Echocardiography Guided Cardiac Resynchronization Therapy... | NCT00683696

NCT00683696

Status Module

Name	Class
University of Zurich	OTHER

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
CRT=ON	Experimental	Cardiac Resynchronization Therapy activated.	Device: Implantable Cardioverter Defibrillator with Cardiac Resynchronization Therapy (BIOTRONIK Lumax HF-T CRT-D)
CRT=OFF	Active Comparator	Cardiac Resynchronization Therapy deactivated.	Device: Implantable Cardioverter Defibrillator with Cardiac Resynchronization Therapy (BIOTRONIK Lumax HF-T CRT-D)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Implantable Cardioverter Defibrillator with Cardiac Resynchronization Therapy (BIOTRONIK Lumax HF-T CRT-D)	Device	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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
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 Outcomes

Measure	Description	Time Frame
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
New York Heart Association (NYHA) Classification Change

Eligibility Module

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.

Name	Affiliation	Role
Frank Ruschitzka, MD	University of Zurich, Switzerland	Study Chair
Johannes Holzmeister, MD	University of Zurich, Switzerland	Study Chair
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	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
John Muir Medical Center		Concord	California	94520	United States
Cedars-Sinai Medical Center

PubMed Identifier	Type	Citation	Retractions
29807890	Derived	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.
29566816

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	CRT=ON	Cardiac Resynchronization Therapy activated. Subject implanted with BIOTRONIK Lumax HF-T CRT-D system with ICD back-up enabled and randomized to CRT=ON.
FG001	CRT=OFF

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

This analysis was carried out according to the intention-to-treat principle. Follow-up was censored at study closure, date of death, LVAD, heart transplant, withdrawal from the study, or loss to follow-up, whichever came first. 4 deaths in CRT OFF group and 1 death in CRT ON group were after LVAD/transplant and are not included in this analysis.

Posted

Number

participants

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

ID	Title	Description
OG000	CRT=ON	Cardiac Resynchronization Therapy activated.
OG001	CRT=OFF	Cardiac Resynchronization Therapy deactivated.

Units	Counts
Participants	OG000404 OG001405

Title

Denominators

Categories

Title	Measurements
	OG000116 OG001102

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.

The primary safety endpoint included all subjects undergoing an implant procedure.

Posted

Number

participants

6 months

ID	Title	Description
OG000	Subjects That Underwent an Implant Attempt

Units	Counts
Participants	OG000855

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).

Posted

Number

Hospitalizations per subj-yr

Study duration from randomization to study exit

ID	Title	Description
OG000	CRT=ON	Cardiac Resynchronization Therapy activated.
OG001	CRT=OFF	Cardiac Resynchronization Therapy deactivated.

Units	Counts
Participants	OG000

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.

Subjects with Baseline & 6-month NYHA classification. 18 subjects (9 CRT ON, 9 CRT OFF) that were in the study at least 6 months and that did not have 6-month NYHA data, had the most recent post-randomization NYHA inputted using the Last Observation Carried Forward (LOCF) principle.

Posted

Count of Participants

Participants

6 months

ID	Title	Description
OG000	CRT=ON	Cardiac Resynchronization Therapy activated.
OG001	CRT=OFF

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.

Subjects with Baseline & 6-month QOL scores. 25 subjects (15 CRT ON, 10 CRT OFF) that were in the study at least 6 months and that did not have 6-month QOL data, had 3-month data inputted using the LOCF principle.

Posted

Mean

Standard Deviation

units on a scale

Changes between baseline and 6 months

ID	Title	Description
OG000	CRT=ON	Cardiac Resynchronization Therapy activated.
OG001	CRT=OFF

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.

Subjects with a potential of 24 months of follow-up.

Posted

Mean

Standard Deviation

Composite score

Composite of death, worsening heart failure hospitalization (up to 24 months), and change in QOL (at 6 months)

ID	Title	Description
OG000	CRT=ON	Cardiac Resynchronization Therapy activated.
OG001	CRT=OFF	Cardiac Resynchronization Therapy deactivated.

Secondary

Number of Subjects With All-cause Mortality

Evaluate the all-cause mortality rate between the CRT=ON compared to CRT=OFF group.

Posted

Count of Participants

Participants

From date of randomization up to date of study exit, with a mean treatment duration of 1.6 years

ID	Title	Description
OG000	CRT=ON	Cardiac Resynchronization Therapy activated.
OG001	CRT=OFF	Cardiac Resynchronization Therapy deactivated.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Statistical Information
Worsening heart failure	Cardiac disorders	EG000213 events101 affected404 at risk EG001181 events93 affected405 at risk
Atrial arrhythmia	Cardiac disorders	EG00034 events27 affected404 at risk EG00135 events25 affected405 at risk
Ventricular arrhythmia	Cardiac disorders	EG00036 events26 affected404 at risk EG00129 events22 affected405 at risk
Chest pain	Cardiac disorders	EG00031 events16 affected404 at risk EG00126 events21 affected405 at risk
Other cardiovascular	Cardiac disorders	EG00021 events18 affected404 at risk EG00120 events17 affected405 at risk
Dyspnea	Cardiac disorders	EG00016 events16 affected404 at risk EG00112 events11 affected405 at risk
Coronary artery disease	Cardiac disorders	EG00013 events13 affected404 at risk EG00111 events10 affected405 at risk
Infection	Infections and infestations	EG00077 events58 affected404 at risk EG00154 events45 affected405 at risk
Gastrointestinal disorder	Gastrointestinal disorders	EG00068 events43 affected404 at risk EG00141 events28 affected405 at risk
Other noncardiovascular	General disorders	EG00054 events40 affected404 at risk EG00155 events36 affected405 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	EG00027 events14 affected404 at risk EG00138 events22 affected405 at risk
Renal disorder	Renal and urinary disorders	EG00038 events28 affected404 at risk EG00119 events16 affected405 at risk
Musculoskeletal disorder	Musculoskeletal and connective tissue disorders	EG00032 events25 affected404 at risk EG00118 events15 affected405 at risk
Nervous system disorder	Nervous system disorders	EG00016 events13 affected404 at risk EG0015 events5 affected405 at risk
ICD lead	Cardiac disorders	EG00026 events23 affected404 at risk EG00113 events13 affected405 at risk
Lead for right atrial pacing	Cardiac disorders	EG00021 events18 affected404 at risk EG0015 events5 affected405 at risk
Lead for left ventricular pacing	Cardiac disorders	EG00021 events18 affected404 at risk EG0014 events4 affected405 at risk
Implantation related	Surgical and medical procedures	EG00019 events17 affected404 at risk EG00118 events16 affected405 at risk
Hypotension	Cardiac disorders	EG00014 events11 affected404 at risk EG0019 events9 affected405 at risk
Angina	Cardiac disorders	EG0008 events7 affected404 at risk EG00113 events12 affected405 at risk
Peripheral vascular disease	Cardiac disorders	EG0008 events6 affected404 at risk EG00112 events10 affected405 at risk
Syncope	Cardiac disorders	EG0008 events8 affected404 at risk EG0019 events7 affected405 at risk
Cardiac arrest	Cardiac disorders	EG00013 events11 affected404 at risk EG0013 events3 affected405 at risk
Myocardial infarction	Cardiac disorders	EG0006 events6 affected404 at risk EG0018 events6 affected405 at risk
Anemia	Cardiac disorders	EG0009 events5 affected404 at risk EG0014 events4 affected405 at risk
Stroke	Cardiac disorders	EG0007 events6 affected404 at risk EG0016 events6 affected405 at risk
Pulmonary embolism	Cardiac disorders	EG0005 events5 affected404 at risk EG0017 events5 affected405 at risk
Transischemic attack	Cardiac disorders	EG0006 events6 affected404 at risk EG0014 events4 affected405 at risk
Thrombosis	Cardiac disorders	EG0003 events3 affected404 at risk EG0016 events5 affected405 at risk
Fluid accumulation	Cardiac disorders	EG0007 events5 affected404 at risk EG0011 events1 affected405 at risk
Pulmonary edema	Cardiac disorders	EG0005 events5 affected404 at risk EG0013 events2 affected405 at risk
Cardiac catheterization	Cardiac disorders	EG0005 events5 affected404 at risk EG0012 events2 affected405 at risk
Cardiovascular medication related	Cardiac disorders	EG0003 events3 affected404 at risk EG0014 events4 affected405 at risk
Dizziness	Cardiac disorders	EG0004 events4 affected404 at risk EG0013 events3 affected405 at risk
Pleural effusion	Cardiac disorders	EG0004 events4 affected404 at risk EG0012 events2 affected405 at risk
Valvular heart disease	Cardiac disorders	EG0005 events4 affected404 at risk EG0011 events1 affected405 at risk
Abdominal Aortic Aneurysm	Cardiac disorders	EG0003 events3 affected404 at risk EG0012 events2 affected405 at risk
Edema	Cardiac disorders	EG0001 events1 affected404 at risk EG0013 events3 affected405 at risk
Increased INR	Cardiac disorders	EG0003 events2 affected404 at risk EG0011 events1 affected405 at risk
Palpitations	Cardiac disorders	EG0001 events1 affected404 at risk EG0012 events2 affected405 at risk
Bradycardia	Cardiac disorders	EG0001 events1 affected404 at risk EG0011 events1 affected405 at risk
Dilated cardiomyopathy	Cardiac disorders	EG0001 events1 affected404 at risk EG0011 events1 affected405 at risk
Hypertension	Cardiac disorders	EG0001 events1 affected404 at risk EG0011 events1 affected405 at risk
Ischemic cardiomyopathy	Cardiac disorders	EG0001 events1 affected404 at risk EG0011 events1 affected405 at risk
Weight gain	Cardiac disorders	EG0002 events2 affected404 at risk EG0010 events0 affected405 at risk
Fatigue	Cardiac disorders	EG0001 events1 affected404 at risk EG0010 events0 affected405 at risk
Endocrine	Endocrine disorders	EG00013 events12 affected404 at risk EG0016 events4 affected405 at risk
Cancer	General disorders	EG0005 events5 affected404 at risk EG00113 events10 affected405 at risk
Traumatic injury	General disorders	EG00012 events11 affected404 at risk EG0014 events4 affected405 at risk
Headache	Nervous system disorders	EG0000 events0 affected404 at risk EG0014 events3 affected405 at risk
Hepatic	Hepatobiliary disorders	EG0002 events1 affected404 at risk EG0012 events2 affected405 at risk
Fatigue	General disorders	EG0003 events3 affected404 at risk EG0010 events0 affected405 at risk
Device related	Cardiac disorders	EG0006 events6 affected404 at risk EG00110 events9 affected405 at risk

Other Adverse Events

Term	Organ System	Statistical Information
Worsening heart failure	Cardiac disorders	EG00032 events29 affected404 at risk EG00134 events29 affected405 at risk
Atrial arrhythmia	Cardiac disorders	EG00044 events39 affected404 at risk EG00143 events35 affected405 at risk
Ventricular arrhythmia	Cardiac disorders	EG00039 events33 affected404 at risk EG00129 events25 affected405 at risk
Chest pain	Cardiac disorders	EG00021 events20 affected404 at risk EG00132 events29 affected405 at risk
Dyspnea	Cardiac disorders	EG00027 events20 affected404 at risk EG00132 events30 affected405 at risk
Hypotension	Cardiac disorders	EG00028 events27 affected404 at risk EG00130 events27 affected405 at risk
Dizziness	Cardiac disorders	EG00025 events21 affected404 at risk EG00115 events14 affected405 at risk
Edema	Cardiac disorders	EG00023 events21 affected404 at risk EG00116 events15 affected405 at risk
Non-cardiovascular	General disorders	EG000602 events203 affected404 at risk EG001548 events201 affected405 at risk
Implant Procedure	Surgical and medical procedures	EG00033 events31 affected404 at risk EG00146 events41 affected405 at risk
ICD lead	Cardiac disorders	EG00034 events28 affected404 at risk EG0016 events6 affected405 at risk
Lead for left ventricular pacing	Cardiac disorders	EG00055 events49 affected404 at risk EG00111 events10 affected405 at risk

ID	Term
D047548	Defibrillators
D004566	Electrodes
D055615	Electrical Equipment and Supplies
D004864	Equipment and Supplies
D004567	Electrodes, Implanted
D019736	Prostheses and Implants
D002304	Cardiac Pacing, Artificial
D004599	Electric Stimulation Therapy
D013812	Therapeutics

ID	Title	Description
BG000	CRT=ON	Cardiac Resynchronization Therapy activated.
BG001	CRT=OFF	Cardiac Resynchronization Therapy deactivated.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	CRT=ON	Cardiac Resynchronization Therapy activated.	45	404	259	404	300	404
EG001	CRT=OFF	Cardiac Resynchronization Therapy deactivated.	26	405	221	405	274	405

ID	Term
D017147	Defibrillators, Implantable
D058406	Cardiac Resynchronization Therapy