Interventricular Delay of Lumax HF-T for Heart Failure

• Sponsor: Biotronik, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00508391
• Collaborator: (none)
• Enrollment: 122
• Locations: 19
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate that the safety and efficacy of the Lumax HF-T with optimized interventricular delay biventricular pacing (OPT) is non-inferior to the Lumax HF-T with simultaneous biventricular pacing (SIM) in patients with heart failure requiring cardiac resynchronization therapy.

Condition or Disease	Intervention/Treatment	Phase
Congestive Heart Failure	Device: Optimized interventricular delay biventricular pacing	Phase 2

Detailed Description

This study is a randomized, double-blinded, crossover, multi-center, prospective trial. The study will consist of up to 122 subjects who require treatment of advanced heart failure through cardiac resynchronization therapy (CRT) with back-up defibrillation capabilities. Eligible patients will have a successfully implanted BIOTRONIK Lumax HF-T CRT-D system and have received simultaneous biventricular pacing for a minimum of 90 days prior to enrollment. The 90-day period is being required to allow the treatment effect of CRT therapy with SIM to be complete and to ensure the patient is receiving a stable and optimal CHF medical regimen. The patients will have the interventricular delay feature programmed after a standardized optimization procedure. Patients, along with study personnel evaluating the study endpoint measures, will be blinded to the type of CRT therapy delivered during the study follow-up period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Clinical Investigation to Study Safety and Efficacy of the Interventricular Delay Feature of the Lumax HF-T Device for Heart Failure.
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Simultaneous 1st, Optimized 2nd Lumax HF-T device programmed to simultaneous biventricular pacing first for 30 days, followed by optimized biventricular pacing for 30 days.	Device: Optimized interventricular delay biventricular pacing; Lumax HF-T with optimized interventricular delay biventricular pacing; Other Names: Optimized CRT, Interventricular delay
Experimental: Optimized 1st, Simultaneous 2nd Lumax HF-T device programmed to optimized biventricular pacing first for 30 days, followed by simultaneous biventricular pacing for 30 days.	Device: Optimized interventricular delay biventricular pacing; Lumax HF-T with optimized interventricular delay biventricular pacing; Other Names: Optimized CRT, Interventricular delay

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Classified as "Not Worsened" for Changes in the Minnesota Living With Heart Failure Questionnaire and Six-minute Walk Distance Between Periods of Optimized and Simultaneous Biventricular Pacing [60 days after enrollment]

   The purpose is to evaluate the effectiveness of optimized pacing (OPT) compared to simultaneous pacing (SIM). The hypothesis is evaluated based on a responder classification. Subjects are classified "not worsened" if after 30 days of OPT the quality of life (QOL) score is no more than 10 points higher and the six-minute walk distance is no more than 35 meters lower than after 30 days of SIM. The Minnesota Living with Heart Failure questionnaire, a 21 question patient-completed survey, was used for QOL. Each question had a possible score of 0 (best) to 5 (worst), for a total of 0 to 105.

2. Percent of Subjects That Did Not Experience an Adverse Event That Require Additional Invasive Intervention to Resolve, Specifically Related to the Interventricular Delay Feature of the Lumax HF-T Heart Failure Device [60 days after enrollment]

   The purpose of primary endpoint two is to evaluate adverse events that require additional invasive intervention to resolve, specifically those events that are directly related to the interventricular delay feature of the Lumax HF-T heart failure device. These adverse events include any software issues related to the programming of the interventricular delay or any event that occurs after optimization of the interventricular delay and that can be directly attributed to the use of the feature.

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

• Successfully implanted with a BIOTRONIK Lumax HF-T CRT-D system and have received SIM for a minimum of 30 days prior to enrollment. A successful implantation is defined as having a measured LV pacing threshold which allows for a minimum 1-volt safety margin without any phrenic nerve stimulation at the time of enrollment.

• Treated with stable and optimal CHF medications, which includes an ACE inhibitor (ACE-I) or Angiotensin Receptor Blocker (ARB) at therapeutic dose for 1 month prior to enrollment, if tolerated, and a Beta Blocker that is approved and indicated for HF for 3 months prior to enrollment, if tolerated, with a stable dosage for 1 month prior to enrollment. If the patient is intolerant of ACE-I or beta blockers, documented evidence must be available. Eplerenone requires dosage stability for 1 month prior to enrollment. Diuretics may be used as necessary to keep the patient euvolemic. Therapeutic equivalence for ACE-I substitutions is allowed within the enrollment stability timeliness. Stable is defined as no more than a 100% increase or a 50% decrease in dose.

• Age ≥ 18 years

• Able to understand the nature of the study and give informed consent

• Able to complete all testing required by the clinical protocol, including the 6-minute walk test and QOL questionnaire

• 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 6 months

• Expected to receive heart transplantation within 6 months

• Have had more than 1 CHF-related hospitalization within past 30 days

• Currently receiving IV inotropic medications

• Chronic atrial fibrillation

• Enrolled in another cardiovascular or pharmacological clinical investigation, except for FDA required post-market registries

• Any condition preventing the patient from being able to perform required testing

• Presence of another life-threatening, underlying illness separate from their cardiac disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Solano Cardiology	Fairfield	California	United States	94533
2	Cardiac Arrhythmia Associates	La Jolla	California	United States	92307
3	Sansum Clinic	Santa Barbara	California	United States	93110
4	Cardiology Associates Medical Group	Ventura	California	United States	93003
5	Cardiac Disease Specialists, P.C.	Atlanta	Georgia	United States	30309
6	Georgia Arrhythmia Consultants	Macon	Georgia	United States	31201
7	Fananapazir	Cumberland	Maryland	United States	21502
8	St. Elizabeth's Medical Center	Boston	Massachusetts	United States	02135
9	Michigan Cardiovascular Institute	Saginaw	Michigan	United States	48601
10	SSM Medical Group	St. Louis	Missouri	United States	63117
11	Gateway Cardiology	St. Louis	Missouri	United States	63128
12	Salem Cardiology	Salem	Oregon	United States	97302
13	Palmetto Cardiology	Columbia	South Carolina	United States	29204
14	Pee Dee Cardiology	Florence	South Carolina	United States	29505
15	Cardiology Consultants	Spartanburg	South Carolina	United States	29303
16	Lone Star Heart Center	Amarillo	Texas	United States	79106
17	Cardiac Associates of Dallas	Dallas	Texas	United States	75230
18	Yakima Heart Center	Yakima	Washington	United States	98902
19	University Hospital Zurich	Zurich		Switzerland

Sponsors and Collaborators

• Biotronik, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00508391
• Other Study ID Numbers: G070019
• First Posted: Jul 30, 2007
• Last Update Posted: Jan 26, 2010
• Last Verified: Jan 1, 2010

• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from each investigator's general patient population at the medical clinic and selected according to the study inclusion/exclusion criteria.
Pre-assignment Detail	All subjects enrolled in the study were previously implanted with a Lumax HF-T heart failure device. The study utilized an intention-to-treat analysis where subjects were analyzed according to the randomized treatment order, regardless of whether they received the treatment in the order stipulated by the protocol.

Arm/Group Title	Simultaneous 1st, Optimized 2nd	Optimized 1st, Simultaneous 2nd
Arm/Group Description	Lumax HF-T device programmed to simultaneous biventricular pacing first for 30 days, followed by optimized biventricular pacing for 30 days.	Lumax HF-T device programmed to optimized biventricular pacing first for 30 days, followed by simultaneous biventricular pacing for 30 days.
Period Title: First Treatment
STARTED	60	62
COMPLETED	54	59
NOT COMPLETED	6	3
Period Title: First Treatment
STARTED	54	59
COMPLETED	52	59
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Simultaneous 1st, Optimized 2nd	Optimized 1st, Simultaneous 2nd	Total
Arm/Group Description	Lumax HF-T device programmed to simultaneous biventricular pacing first for 30 days, followed by optimized biventricular pacing for 30 days.	Lumax HF-T device programmed to optimized biventricular pacing first for 30 days, followed by simultaneous biventricular pacing for 30 days.	Total of all reporting groups
Overall Participants	60	62	122
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 35%	27 43.5%	48 39.3%
>=65 years	39 65%	35 56.5%	74 60.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.2 (14.1)	66.1 (12.0)	67.1 (13.1)
Sex: Female, Male (Count of Participants)
Female	16 26.7%	10 16.1%	26 21.3%
Male	44 73.3%	52 83.9%	96 78.7%
Region of Enrollment (participants) [Number]
United States	58 96.7%	59 95.2%	117 95.9%
Switzerland	2 3.3%	3 4.8%	5 4.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Classified as "Not Worsened" for Changes in the Minnesota Living With Heart Failure Questionnaire and Six-minute Walk Distance Between Periods of Optimized and Simultaneous Biventricular Pacing
Description	The purpose is to evaluate the effectiveness of optimized pacing (OPT) compared to simultaneous pacing (SIM). The hypothesis is evaluated based on a responder classification. Subjects are classified "not worsened" if after 30 days of OPT the quality of life (QOL) score is no more than 10 points higher and the six-minute walk distance is no more than 35 meters lower than after 30 days of SIM. The Minnesota Living with Heart Failure questionnaire, a 21 question patient-completed survey, was used for QOL. Each question had a possible score of 0 (best) to 5 (worst), for a total of 0 to 105.
Time Frame	60 days after enrollment

Outcome Measure Data

Analysis Population Description

Study utilized an intention-to-treat analysis. 111 out of 122 enrolled subjects completed the primary endpoint follow-up. 106 of these subjects met analysis criteria based on paired quality of life and six-minute walk data at the one and two month visits. Subjects not included in analysis either withdrew consent or had incomplete study measures.

Arm/Group Title	Simultaneous 1st, Optimized 2nd	Optimized 1st, Simultaneous 2nd	Total Subjects
Arm/Group Description	Lumax HF-T device programmed to simultaneous biventricular pacing first for 30 days, followed by optimized biventricular pacing for 30 days.	Lumax HF-T device programmed to optimized biventricular pacing first for 30 days, followed by simultaneous biventricular pacing for 30 days.	Total subjects enrolled in study.
Measure Participants	51	55	106
Number [Percent of Subjects]	65	62	63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Total Subjects
	Comments	Efficacy was assessed in a non-inferiority, responder classification design where the proportion of total subjects classified as "not worsened" after changing from optimized to simultaneous biventricular pacing was compared to an objective performance criteria. An effect of gender analysis was performed on the primary efficacy endpoint to compare the proportion of males and females classified as "not worsened" after changing from optimized to simultaneous biventricular pacing.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The non-inferiority hypothesis utilized an objective performance criteria of 63% with a clinically significant difference of 12%. For the non-inferiority hypothesis, the one-sided Type I error was set to 0.05 and the statistical power was set to 80%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Objective Performance Criteria
	Estimated Value	63
	Confidence Interval	(1-Sided) 95%; 54.8 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percent of Subjects That Did Not Experience an Adverse Event That Require Additional Invasive Intervention to Resolve, Specifically Related to the Interventricular Delay Feature of the Lumax HF-T Heart Failure Device
Description	The purpose of primary endpoint two is to evaluate adverse events that require additional invasive intervention to resolve, specifically those events that are directly related to the interventricular delay feature of the Lumax HF-T heart failure device. These adverse events include any software issues related to the programming of the interventricular delay or any event that occurs after optimization of the interventricular delay and that can be directly attributed to the use of the feature.
Time Frame	60 days after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Simultaneous 1st, Optimized 2nd	Optimized 1st, Simultaneous 2nd	Total Subjects
Arm/Group Description	Lumax HF-T device programmed to simultaneous biventricular pacing first for 30 days, followed by optimized biventricular pacing for 30 days.	Lumax HF-T device programmed to optimized biventricular pacing first for 30 days, followed by simultaneous biventricular pacing for 30 days.	Total subjects enrolled in study.
Measure Participants	60	62	122
Number [Percent of Subjects]	100	100	100

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Total Subjects
	Comments	Safety will be evaluated in a non-inferiority format. The null hypothesis is the percent of subjects that did not experience an adverse event with an active interventricular delay feature at two months is inferior to 90% with a clinically significant difference of 10%
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The non-inferiority hypothesis has a one-sided Type I error of 0.05 with an 80% statistical power.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Objective Performance Criteria
	Estimated Value	100
	Confidence Interval	(1-Sided) 95%; 97.6 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event data was collected at each study visit until the final study visit at 6 months post enrollment.
Arm/Group Title	Simultaneous 1st, Optimized 2nd		Optimized 1st, Simultaneous 2nd		Total Subjects
Arm/Group Description	Lumax HF-T device programmed to simultaneous biventricular pacing first for 30 days, followed by optimized biventricular pacing for 30 days.		Lumax HF-T device programmed to optimized biventricular pacing first for 30 days, followed by simultaneous biventricular pacing for 30 days.		Total subjects enrolled in study.
All Cause Mortality
	Simultaneous 1st, Optimized 2nd		Optimized 1st, Simultaneous 2nd		Total Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Simultaneous 1st, Optimized 2nd		Optimized 1st, Simultaneous 2nd		Total Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/60 (5%)		5/62 (8.1%)		8/122 (6.6%)
Cardiac disorders
Atrial arrhythmia requring invasive intervention to resolve	1/60 (1.7%)	1	1/62 (1.6%)	1	2/122 (1.6%)	2
Ventricular arrhythmia requiring invasive intervention to resolve	0/60 (0%)	0	2/62 (3.2%)	2	2/122 (1.6%)	2
Non-heart failure cardiac symptoms requiring invasive intervention to resolve	1/60 (1.7%)	1	1/62 (1.6%)	1	2/122 (1.6%)	2
Other cardiac condition requiring invasive intervention to resolve	1/60 (1.7%)	1	3/62 (4.8%)	4	4/122 (3.3%)	5
Other (Not Including Serious) Adverse Events
	Simultaneous 1st, Optimized 2nd		Optimized 1st, Simultaneous 2nd		Total Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/60 (11.7%)		14/62 (22.6%)		21/122 (17.2%)
Cardiac disorders
Worsening heart failure	4/60 (6.7%)	4	8/62 (12.9%)	9	12/122 (9.8%)	13
Other cardiac symptom	3/60 (5%)	3	7/62 (11.3%)	8	10/122 (8.2%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.