Atrial Fibrillation, Congestive Heart Failure
Conditions
Keywords
atrial fibrillation, AV node ablation, pacemaker, congestive heart failure
Brief summary
The purpose of this study is to demonstrate the safety and effectiveness of biventricular pacing over conventional right ventricular pacing in patients with persistent or permanent, symptomatic atrial fibrillation undergoing atrioventricular (AV) node ablation and permanent pacing therapy.
Detailed description
This study is a multi-center, prospective, randomized, blinded trial. The study will consist of approximately 265 patients who require treatment of persistent or permanent, symptomatic atrial fibrillation by atrioventricular (AV) node ablation and permanent pacing therapy i.e. Ablate and Pace therapy. All patients enrolled into the clinical study will be randomly assigned to one of three groups using a randomization ratio of 2:2:1. Patients will be assigned to receive either biventricular (biV) pacing with CLS-based rate adaptive pacing using the legally marketed Protos DR/CLS (Group 1), or biventricular pacing with accelerometer-based rate adaptive pacing using the Stratos LV (Group 2), or right ventricular (RV) pacing with accelerometer-based rate adaptive pacing using the Stratos LV (Group 3). Patients in all three groups will be implanted with legally marketed right and left ventricular pacing leads. The patients, the core lab used to interpret the echocardiographic data and the Clinical Events Committee adjudicating crossover, patient death and congestive heart failure (CHF) hospitalizations will be blinded to the randomization assignment.
Interventions
DEVICEProtos DR/CLS and Stratos LV CRT pacemakers
Protos DR/CLS is a dual chamber pacemaker with CLS rate adaption, Stratos LV is a biventricular pacemaker with accelerometer based rate adaption
Sponsors
Biotronik, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meet the indications for therapy * Persistent, symptomatic AF with poorly controlled rapid ventricular rates or permanent, symptomatic AF with poorly controlled rapid ventricular rates. * Eligible for AV nodal ablation and permanent pacemaker implantation * NYHA Class II or III heart failure * Age ≥ 18 years * Understand the nature of the procedure * Ability to tolerate the surgical procedure required for implantation * Give informed consent * Able to complete all testing required by the clinical protocol * Available for follow-up visits on a regular basis at the investigational site
Exclusion criteria
* Meet one or more of the contraindications * Have a life expectancy of less than six months * Expected to receive heart transplantation within six months * Enrolled in another cardiovascular or pharmacological clinical investigation * Patients with an ICD, or being considered for an ICD * Patients with previously implanted biventricular pacing systems * Patients with previously implanted single or dual chamber pacing system with \> 50% documented ventricular pacing * Patients with previous AV node ablation * Six-minute walk test distance greater than 450 meters * Any condition preventing the patient from being able to perform required testing * Presence of another life-threatening, underlying illness separate from their cardiac disorder * Conditions that prohibit placement of any of the lead systems
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Percentage Improvement From Baseline of the 6-minute Walk Test Distance and Minnesota Living With Heart Failure Quality of Life Score at 6-months | Change from baseline to six months post-procedure | Combined, average percentage improvement in 6-minute walk test distance and Minnessota Living With Heart Failure Quality of Life score from baseline to 6-month follow-up for the Protos DR/CLS (Group 1) and Stratos LV (Group 2) compared with the active control (Group 3). The 6-minute walk test is a test that measure how far a patient can walk in 6 minutes in a standardized walking course. Percent Change (0% (worst)-100% (best)) |
| Number of Participants Free of System-related Complications (Related to the Device, Leads, or Implant Procedure) at 6 Months Post-procedure | At six months post-procedure | Complication-free rate was evaluated in an equivalence (non-inferiority) format compared to a target of 85% minus delta (10%), where delta is the clinically significant difference for establishing equivalence. This endpoint evaluated system-related complications. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Ejection Fraction | Change from baseline to six months post-procedure | — |
| Changes in New York Heart Association (NYHA) Classification | Change from baseline to six months post-procedure | The purpose is to evaluate the change in the participant's NYHA classification. There are four NYHA classes: Class I: Patients 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: Patients 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: Patients 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: Patients 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. |
| Percentage of Patients With Congestive Heart Failure (CHF) Related Hospitalizations | At six months post-procedure | — |
| Mortality Rate | At six months post-procedure | — |
| Change in Six-minute Walk Test | Change from baseline to 6 months post-procedure | — |
| Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Mass | Change from baseline to six months post-procedure | — |
| Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Systolic Volume | Change from baseline to six months post-procedure | — |
| Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Diastolic Volume | Change from baseline to six months post-procedure | — |
| Cardiac Remodeling Assessments by Echocardiography - Change in Left Atrial Volume | Change from baseline to six months post-procedure | — |
| Change in Quality Of Life (QOL) Score Over 6 Months Calculated as QOL Score at Baseline - QOL Score at 6 Months | Change from baseline to six months post-procedure | 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. This outcome was calculated as QOL score at baseline minus QOL score at 6 months. Therefore, a positive change in QOL score represents an improvement in quality of life, while a negative change in QOL score represents a worsening. |
Countries
United States
Participant flow
Recruitment details
A total of 153 patients were enrolled at 22 clinical sites from December 9, 2004 (the first implant of the study) through May 12, 2008.
Pre-assignment details
No patients were excluded before assigment to groups. A total of 27 patients did not receive a device implant due to withdrawal of consent, inelegibility after randomization and unability to implant the LV lead.
Participants by arm
| Arm | Count |
|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) Patients are implanted with a Protos CLS device, using the atrial port of the device for the left ventricular lead and the ventricular port for the ventricular lead to provide biV pacing. CLS is activated for rate adaptation. | 58 |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) Patients are implanted with a Stratos LV device, with the atrial port plugged and the left ventricular port for the left ventricular lead and the right ventricular port for the right ventricular lead to provide biV pacing. The acceleromer is activated for rate adaptation. | 61 |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) Patients are implanted with a Stratos LV device, with the atrial port plugged and the left ventricular port for the left ventricular lead and the right ventricular port for the right ventricular lead to provide biV pacing. The device is programmed to right ventricular pacing only. The acceleromer is activated for rate adaptation. | 34 |
| Total | 153 |
Baseline characteristics
| Characteristic | biV-pacing With CLS Rate Adaption (Protos CLS) | biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Total |
|---|---|---|---|---|
| Age, Continuous | 74.1 years STANDARD_DEVIATION 8.4 | 72.7 years STANDARD_DEVIATION 7.8 | 72.3 years STANDARD_DEVIATION 8.2 | 73.1 years STANDARD_DEVIATION 8.1 |
| Region of Enrollment Canada | 1 participants | 2 participants | 1 participants | 4 participants |
| Region of Enrollment United States | 57 participants | 59 participants | 33 participants | 149 participants |
| Sex: Female, Male Female | 34 Participants | 39 Participants | 17 Participants | 90 Participants |
| Sex: Female, Male Male | 24 Participants | 22 Participants | 17 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 153 |
| other Total, other adverse events | 102 / 153 |
| serious Total, serious adverse events | 58 / 153 |
Outcome results
Primary
Average Percentage Improvement From Baseline of the 6-minute Walk Test Distance and Minnesota Living With Heart Failure Quality of Life Score at 6-months
Combined, average percentage improvement in 6-minute walk test distance and Minnessota Living With Heart Failure Quality of Life score from baseline to 6-month follow-up for the Protos DR/CLS (Group 1) and Stratos LV (Group 2) compared with the active control (Group 3). The 6-minute walk test is a test that measure how far a patient can walk in 6 minutes in a standardized walking course. Percent Change (0% (worst)-100% (best))
Time frame: Change from baseline to six months post-procedure
Population: Patients included in this analysis are those patients with complete six minute walk test and Quality of Life data at both baseline and the six-month follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Average Percentage Improvement From Baseline of the 6-minute Walk Test Distance and Minnesota Living With Heart Failure Quality of Life Score at 6-months | 40.1 Percent Change | Standard Error 5.7 |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Average Percentage Improvement From Baseline of the 6-minute Walk Test Distance and Minnesota Living With Heart Failure Quality of Life Score at 6-months | 42.5 Percent Change | Standard Error 8.9 |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Average Percentage Improvement From Baseline of the 6-minute Walk Test Distance and Minnesota Living With Heart Failure Quality of Life Score at 6-months | 31.5 Percent Change | Standard Error 9 |
p-value: 0.437t-test, 2 sided
p-value: 0.405t-test, 2 sided
Primary
Number of Participants Free of System-related Complications (Related to the Device, Leads, or Implant Procedure) at 6 Months Post-procedure
Complication-free rate was evaluated in an equivalence (non-inferiority) format compared to a target of 85% minus delta (10%), where delta is the clinically significant difference for establishing equivalence. This endpoint evaluated system-related complications.
Time frame: At six months post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Number of Participants Free of System-related Complications (Related to the Device, Leads, or Implant Procedure) at 6 Months Post-procedure | 49 Participants |
p-value: 0.0596t-test, 1 sided
Primary
Number of Participants Free of System-related Complications (Related to the Device, Leads, or Implant Procedure) at 6 Months Post-procedure
Complication-free rate was evaluated in an equivalence (non-inferiority) format compared to a target of 85% minus delta (10%), where delta is the clinically significant difference for establishing equivalence. This endpoint evaluated system-related complications. All Stratos systems (in both the biV and RV pacing arms) were evaluated together as pre-specified in the protocol.
Time frame: At six months post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Number of Participants Free of System-related Complications (Related to the Device, Leads, or Implant Procedure) at 6 Months Post-procedure | 84 Participants |
p-value: 0.0009t-test, 1 sided
Secondary
Cardiac Remodeling Assessments by Echocardiography - Change in Left Atrial Volume
Time frame: Change from baseline to six months post-procedure
Population: Subjects with paired baseline and 6-month echocardiography data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Atrial Volume | -3.2 mL | Standard Error 2.8 |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Atrial Volume | -1.1 mL | Standard Error 2.8 |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Atrial Volume | 13.7 mL | Standard Error 6 |
p-value: 0.005t-test, 2 sided
p-value: 0.014t-test, 2 sided
Secondary
Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Ejection Fraction
Time frame: Change from baseline to six months post-procedure
Population: Subjects with paired baseline and 6-month echocardiography data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Ejection Fraction | 3.1 percent | Standard Error 1.3 |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Ejection Fraction | 3.4 percent | Standard Error 0.9 |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Ejection Fraction | -2.6 percent | Standard Error 2.6 |
p-value: 0.03t-test, 2 sided
p-value: 0.006t-test, 2 sided
Secondary
Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Diastolic Volume
Time frame: Change from baseline to six months post-procedure
Population: Subjects with paired baseline and 6-month echocardiography data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Diastolic Volume | -10.1 mL | Standard Error 3.5 |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Diastolic Volume | -7.1 mL | Standard Error 4 |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Diastolic Volume | 9.5 mL | Standard Error 8.2 |
p-value: 0.039t-test, 2 sided
p-value: 0.047t-test, 2 sided
Secondary
Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Systolic Volume
Time frame: Change from baseline to six months post-procedure
Population: Subjects with paired baseline and 6-month echocardiography data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Systolic Volume | -7.7 mL | Standard Error 1.7 |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Systolic Volume | -5.9 mL | Standard Error 2.1 |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Systolic Volume | 8.7 mL | Standard Error 4.6 |
p-value: <0.001t-test, 2 sided
p-value: 0.001t-test, 2 sided
Secondary
Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Mass
Time frame: Change from baseline to six months post-procedure
Population: Subjects with paired baseline and 6-month echocardiography data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Mass | -1.2 grams | Standard Error 5.7 |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Mass | -14.5 grams | Standard Error 8.3 |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Mass | 25.1 grams | Standard Error 10.5 |
p-value: 0.02t-test, 2 sided
p-value: 0.008t-test, 2 sided
Secondary
Change in Quality Of Life (QOL) Score Over 6 Months Calculated as QOL Score at Baseline - QOL Score at 6 Months
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. This outcome was calculated as QOL score at baseline minus QOL score at 6 months. Therefore, a positive change in QOL score represents an improvement in quality of life, while a negative change in QOL score represents a worsening.
Time frame: Change from baseline to six months post-procedure
Population: Subjects with paired baseline and 6-month QOL data. A positive score represents improvement from baseline to 6-months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Change in Quality Of Life (QOL) Score Over 6 Months Calculated as QOL Score at Baseline - QOL Score at 6 Months | 28.9 units on a scale | Standard Error 3.9 |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Change in Quality Of Life (QOL) Score Over 6 Months Calculated as QOL Score at Baseline - QOL Score at 6 Months | 25.2 units on a scale | Standard Error 3.2 |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Change in Quality Of Life (QOL) Score Over 6 Months Calculated as QOL Score at Baseline - QOL Score at 6 Months | 24.5 units on a scale | Standard Error 6.1 |
Secondary
Change in Six-minute Walk Test
Time frame: Change from baseline to 6 months post-procedure
Population: Subjects with paired baseline and 6-month six-minute walk test data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Change in Six-minute Walk Test | 48.1 Meters | Standard Error 13.2 |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Change in Six-minute Walk Test | 49.3 Meters | Standard Error 12.9 |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Change in Six-minute Walk Test | 54.5 Meters | Standard Error 20.9 |
Secondary
Changes in New York Heart Association (NYHA) Classification
The purpose is to evaluate the change in the participant's NYHA classification. There are four NYHA classes: Class I: Patients 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: Patients 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: Patients 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: Patients 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.
Time frame: Change from baseline to six months post-procedure
Population: Subjects with paired baseline and 6-month NYHA classification data. The outcome of Improved at least 1 Class represents a numerically higher NYHA class at baseline than at 6 months (e.g. NYHA class III at baseline changed to NYHA class II at 6 months).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Changes in New York Heart Association (NYHA) Classification | Improved at least 1 Class | 24 Participants |
| biV-pacing With CLS Rate Adaption (Protos CLS) | Changes in New York Heart Association (NYHA) Classification | No change | 17 Participants |
| biV-pacing With CLS Rate Adaption (Protos CLS) | Changes in New York Heart Association (NYHA) Classification | Worsened at least 1 Class | 3 Participants |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Changes in New York Heart Association (NYHA) Classification | Improved at least 1 Class | 26 Participants |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Changes in New York Heart Association (NYHA) Classification | No change | 17 Participants |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Changes in New York Heart Association (NYHA) Classification | Worsened at least 1 Class | 2 Participants |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Changes in New York Heart Association (NYHA) Classification | Worsened at least 1 Class | 2 Participants |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Changes in New York Heart Association (NYHA) Classification | No change | 11 Participants |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Changes in New York Heart Association (NYHA) Classification | Improved at least 1 Class | 9 Participants |
Secondary
Mortality Rate
Time frame: At six months post-procedure
Population: Subjects enrolled
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Mortality Rate | 1.7 percentage of participants analyzed |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Mortality Rate | 11.5 percentage of participants analyzed |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Mortality Rate | 5.9 percentage of participants analyzed |
Secondary
Percentage of Patients With Congestive Heart Failure (CHF) Related Hospitalizations
Time frame: At six months post-procedure
Population: Subjects successfully implanted with investigational system.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| biV-pacing With CLS Rate Adaption (Protos CLS) | Percentage of Patients With Congestive Heart Failure (CHF) Related Hospitalizations | 20 percentage of participants analyzed |
| biV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Percentage of Patients With Congestive Heart Failure (CHF) Related Hospitalizations | 13 percentage of participants analyzed |
| RV Pacing With Accelerometer Based Rate Adaption (Stratos LV) | Percentage of Patients With Congestive Heart Failure (CHF) Related Hospitalizations | 16 percentage of participants analyzed |