Congestive Heart Failure
Conditions
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.
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.
Interventions
DEVICEOptimized interventricular delay biventricular pacing
Lumax HF-T with optimized interventricular delay biventricular pacing
Sponsors
Biotronik, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Switzerland, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 60 |
| 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. | 62 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Treatment | Withdrawal by Subject | 6 | 3 |
| Second Treatment | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Simultaneous 1st, Optimized 2nd | Optimized 1st, Simultaneous 2nd | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 39 Participants | 35 Participants | 74 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 27 Participants | 48 Participants |
| Age Continuous | 68.2 years STANDARD_DEVIATION 14.1 | 66.1 years STANDARD_DEVIATION 12 | 67.1 years STANDARD_DEVIATION 13.1 |
| Region of Enrollment Switzerland | 2 participants | 3 participants | 5 participants |
| Region of Enrollment United States | 58 participants | 59 participants | 117 participants |
| Sex: Female, Male Female | 16 Participants | 10 Participants | 26 Participants |
| Sex: Female, Male Male | 44 Participants | 52 Participants | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 60 | 14 / 62 | 21 / 122 |
| serious Total, serious adverse events | 3 / 60 | 5 / 62 | 8 / 122 |
Outcome results
Primary
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
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Simultaneous 1st, Optimized 2nd | 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 | 65 Percent of Subjects |
| Optimized 1st, Simultaneous 2nd | 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 | 62 Percent of Subjects |
| Total Subjects | 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 | 63 Percent of Subjects |
Comparison: 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.Non-inferiority comparison
Primary
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
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simultaneous 1st, Optimized 2nd | 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 | 100 Percent of Subjects |
| Optimized 1st, Simultaneous 2nd | 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 | 100 Percent of Subjects |
| Total Subjects | 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 | 100 Percent of Subjects |
Comparison: 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%Non-inferiority comparison