switzerland
name: Johannes Holzmeister, MD
role: STUDY_CHAIR
affiliation: Principal Investigator (USA) at The Ohio State University, OH, USA
name: William Abraham, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Principal Investigator (USA) at Massachusetts General Hospital, MA, USA
name: Jagmeet Singh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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):e009592. doi: 10.1161/JAHA.118.009592.
citation: 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.
citation: 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):e003924. doi: 10.1161/CIRCEP.115.003924.
citation: 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.