AVAIL: Investigational Device Exemption (IDE) Study for the Approval of Closed Loop Stimulation (CLS) and Cardiac Resyncronization Pacing Therapies (CRT) for the Treatment of Atrial Fibrillation (AF) With Ablate and Pace

• Sponsor: Biotronik, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00356057
• Collaborator: (none)
• Enrollment: 153
• Locations: 10
• Arms: 3
• Duration (Months): 42
• Patients Per Site: 15.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation; Congestive Heart Failure	Device: Protos DR/CLS and Stratos LV CRT pacemakers	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 153 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: AVAIL CLS/CRT: AV-node Ablation With CLS and CRT Pacing Therapies for the Treatment of AF
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Biventricular pacing group with Closed Loop Stimulation rate adaptation (Protos CLS device)	Device: Protos 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; Other Names: Protos DR/CLS dual chamber pacemaker
Active Comparator: 2 Biventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Device: Protos 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; Other Names: Protos DR/CLS dual chamber pacemaker
Active Comparator: 3 Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Device: Protos 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; Other Names: Protos DR/CLS dual chamber pacemaker

Outcome Measures

Primary Outcome Measures

1. 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))

2. 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.

3. 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. All Stratos systems (in both the biV and RV pacing arms) were evaluated together as pre-specified in the protocol.

Secondary Outcome Measures

1. Change in Six-minute Walk Test [Change from baseline to 6 months post-procedure]

2. 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.

3. Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Ejection Fraction [Change from baseline to six months post-procedure]

4. 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.

5. Percentage of Patients With Congestive Heart Failure (CHF) Related Hospitalizations [At six months post-procedure]

6. Mortality Rate [At six months post-procedure]

7. Cardiac Remodeling Assessments by Echocardiography - Change in Left Atrial Volume [Change from baseline to six months post-procedure]

8. Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Mass [Change from baseline to six months post-procedure]

9. Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Systolic Volume [Change from baseline to six months post-procedure]

10. Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Diastolic Volume [Change from baseline to six months post-procedure]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States
2	Lake Charles Memorial	Lake Charles	Louisiana	United States
3	Caritas St. Elizabeth's Medical Center	Boston	Massachusetts	United States
4	St. Joseph Mercy	Ann Arbor	Michigan	United States
5	McLaren Heart Foundation	Lapeer	Michigan	United States
6	NYU Medical Center	New York	New York	United States
7	Aultman Hospital	Canton	Ohio	United States
8	Ohio State University	Columbus	Ohio	United States
9	Spartanburg Regional	Spartanburg	South Carolina	United States
10	Lone Star Arrhythmia	Amarillo	Texas	United States

Sponsors and Collaborators

• Biotronik, Inc.

Investigators

• Principal Investigator: Michael Orlov, MD, Caritas Elizabeth, Boston, MA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biotronik, Inc.
• ClinicalTrials.gov Identifier: NCT00356057
• Other Study ID Numbers: G040150
• First Posted: Jul 25, 2006
• Last Update Posted: Feb 27, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Biotronik, Inc.: atrial fibrillation; AV node ablation; pacemaker; congestive heart failure
• Additional relevant MeSH terms: Heart Failure; Atrial Fibrillation

Study Results

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 Detail	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.

Arm/Group Title	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)
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	58	61	34
IMPLANTED	49	52	25
COMPLETED	45	47	22
NOT COMPLETED	13	14	12

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	58	61	34	153
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.1 (8.4)	72.7 (7.8)	72.3 (8.2)	73.1 (8.1)
Sex: Female, Male (Count of Participants)
Female	34 58.6%	39 63.9%	17 50%	90 58.8%
Male	24 41.4%	22 36.1%	17 50%	63 41.2%
Region of Enrollment (participants) [Number]
United States	57 98.3%	59 96.7%	33 97.1%	149 97.4%
Canada	1 1.7%	2 3.3%	1 2.9%	4 2.6%

Outcome Measures

1. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	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)
Arm/Group Description	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.	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.	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.
Measure Participants	43	43	22
Mean (Standard Error) [Percent Change]	40.1 (5.7)	42.5 (8.9)	31.5 (9.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	biV Pacing With Accelerometer Based Rate Adaption (Stratos LV), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.437
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	biV-pacing With CLS Rate Adaption (Protos CLS), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.405
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Number of Participants Free of System-related Complications (Related to the Device, Leads, or Implant Procedure) at 6 Months Post-procedure
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Protos DR/CLS System
Arm/Group Description	Protos DR/CLS (biV pacing with CLS rate adaptation)
Measure Participants	58
Count of Participants [Participants]	49 84.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	biV-pacing With CLS Rate Adaption (Protos CLS)
	Comments
	Type of Statistical Test	Equivalence
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0596
	Comments
	Method	t-test, 1 sided
	Comments

3. Primary Outcome

Title	Number of Participants Free of System-related Complications (Related to the Device, Leads, or Implant Procedure) at 6 Months Post-procedure
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stratos LV System
Arm/Group Description	Stratos LV (biV or RV pacing groups with accelerometer based rate adaptation)
Measure Participants	95
Count of Participants [Participants]	84 144.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	biV-pacing With CLS Rate Adaption (Protos CLS)
	Comments
	Type of Statistical Test	Equivalence
	Comments	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.
Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	t-test, 1 sided
	Comments

4. Secondary Outcome

Title	Change in Six-minute Walk Test
Time Frame	Change from baseline to 6 months post-procedure

Outcome Measure Data

Analysis Population Description

Subjects with paired baseline and 6-month six-minute walk test data.

Arm/Group Title	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)
Arm/Group Description	Biventricular pacing group with Closed Loop Stimulation rate adaptation (Protos CLS device)	Biventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device)
Measure Participants	44	44	22
Mean (Standard Error) [Meters]	48.1 (13.2)	49.3 (12.9)	54.5 (20.9)

5. Secondary Outcome

Title	Change in Quality Of Life (QOL) Score Over 6 Months Calculated as QOL Score at Baseline - QOL Score at 6 Months
Description	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

Outcome Measure Data

Analysis Population Description

Subjects with paired baseline and 6-month QOL data. A positive score represents improvement from baseline to 6-months.

Arm/Group Title	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)
Arm/Group Description	Biventricular pacing group with Closed Loop Stimulation rate adaptation (Protos CLS device)	Biventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device)
Measure Participants	43	45	22
Mean (Standard Error) [units on a scale]	28.9 (3.9)	25.2 (3.2)	24.5 (6.1)

6. Secondary Outcome

Title	Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Ejection Fraction
Time Frame	Change from baseline to six months post-procedure

Outcome Measure Data

Analysis Population Description

Subjects with paired baseline and 6-month echocardiography data.

Arm/Group Title	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)
Arm/Group Description	Biventricular pacing group with Closed Loop Stimulation rate adaptation (Protos CLS device)	Biventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device)
Measure Participants	36	42	14
Mean (Standard Error) [percent]	3.1 (1.3)	3.4 (0.9)	-2.6 (2.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	biV-pacing With CLS Rate Adaption (Protos CLS), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	biV Pacing With Accelerometer Based Rate Adaption (Stratos LV), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Changes in New York Heart Association (NYHA) Classification
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	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)
Arm/Group Description	Biventricular pacing group with Closed Loop Stimulation rate adaptation (Protos CLS device)	Biventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device)
Measure Participants	44	45	22
Improved at least 1 Class	24 41.4%	26 42.6%	9 26.5%
No change	17 29.3%	17 27.9%	11 32.4%
Worsened at least 1 Class	3 5.2%	2 3.3%	2 5.9%

8. Secondary Outcome

Title	Percentage of Patients With Congestive Heart Failure (CHF) Related Hospitalizations
Time Frame	At six months post-procedure

Outcome Measure Data

Analysis Population Description

Subjects successfully implanted with investigational system.

Arm/Group Title	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)
Arm/Group Description	Biventricular pacing group with Closed Loop Stimulation rate adaptation (Protos CLS device)	Biventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device)
Measure Participants	49	52	25
Number [percentage of participants analyzed]	20 34.5%	13 21.3%	16 47.1%

9. Secondary Outcome

Title	Mortality Rate
Time Frame	At six months post-procedure

Outcome Measure Data

Analysis Population Description

Subjects enrolled

Arm/Group Title	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)
Arm/Group Description	Biventricular pacing group with CLS rate adaptation (Protos CLS device)	Biventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device)
Measure Participants	58	61	34
Number [percentage of participants analyzed]	1.7 2.9%	11.5 18.9%	5.9 17.4%

10. Secondary Outcome

Title	Cardiac Remodeling Assessments by Echocardiography - Change in Left Atrial Volume
Time Frame	Change from baseline to six months post-procedure

Outcome Measure Data

Analysis Population Description

Subjects with paired baseline and 6-month echocardiography data.

Arm/Group Title	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)
Arm/Group Description	Biventricular pacing group with Closed Loop Stimulation rate adaptation (Protos CLS device)	Biventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device)
Measure Participants	37	41	18
Mean (Standard Error) [mL]	-3.2 (2.8)	-1.1 (2.8)	13.7 (6.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	biV-pacing With CLS Rate Adaption (Protos CLS), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	biV Pacing With Accelerometer Based Rate Adaption (Stratos LV), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	t-test, 2 sided
	Comments

11. Secondary Outcome

Title	Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Mass
Time Frame	Change from baseline to six months post-procedure

Outcome Measure Data

Analysis Population Description

Subjects with paired baseline and 6-month echocardiography data.

Arm/Group Title	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)
Arm/Group Description	Biventricular pacing group with Closed Loop Stimulation rate adaptation (Protos CLS device)	Biventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device)
Measure Participants	41	45	19
Mean (Standard Error) [grams]	-1.2 (5.7)	-14.5 (8.3)	25.1 (10.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	biV-pacing With CLS Rate Adaption (Protos CLS), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	biV Pacing With Accelerometer Based Rate Adaption (Stratos LV), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	t-test, 2 sided
	Comments

12. Secondary Outcome

Title	Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Systolic Volume
Time Frame	Change from baseline to six months post-procedure

Outcome Measure Data

Analysis Population Description

Subjects with paired baseline and 6-month echocardiography data.

Arm/Group Title	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)
Arm/Group Description	Biventricular pacing group with Closed Loop Stimulation rate adaptation (Protos CLS device)	Biventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device)
Measure Participants	36	42	15
Mean (Standard Error) [mL]	-7.7 (1.7)	-5.9 (2.1)	8.7 (4.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	biV-pacing With CLS Rate Adaption (Protos CLS), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	biV Pacing With Accelerometer Based Rate Adaption (Stratos LV), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments

13. Secondary Outcome

Title	Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Diastolic Volume
Time Frame	Change from baseline to six months post-procedure

Outcome Measure Data

Analysis Population Description

Subjects with paired baseline and 6-month echocardiography data.

Arm/Group Title	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)
Arm/Group Description	Biventricular pacing group with Closed Loop Stimulation rate adaptation (Protos CLS device)	Biventricular pacing group with accelerometer based rate adaption (Stratos LV device)	Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device)
Measure Participants	36	42	15
Mean (Standard Error) [mL]	-10.1 (3.5)	-7.1 (4.0)	9.5 (8.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	biV-pacing With CLS Rate Adaption (Protos CLS), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.039
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	biV Pacing With Accelerometer Based Rate Adaption (Stratos LV), RV Pacing With Accelerometer Based Rate Adaption (Stratos LV)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.047
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Study duration with a mean enrollment duration of 19.6 months.
Adverse Event Reporting Description	Adverse events are included for all study groups together.
Arm/Group Title	All Groups
Arm/Group Description
All Cause Mortality
	All Groups
	Affected / at Risk (%)	# Events
Total	10/153 (6.5%)
Serious Adverse Events
	All Groups
	Affected / at Risk (%)	# Events
Total	58/153 (37.9%)
Cardiac disorders
Device related	4/153 (2.6%)	5
LV lead related	10/153 (6.5%)	10
Other medical	45/153 (29.4%)	65
Procedure	4/153 (2.6%)	4
RV-lead related	9/153 (5.9%)	11
Other (Not Including Serious) Adverse Events
	All Groups
	Affected / at Risk (%)	# Events
Total	102/153 (66.7%)
Cardiac disorders
LV lead related	30/153 (19.6%)	30
RV lead related	2/153 (1.3%)	2
Device related	12/153 (7.8%)	12
Procedure	48/153 (31.4%)	53
Other medical	55/153 (35.9%)	90

Limitations/Caveats

Early termination due lack of enrollment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results.