Adaptive Cardiac Resynchronization Therapy Study

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00980057

Acronym

aCRT

Enrollment

522

Registered

2009-09-18

Start date

2009-10-01

Completion date

2012-03-08

Last updated

2018-10-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure

Brief summary

The purpose of this study is to demonstrate the AdaptivCRT algorithm is at least as good as manual echo based optimization in regard to patient outcomes and cardiac performance

Detailed description

The trial has 3 primary end points: * to demonstrate that over 6-month follow-up, the proportion of the patients improved in the aCRT arm is at least as high as in the Echo arm * to demonstrate that cardiac function is similar when using aCRT versus echo-optimized settings * to demonstrate that aCRT does not result in inappropriate AV or VV delay settings

Interventions

DEVICEAdaptive CRT (aCRT)

Adaptive CRT (aCRT) is an algorithm, which provides ambulatory adjustment of pacing configuration (LV-only or BiV) and AV and VV delays based on periodic automatic evaluation of electrical conduction to optimize cardiac function

DEVICEEcho

Standard BiV pacing with settings optimized using a standardized echocardiographic protocol

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Subject is willing to sign and date the study Informed Consent form * Subject is at least 18 years of age (or older, if required by local law) * Subject is expected to remain available for at least six months of follow-up visits * Subject is indicated for a study device that will be implanted within 30 days after signing the Informed Consent form * Subject has an intrinsic QRS duration greater than or equal to 120 milliseconds (documented within 30 days prior to enrollment) * Subject has a left ventricular ejection fraction less than or equal to 35 percent (method per physician discretion) (documented within 180 days prior to enrollment) * Subject is diagnosed with New York Heart Association (NYHA) class III or IV (within 30 days prior to enrollment) despite optimal medical therapy which is defined as: ACE-inhibitor (Angiotensin-Converting Enzyme) or Angiotensin II Receptor Blocker (ARB), if tolerated, for at least one month prior to implant, AND beta-blocker for at least three months preceding implant, if tolerated, and stable for one month, OR subject has an urgent medical need for an implantable cardioverter defibrillator (ICD) that precludes waiting the one or three months for the medication requirements for ACE inhibitor, ARB or beta-blocker

Exclusion criteria

* Subject has chronic (permanent) atrial arrhythmias for which pharmacological therapy and/or cardioversion have been unsuccessful or have not been attempted * Subject has existing CRT system * Subject has non-intact or unstable leads * Subject has medical conditions that would limit study participation (per physician discretion) * Subject is enrolled in one or more concurrent studies that would confound the study results of this study as determined by Medtronic * Subject has unstable angina, or experienced an acute myocardial infarction (MI) or received coronary artery revascularization (CABG) or coronary angioplasty (PTCA) (documented within 30 days prior to enrollment) * Subject has a mechanical right heart valve or is scheduled to undergo valve repair or valve replacement during the course of the study * Subject is post-heart transplant (subjects on the heart transplant list for the first time are not excluded) * Subject has a limited life expectancy that would not allow completion of the 6 month visit * Subject is pregnant (In the United States, all women of child-bearing potential must undergo a pregnancy test within seven days prior to aCRT download into device) * Subject meets the

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Patients With Improved Heart Failure Outcomes Clinical Composite Score	randomization to six month visit	Patients considered worsened if they died, were hospitalized with worsening heart failure (HF), crossed over to other arm, demonstrated worsening in New York Heart Association (NYHA) functional class, or reported moderately/markedly worse on 'patient global assessment' compared to before CRT implant. Patients are improved if they are not worsened and have an improved NYHA or reported moderately/markedly improved on the 'patient global assessment' compared to before CRT implant Global assessment question for the patient: Specifically in reference to your heart failure symptoms, how do you feel today as compared to how you felt before your CRT system was implanted? O Markedly improved O Moderately improved O Mildly improved O No change O Slightly worse O Moderately worse O Markedly worse
Correlation Between Aortic Velocity Time Integral (AoVTI) at Adaptive CRT and Echo-optimized Device Settings	randomization visit and six month visit	Correlation between aortic velocity time integral (AoVTI) at Adaptive CRT and echo-optimized device settings. AoVTI is an echocardiographic representative of stroke volume and cardiac performance.
Percentage of Patients With a Safety Event (Inappropriate AV or VV Delay Settings Related to the aCRT Feature)	randomization to 6 months post randomization	For each subject, the Adaptive CRT-determined AV and VV delay settings from randomization up to 183-days post-randomization were evaluated to identify any period of 28-days with a wide delay range (\>60 ms)

Secondary

Measure	Time frame	Description
Change in New York Heart Association (NYHA) Classification	baseline to six month visit	The New York Heart Association (NYHA) Functional Classification places patients in one of four categories based on how much they are limited during physical activity. Class - Patient Symptoms I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath). II- Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). III- Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. IV- Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.
Right Ventricular Pacing Percentage	implant to six months post randomization	The percentage of time the right ventricle is paced by the device
Change in Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire (MLWHF)	baseline to six month visit	The MLWHF is a 21 question survey. Scores range from 0-105, with lower scores indicating better health.
Change in Distance Walked During the Six Minute Hall Walk	baseline to six month visit	—
Change in Left Ventricular End Systolic Volume Index (LVESVi)	baseline to six month visit	Change in left ventricular end systolic volume index (LVESVi).
Change in Left Ventricular Ejection Fraction (LVEF)	baseline to six month visit	—

Countries

Australia, Austria, Belgium, Canada, Denmark, Germany, Greece, Hong Kong, Hungary, Italy, Japan, Netherlands, Norway, Russia, Saudi Arabia, Serbia, Spain, Sweden, United States

Participant flow

Pre-assignment details

Total number of: * 522 pts enrolled, 1 exit * 521 pts with baseline information, 16 exits * 505 pts of which 14 unsuccessful implants and 491 successful implants, 12 exits and 1 death * 478 randomized (318 to aCRT, 160 to control)

Participants by arm

Arm	Count
Adaptive CRT (aCRT) Pacing Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	318
Standard Biventricular Pacing Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)	160
Total	478

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	1
Overall Study	Death	13	3
Overall Study	Lost to Follow-up	1	0
Overall Study	Physician Decision	4	0
Overall Study	Withdrawal by Subject	1	1

Baseline characteristics

Characteristic	Standard Biventricular Pacing	Total	Adaptive CRT (aCRT) Pacing
Age, Continuous	66.2 years STANDARD_DEVIATION 9.7	65.7 years STANDARD_DEVIATION 10.7	65.4 years STANDARD_DEVIATION 11.2
Race/Ethnicity, Customized Asian	3 Participants	11 Participants	8 Participants
Race/Ethnicity, Customized Black or African American	6 Participants	35 Participants	29 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 Participants	18 Participants	13 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	1 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized Not available	5 Participants	12 Participants	7 Participants
Race/Ethnicity, Customized Other race	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Two or more races	1 Participants	4 Participants	3 Participants
Race/Ethnicity, Customized White or Caucasian	139 Participants	396 Participants	257 Participants
Region of Enrollment Australia	12 participants	30 participants	18 participants
Region of Enrollment Austria	2 participants	7 participants	5 participants
Region of Enrollment Belgium	3 participants	9 participants	6 participants
Region of Enrollment Canada	8 participants	25 participants	17 participants
Region of Enrollment Denmark	7 participants	18 participants	11 participants
Region of Enrollment Germany	14 participants	45 participants	31 participants
Region of Enrollment Hong Kong	1 participants	3 participants	2 participants
Region of Enrollment Italy	2 participants	5 participants	3 participants
Region of Enrollment Japan	2 participants	6 participants	4 participants
Region of Enrollment Netherlands	5 participants	16 participants	11 participants
Region of Enrollment Norway	3 participants	10 participants	7 participants
Region of Enrollment Russia	0 participants	1 participants	1 participants
Region of Enrollment Saudi Arabia	1 participants	2 participants	1 participants
Region of Enrollment Serbia	10 participants	33 participants	23 participants
Region of Enrollment Spain	0 participants	1 participants	1 participants
Region of Enrollment Sweden	2 participants	4 participants	2 participants
Region of Enrollment United States	87 participants	263 participants	176 participants
Sex: Female, Male Female	51 Participants	148 Participants	97 Participants
Sex: Female, Male Male	109 Participants	330 Participants	221 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	35 / 318	19 / 160
other Total, other adverse events	50 / 318	34 / 160
serious Total, serious adverse events	158 / 318	86 / 160

Outcome results

Primary

Correlation Between Aortic Velocity Time Integral (AoVTI) at Adaptive CRT and Echo-optimized Device Settings

Correlation between aortic velocity time integral (AoVTI) at Adaptive CRT and echo-optimized device settings. AoVTI is an echocardiographic representative of stroke volume and cardiac performance.

Time frame: randomization visit and six month visit

Population: Concordance correlations have been calculated between AoVTI at Adaptive CRT AV and VV settings vs. echo-optimized AV and VV settings at randomization and 6 M. Paired AoVTI measurements were used for concordance correlation analysis, where each subject served as his/her own control. AoVTI was not obtained at both settings for 79 patients.

Arm	Measure	Value (NUMBER)
Adaptive CRT (aCRT) Pacing	Correlation Between Aortic Velocity Time Integral (AoVTI) at Adaptive CRT and Echo-optimized Device Settings	0.93 Concordance correlation coefficient

p-value: <0.0001t-test, 1 sided

Primary

Percentage of Patients With a Safety Event (Inappropriate AV or VV Delay Settings Related to the aCRT Feature)

For each subject, the Adaptive CRT-determined AV and VV delay settings from randomization up to 183-days post-randomization were evaluated to identify any period of 28-days with a wide delay range (\>60 ms)

Time frame: randomization to 6 months post randomization

Population: 17 participants did not have data available for analysis of this endpoint.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Adaptive CRT (aCRT) Pacing	Percentage of Patients With a Safety Event (Inappropriate AV or VV Delay Settings Related to the aCRT Feature)	0 Participants

Primary

Percentage of Patients With Improved Heart Failure Outcomes Clinical Composite Score

Patients considered worsened if they died, were hospitalized with worsening heart failure (HF), crossed over to other arm, demonstrated worsening in New York Heart Association (NYHA) functional class, or reported moderately/markedly worse on 'patient global assessment' compared to before CRT implant. Patients are improved if they are not worsened and have an improved NYHA or reported moderately/markedly improved on the 'patient global assessment' compared to before CRT implant Global assessment question for the patient: Specifically in reference to your heart failure symptoms, how do you feel today as compared to how you felt before your CRT system was implanted? O Markedly improved O Moderately improved O Mildly improved O No change O Slightly worse O Moderately worse O Markedly worse

Time frame: randomization to six month visit

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Adaptive CRT (aCRT) Pacing	Percentage of Patients With Improved Heart Failure Outcomes Clinical Composite Score	234 Participants
Standard Biventricular Pacing	Percentage of Patients With Improved Heart Failure Outcomes Clinical Composite Score	114 Participants

p-value: 0.0002Farrington-Manning test of two ind. prop

Secondary