Trial Outcomes & Findings for Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT) (NCT NCT00683696)

Last Updated: 2018-01-17

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

1680 participants

Primary outcome 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

Results posted on

2018-01-17

Participant Flow

After enrollment, baseline eligibility criteria were assessed (e.g. ventricular dyssynchrony, NYHA, QRS width, etc.) to qualify for implant. 1680 subjects were enrolled. 825 subjects did not qualify for implant and were exited from the study. 855 subjects qualified for implant. 821 subjects were successfully implanted. 809 subjects were randomized.

Participant milestones

Participant milestones
Measure	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.	CRT=OFF Cardiac Resynchronization Therapy deactivated. Subject implanted with BIOTRONIK Lumax HF-T CRT-D system with ICD back-up enabled and randomized to CRT=OFF.
Overall Study STARTED	404	405
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	404	405

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	CRT=OFF Cardiac Resynchronization Therapy deactivated. Subject implanted with BIOTRONIK Lumax HF-T CRT-D system with ICD back-up enabled and randomized to CRT=OFF.
Overall Study Withdrawn due to study closure	337	338
Overall Study Withdrawn prior to study closure	13	28
Overall Study Lost to Follow-up	5	6
Overall Study Vital status follow-up only	3	3
Overall Study Death	46	30

Baseline Characteristics

Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CRT=ON n=404 Participants Cardiac Resynchronization Therapy activated.	CRT=OFF n=405 Participants Cardiac Resynchronization Therapy deactivated.	Total n=809 Participants Total of all reporting groups
Age, Continuous	57.6 years STANDARD_DEVIATION 12.9 • n=5 Participants	58.3 years STANDARD_DEVIATION 12.6 • n=7 Participants	58.0 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex: Female, Male Female	110 Participants n=5 Participants	114 Participants n=7 Participants	224 Participants n=5 Participants
Sex: Female, Male Male	294 Participants n=5 Participants	291 Participants n=7 Participants	585 Participants n=5 Participants
Region of Enrollment Portugal	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment United States	196 participants n=5 Participants	198 participants n=7 Participants	394 participants n=5 Participants
Region of Enrollment Spain	18 participants n=5 Participants	18 participants n=7 Participants	36 participants n=5 Participants
Region of Enrollment Austria	6 participants n=5 Participants	8 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Israel	18 participants n=5 Participants	16 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment United Kingdom	19 participants n=5 Participants	18 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment Switzerland	11 participants n=5 Participants	11 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Italy	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment France	10 participants n=5 Participants	11 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment Czech Republic	12 participants n=5 Participants	11 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment Canada	13 participants n=5 Participants	14 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Poland	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Belgium	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Australia	12 participants n=5 Participants	11 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment Denmark	24 participants n=5 Participants	23 participants n=7 Participants	47 participants n=5 Participants
Region of Enrollment Germany	41 participants n=5 Participants	41 participants n=7 Participants	82 participants n=5 Participants
Region of Enrollment Netherlands	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants

PRIMARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	CRT=ON n=404 Participants Cardiac Resynchronization Therapy activated.	CRT=OFF n=405 Participants Cardiac Resynchronization Therapy deactivated.
Composite Primary Endpoint: Number of Subjects With First Hospitalization for Worsening Heart Failure or Death	116 participants	102 participants

PRIMARY outcome

Timeframe: 6 months

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

The primary safety endpoint will evaluate the complication-free rate of the Lumax HF-T CRT-D devices in the narrow QRS subject population.

Outcome measures

Outcome measures
Measure	CRT=ON n=855 Participants Cardiac Resynchronization Therapy activated.	CRT=OFF Cardiac Resynchronization Therapy deactivated.
Number of Subjects That Underwent Implant Attempt Without System- or Implant-Related Complications (Complication-Free)	766 participants	—

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	CRT=ON n=404 Participants Cardiac Resynchronization Therapy activated.	CRT=OFF n=405 Participants Cardiac Resynchronization Therapy deactivated.
Rate of Hospitalizations for Worsening Heart Failure (Hospitalizations Per Subject-year)	0.36 Hospitalizations per subj-yr	0.28 Hospitalizations per subj-yr

SECONDARY outcome

Timeframe: 6 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	CRT=ON n=347 Participants Cardiac Resynchronization Therapy activated.	CRT=OFF n=338 Participants Cardiac Resynchronization Therapy deactivated.
New York Heart Association (NYHA) Classification Change Improved at least 1 Class	213 Participants	185 Participants
New York Heart Association (NYHA) Classification Change No Change	116 Participants	141 Participants
New York Heart Association (NYHA) Classification Change Deteriorated at least 1 Class	18 Participants	12 Participants

SECONDARY outcome

Timeframe: Changes between baseline and 6 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	CRT=ON n=333 Participants Cardiac Resynchronization Therapy activated.	CRT=OFF n=330 Participants Cardiac Resynchronization Therapy deactivated.
Change in Quality of Life (QOL) Scores From Baseline to 6-Month Follow-up	-12.1 units on a scale Standard Deviation 21.9	-13.5 units on a scale Standard Deviation 21.4

SECONDARY outcome

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

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

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.

Outcome measures

Outcome measures
Measure	CRT=ON n=163 Participants Cardiac Resynchronization Therapy activated.	CRT=OFF n=163 Participants Cardiac Resynchronization Therapy deactivated.
Composite Score of Death, Hospitalization for Worsening Heart Failure and Change in Quality of Life (QOL)	-1.6 Composite score Standard Deviation 1.9	-1.5 Composite score Standard Deviation 1.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	CRT=ON n=404 Participants Cardiac Resynchronization Therapy activated.	CRT=OFF n=405 Participants Cardiac Resynchronization Therapy deactivated.
Number of Subjects With All-cause Mortality	45 Participants	26 Participants

Adverse Events

CRT=ON

Serious events: 259 serious events

Other events: 300 other events

Deaths: 45 deaths

CRT=OFF

Serious events: 221 serious events

Other events: 274 other events

Deaths: 26 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	CRT=ON n=404 participants at risk Cardiac Resynchronization Therapy activated.	CRT=OFF n=405 participants at risk Cardiac Resynchronization Therapy deactivated.
Cardiac disorders Worsening heart failure	7.2% 29/404 • Number of events 32 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	7.2% 29/405 • Number of events 34 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.
Cardiac disorders Atrial arrhythmia	9.7% 39/404 • Number of events 44 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	8.6% 35/405 • Number of events 43 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.
Cardiac disorders Ventricular arrhythmia	8.2% 33/404 • Number of events 39 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	6.2% 25/405 • Number of events 29 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.
Cardiac disorders Chest pain	5.0% 20/404 • Number of events 21 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	7.2% 29/405 • Number of events 32 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.
Cardiac disorders Dyspnea	5.0% 20/404 • Number of events 27 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	7.4% 30/405 • Number of events 32 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.
Cardiac disorders Hypotension	6.7% 27/404 • Number of events 28 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	6.7% 27/405 • Number of events 30 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.
Cardiac disorders Dizziness	5.2% 21/404 • Number of events 25 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	3.5% 14/405 • Number of events 15 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.
Cardiac disorders Edema	5.2% 21/404 • Number of events 23 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	3.7% 15/405 • Number of events 16 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.
General disorders Non-cardiovascular	50.2% 203/404 • Number of events 602 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	49.6% 201/405 • Number of events 548 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.
Surgical and medical procedures Implant Procedure	7.7% 31/404 • Number of events 33 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	10.1% 41/405 • Number of events 46 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.
Cardiac disorders ICD lead	6.9% 28/404 • Number of events 34 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	1.5% 6/405 • Number of events 6 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.
Cardiac disorders Lead for left ventricular pacing	12.1% 49/404 • Number of events 55 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.	2.5% 10/405 • Number of events 11 • Study duration from date of implant to date of study exit, with a mean implant duration of 1.7 years Subjects could have more than one event. Other adverse event data includes data from non-serious adverse events.

Additional Information

Kelly Mohr

Biotronik, Inc.

Phone: 800-547-0394

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place