Heart Failure
Conditions
Brief summary
The objective of this MultiPole Pacing (MPP) sub-study of the QP ExCELs study is to demonstrate that the MPP feature is effective by converting a percentage of cardiac resynchronization therapy (CRT) non-responders to responders. The MPP sub-study is a single-arm, multi-center, prospective trial within the ongoing QP ExCELs study (NCT02290028).
Interventions
DEVICEMultiPole Pacing
CRT non-responders are programmed with MultiPole pacing ON.
Sponsors
Biotronik, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Currently enrolled in the ongoing QP ExCELs study * Successfully implanted with a BIOTRONIK Ilivia 7 HF-T QP family CRT-D system, or future-marketed CRT-D system with the MPP feature. Successful implantation is defined as having at least two LV pacing vectors with a measured pacing threshold of ≤ 5.0 V @ any pulse width (allowing for a minimum 2.5 V safety margin) without phrenic nerve stimulation at the final programmed pacing output at the time of enrollment into the MPP sub-study. * CRT Responder Assessment classification as Worsened or Unchanged * Standard continuous biventricular (BiV) pacing from implant until the 6-Month QP ExCELs follow-up visit. (Implant to 3-Month QP ExCELs follow-up who qualify due to a Heart Failure (HF) hospitalization event) * Able to understand the nature of the sub-study and give informed consent * Available for an additional follow-up visit specific to the MPP sub-study at the investigational site * No evidence of non-compliance to their ongoing commitment in the QP ExCELs study
Exclusion criteria
* Have a life expectancy of less than 6 months * Expected to receive heart transplantation or ventricular assist device within 6 months * Chronic atrial fibrillation * Presence of another life-threatening, underlying illness separate from their cardiac disorder * Received MPP pacing prior to enrolment into the MPP sub-study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac Resynchronization Therapy (CRT) Responder Status With the MPP Feature | Enrollment to 6 Months | Count of participants who are classified as Improved, where responder classification is derived from a clinical composite score (CCS) based on changes in New York Heart Association (NYHA) class, Heart Failure (HF) hospitalization, and cardiovascular death. Responder classification at 6 months (evaluated compared to MPP Enrollment Visit) : * Improved * No HF hospitalization or cardiovascular death, AND * NYHA class is improved * Unchanged * No HF hospitalization or cardiovascular death, AND * NYHA class is unchanged * Worsened * HF hospitalization or cardiovascular death has occurred, OR * NYHA class is worsened |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Without MPP System Related Adverse Events Requiring Additional Invasive Intervention to Resolve at 6 Months. | Enrollment to 6 Months | Evaluate adverse events that require additional invasive intervention to resolve specifically related to the MPP feature. These adverse events include any software issues related to MPP programming or any adverse event that occurs while MPP is enabled and that may be attributed to the use of the MPP feature. Outcome was evaluated as an adverse event free-rate (AEFR). |
| Clinical Composite Score (CCS) + Patient Global Assessment (PGA) Responder Status Utilizing a Modified CCS That Incorporates the PGA | Enrollment to 6 Months | Evaluate a modified CCS, determining a responder classification based on changes in NYHA class, PGA, HF hospitalization, and cardiovascular death, where the PGA will ask participantss to assess how their overall status has changed since prior to receiving CRT therapy (markedly better, better, unchanged, worse, markedly worse). Modified responder classification (CCS + PGA) at 6 months (evaluated compared to MPP Enrollment Visit): * Improved * No HF hospitalization or cardiovascular death, AND * Neither NYHA class is worsened or PGA is worsened (worse or markedly worse), AND * NYHA class is improved or PGA is improved (better or markedly better) * Unchanged * No HF hospitalization or cardiovascular death, AND * NYHA class is unchanged, AND * PGA is unchanged (unchanged) * Worsened * HF hospitalization or cardiovascular death has occurred, OR * NYHA class is worsened or PGA is worsened (worse or markedly worse) |
| CCS Responder Status Utilizing an Expanded Responder Classification | Enrollment to 6 Months | Evaluate a modified CCS with an expanded responder classification where Improved and Unchanged are considered responders. Responder classification at 6 months (evaluated compared to MPP Enrollment Visit) : * Improved * No HF hospitalization or cardiovascular death, AND * NYHA class is improved * Unchanged * No HF hospitalization or cardiovascular death, AND * NYHA class is unchanged * Worsened * HF hospitalization or cardiovascular death has occurred, OR * NYHA class is worsened |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MultiPole Pacing Traditional biventricular pacing CRT non-responders at the 3 or 6 month QP ExCELs study follow-up.
MultiPole Pacing: CRT non-responders are programmed with MultiPole pacing ON. | 53 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Study closure | 7 |
Baseline characteristics
| Characteristic | MultiPole Pacing | — |
|---|---|---|
| Age, Continuous | 69.3 Years STANDARD_DEVIATION 12.13 | — |
| Height | 68.5 in STANDARD_DEVIATION 4 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 11 Participants | — |
| Sex: Female, Male Male | 42 Participants | — |
| Weight | 212.7 Pounds STANDARD_DEVIATION 52.69 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 53 |
| other Total, other adverse events | 6 / 53 |
| serious Total, serious adverse events | 5 / 53 |
Outcome results
Primary
Cardiac Resynchronization Therapy (CRT) Responder Status With the MPP Feature
Count of participants who are classified as Improved, where responder classification is derived from a clinical composite score (CCS) based on changes in New York Heart Association (NYHA) class, Heart Failure (HF) hospitalization, and cardiovascular death. Responder classification at 6 months (evaluated compared to MPP Enrollment Visit) : * Improved * No HF hospitalization or cardiovascular death, AND * NYHA class is improved * Unchanged * No HF hospitalization or cardiovascular death, AND * NYHA class is unchanged * Worsened * HF hospitalization or cardiovascular death has occurred, OR * NYHA class is worsened
Time frame: Enrollment to 6 Months
Population: Participants who have completed the MultiPole Pacing (MPP) Sub-study 6-Month follow-up visit or experienced a qualifying outcome event as of January 23, 2020.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MultiPole Pacing | Cardiac Resynchronization Therapy (CRT) Responder Status With the MPP Feature | Improved | 16 Participants |
| MultiPole Pacing | Cardiac Resynchronization Therapy (CRT) Responder Status With the MPP Feature | Unchanged | 23 Participants |
| MultiPole Pacing | Cardiac Resynchronization Therapy (CRT) Responder Status With the MPP Feature | Worsened | 6 Participants |
Comparison: The primary endpoint 1 hypothesis was evaluated by performing an exact, binomial test comparing the binomial proportion of 'improved' patients to 3.0% with power of 80% and type 1 error (alpha) of 0.0224. A pre-planned interim analysis at 45 patients required a type 1 error (alpha) of 0.0026 to demonstrate significance.p-value: <0.0001Exact, binomial, one-sided
Secondary
CCS Responder Status Utilizing an Expanded Responder Classification
Evaluate a modified CCS with an expanded responder classification where Improved and Unchanged are considered responders. Responder classification at 6 months (evaluated compared to MPP Enrollment Visit) : * Improved * No HF hospitalization or cardiovascular death, AND * NYHA class is improved * Unchanged * No HF hospitalization or cardiovascular death, AND * NYHA class is unchanged * Worsened * HF hospitalization or cardiovascular death has occurred, OR * NYHA class is worsened
Time frame: Enrollment to 6 Months
Population: Participants who have completed the MPP Sub-Study 6-Month follow-up visit or experienced a qualifying outcome event as of January 23, 2020.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MultiPole Pacing | CCS Responder Status Utilizing an Expanded Responder Classification | Responder | 39 Participants |
| MultiPole Pacing | CCS Responder Status Utilizing an Expanded Responder Classification | Non-Responder | 6 Participants |
Secondary
Clinical Composite Score (CCS) + Patient Global Assessment (PGA) Responder Status Utilizing a Modified CCS That Incorporates the PGA
Evaluate a modified CCS, determining a responder classification based on changes in NYHA class, PGA, HF hospitalization, and cardiovascular death, where the PGA will ask participantss to assess how their overall status has changed since prior to receiving CRT therapy (markedly better, better, unchanged, worse, markedly worse). Modified responder classification (CCS + PGA) at 6 months (evaluated compared to MPP Enrollment Visit): * Improved * No HF hospitalization or cardiovascular death, AND * Neither NYHA class is worsened or PGA is worsened (worse or markedly worse), AND * NYHA class is improved or PGA is improved (better or markedly better) * Unchanged * No HF hospitalization or cardiovascular death, AND * NYHA class is unchanged, AND * PGA is unchanged (unchanged) * Worsened * HF hospitalization or cardiovascular death has occurred, OR * NYHA class is worsened or PGA is worsened (worse or markedly worse)
Time frame: Enrollment to 6 Months
Population: Participants who have completed the MPP Sub-Study 6-Month follow-up visit or experienced a qualifying outcome event as of January 23, 2020.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MultiPole Pacing | Clinical Composite Score (CCS) + Patient Global Assessment (PGA) Responder Status Utilizing a Modified CCS That Incorporates the PGA | Improved | 27 Participants |
| MultiPole Pacing | Clinical Composite Score (CCS) + Patient Global Assessment (PGA) Responder Status Utilizing a Modified CCS That Incorporates the PGA | Unchanged | 11 Participants |
| MultiPole Pacing | Clinical Composite Score (CCS) + Patient Global Assessment (PGA) Responder Status Utilizing a Modified CCS That Incorporates the PGA | Worsened | 7 Participants |
Secondary
Percentage of Participants Without MPP System Related Adverse Events Requiring Additional Invasive Intervention to Resolve at 6 Months.
Evaluate adverse events that require additional invasive intervention to resolve specifically related to the MPP feature. These adverse events include any software issues related to MPP programming or any adverse event that occurs while MPP is enabled and that may be attributed to the use of the MPP feature. Outcome was evaluated as an adverse event free-rate (AEFR).
Time frame: Enrollment to 6 Months
Population: Evaluable participants for Secondary Endpoint 1 include all participants who have been enrolled into the MPP Sub-Study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MultiPole Pacing | Percentage of Participants Without MPP System Related Adverse Events Requiring Additional Invasive Intervention to Resolve at 6 Months. | 100 percentage of participants |