Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT)

Heart Failure Clinical Trial

— EchoCRT  

Official title:

Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00683696
• Other study ID #: EchoCRT
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: August 30, 2007
• Last updated: January 12, 2018
• Start date: August 2008
• Est. completion date: March 2013

Study information

• Verified date: January 2018
• Source: Biotronik, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1680
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Ventricular Dyssynchrony

Intervention

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.

Locations

Country	Name	City	State
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
Austria	LKH Universitatsklinikum Graz	Graz
Belgium	OLV Hospital (OLV Ziekenhuis) Aalst	Aalst
Belgium	Universitair Ziekenhuis Brussel	Brussels
Canada	Edmonton Cardiology	Edmonton
Canada	UHN Toronto General Hospital	Toronto	Ontario
Czechia	Olomouc University Hospital	Olomouc
Czechia	IKEM - Institute for Clinical and Experimental Medicine	Prague
Czechia	Na Homolce Hospital	Prague
Denmark	Aalborg Sygehus	Aalborg
Denmark	Skejby Sygehus Aarhus	Aarhus
Denmark	Rigshospitalet	Copenhagen
Denmark	Gentofte Hospital	Hellerup
France	Nouvelles Cliniques Nantes	Nantes
France	CHU Pontchaillou de Rennes	Rennes
France	CHU Charles Nicolle	Rouen
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	Klinikum Lüdenscheid	Lüdenscheid
Germany	St. Marien Hospital Lunen	Lunen
Germany	University Hospital of Magdeburg	Magdeburg
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
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
Netherlands	VU MC Amsterdam	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Poland	Instytut Kardiologii	Warsaw
Poland	4 Wojskowy Szpital Kliniczny	Wroclaw
Portugal	Hospital Santa Maria de Lisboa	Lisbon
Portugal	Hospital Santa Marta	Lisbon
Spain	University of Alicante General Hospital	Alicante
Spain	Hospital Clinic of Barcelona	Barcelona
Switzerland	Hopitaux Universitaires de Geneve	Geneve
Switzerland	CHU Vaudois Lausanne	Lausanne
Switzerland	Triemli Hospital (Stadtspital Triemli)	Zurich
Switzerland	University of Zurich Hospital	Zurich
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 States	Lehigh Valley Heart Specialists	Allentown	Pennsylvania
United States	Cardiology Center of Amarillo	Amarillo	Texas
United States	Emory University	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital	Atlanta	Georgia
United States	Texas Cardiac Arrhythmia	Austin	Texas
United States	Bay Regional Medical Center	Bay City	Michigan
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Deborah Heart and Lung Center	Browns Mills	New Jersey
United States	Sanger Heart & Vascular Institute	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Lindner Clinical Trial Center	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	South Carolina Heart Center	Columbia	South Carolina
United States	The Ohio State University Richard M. Ross Heart Hospital	Columbus	Ohio
United States	John Muir Medical Center	Concord	California
United States	Cardiology Associates of Corpus Christi	Corpus Christi	Texas
United States	Duke University	Durham	North Carolina
United States	INOVA Fairfax Hospital	Falls Church	Virginia
United States	Hartford Hospital	Hartford	Connecticut
United States	Community Heart and Vascular	Indianapolis	Indiana
United States	St. Francis Medical Group	Indianapolis	Indiana
United States	Kansas City Heart Foundation	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Osceola Regional Medical Center	Kissimmee	Florida
United States	Thoracic & Cardiovascular Healthcare Foundation	Lansing	Michigan
United States	Central Baptist Hospital	Lexington	Kentucky
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Bon Secours Heart & Vascular Institute	Mechanicsville	Virginia
United States	The Stern Cardiovascular Center	Memphis	Tennessee
United States	University of Miami	Miami	Florida
United States	Aurora Cardiovascular Services	Milwaukee	Wisconsin
United States	St. Lukes-Roosevelt Hospital Center	New York	New York
United States	Drexel Cardiology	Philadelphia	Pennsylvania
United States	Jefferson Heart Institute, Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health Sciences University	Portland	Oregon
United States	Desert Cardiology	Rancho Mirage	California
United States	Bon Secours Heart & Vascular Institute	Richmond	Virginia
United States	Virginia Cardiovascular Specialists	Richmond	Virginia
United States	Virginia Cardiovascular Specialists	Richmond	Virginia
United States	University of Rochester	Rochester	New York
United States	Washington University	Saint Louis	Missouri
United States	United Heart and Vascular Center	Saint Paul	Minnesota
United States	University of California San Francisco	San Francisco	California
United States	Kootenai Heart Clinics	Spokane	Washington
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Tampa General Hospital	Tampa	Florida
United States	Tampa General Medical Center	Tampa	Florida
United States	Promedica Northwest Ohio Cardiology Consultants	Toledo	Ohio
United States	North Mississippi Medical Center	Tupelo	Mississippi
United States	Cardiology Associates Medical Group	Ventura	California
United States	Cardiovascular Associates Ltd	Virginia Beach	Virginia
United States	University of Massachusetts	Worcester	Massachusetts
United States	Michigan Heart, P.C./ St. Joseph Mercy Hospital	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Biotronik, Inc.	University of Zurich

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  Denmark,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Portugal,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite Primary Endpoint: Number of Subjects With First Hospitalization for Worsening Heart Failure or Death	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.	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
Primary	Number of Subjects That Underwent Implant Attempt Without System- or Implant-Related Complications (Complication-Free)	The primary safety endpoint will evaluate the complication-free rate of the Lumax HF-T CRT-D devices in the narrow QRS subject population.	6 months
Secondary	Rate of Hospitalizations for Worsening Heart Failure (Hospitalizations Per Subject-year)	Evaluate the effects of CRT=ON compared to CRT=OFF on the rate of hospitalization for worsening heart failure (WHF).	Study duration from randomization to study exit
Secondary	New York Heart Association (NYHA) Classification Change	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.	6 months
Secondary	Change in Quality of Life (QOL) Scores From Baseline to 6-Month Follow-up	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.	Changes between baseline and 6 months
Secondary	Composite Score of Death, Hospitalization for Worsening Heart Failure and Change in Quality of Life (QOL)	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.	Composite of death, worsening heart failure hospitalization (up to 24 months), and change in QOL (at 6 months)
Secondary	Number of Subjects With All-cause Mortality	Evaluate the all-cause mortality rate between the CRT=ON compared to CRT=OFF group.	From date of randomization up to date of study exit, with a mean treatment duration of 1.6 years