Heart Failure
Conditions
Keywords
CRT-D therapy, quadripolar left ventricular lead
Brief summary
The QP ExCELs study is designed to confirm safety and efficacy of the BIOTRONIK Sentus OTW QP left ventricular leads to satisfy FDA requirements for regulatory approval of the leads in the US. The Sentus OTW QP leads received FDA approval on May 4, 2017. Long-term safety of the BIOTRONIK Sentus OTW QP left ventricular leads will be confirmed during the ongoing post approval phase (US sites only). A protocol update was implemented on September 6, 2019 to transition the long-term follow up for the ongoing Sentus QP Study to a new EP PASSION real-world data methodology.
Interventions
DEVICESentus QP left ventricular lead
Implantation of quadripolar left ventricular lead in patients with CRT-D indication
Sponsors
Biotronik, Inc.
Biotronik SE & Co. KG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Standard CRT-D indication according to clinical routine * De novo implantation or upgrade from existing ICD or pacemaker implant utilizing a BIOTRONIK CRT-D system with IS4 LV port and Sentus QP LV lead * Patient is able to understand the nature of the clinical investigation and provide written informed consent * Patient is able and willing to complete all routine study visits at the investigational site through 5 years of follow-up * Patient accepts Home Monitoring® concept * Age ≥ 18 years
Exclusion criteria
* Chronic atrial fibrillation * Contraindication to CRT-D therapy * Currently implanted with an endocardial or epicardial left ventricular lead or had prior attempt to place a left ventricular lead * Cardiac surgical procedure, such as coronary artery bypass graft or valve surgery that is planned to occur within 6 months after implant or ablation that is planned to occur within 90 days after implant (ablations planned to occur prior to or at implant are not exclusionary) * Expected to receive a heart transplant or ventricular assist device within 6 months * Life expectancy less than 12 months * Participation in any other investigational cardiac clinical investigation during the course of the study * Presence of another life-threatening, underlying illness separate from their cardiac disorder * Pregnant or breast-feeding at time of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sentus QP Related Complication-free Rate Through 6 Months | 6 months | The purpose of primary endpoint 1 is to evaluate the Sentus QP related complication-free rate through 6 months post-implant. This is evaluated as a percentage of participants without a complication. |
| Percentage of Participants With Acceptable Pacing Threshold of Sentus QP Lead in Permanently Programmed Vector at 3 Months | 3 months | The purpose of primary endpoint 2 is to evaluate the LV lead pacing threshold for the permanently programmed pacing vector at 3 months post-implant.This was evaluated by performing an exact, binomial test comparing the percentage of participants with acceptable pacing thresholds to a performance goal of 88%. LV threshold values of less than or equal to 2.5 V at 0.4 ms in the permanently programmed vector are considered acceptable. |
| Sentus QP Related Complication-free Rate | Up to 4 years | The purpose of primary endpoint 3 is to evaluate the Sentus QP related complication-free rate through study termination (post approval phase). This is evaluated as a percentage of participants without a complication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sentus QP Acceptable R-wave Sensed Amplitude at 3 Months Per Lead Model | 3 months | The purpose of this secondary endpoint is to evaluate acceptable LV lead sensing amplitude at 3 months post-implantation. This was evaluated as the number of participants with an acceptable LV sensing amplitude out of the total number of participants. R-wave sensed mean amplitude of greater than or equal to 2 mV is considered acceptable. |
| Sentus QP Acceptable Pacing Impedance at 3 Months Per Lead Model | 3 months | The purpose of this secondary endpoint is to evaluate the acceptable LV lead pacing impedance at 3 months post-implantation. This was evaluated as the number of participants with an acceptable LV pacing impedance out of the total participants. LV impedance values of greater than 200 Ohms and less than 2000 Ohms is considered acceptable. |
| Sentus QP Related Complication-free Rate Per Lead Model | Up to 4 years | The purpose of secondary endpoint 7 is to evaluate the Sentus QP related complication-free rate through study termination (post approval phase). This is evaluated as percentage of participants without a complication per lead model. |
| Individual Sentus QP Adverse Event Rates | Up to 4 years | The purpose of secondary endpoint 8 is to evaluate the rate of individual types of adverse events related to the Sentus QP lead through study termination (post approval phase). This is evaluated as the percentage of participants with a specific adverse event out of the total participants. |
| Number of Participants Successfully Reprogrammed to Resolve Phrenic Nerve Stimulation or High Pacing Threshold | 12 months | The purpose of this secondary endpoint is to evaluate the number of participants in whom phrenic nerve stimulation or high LV pacing threshold was be successfully resolved by reprogramming of the LV pacing vector. This is evaluated as the number of participants with successful reprogramming out of all participants experiencing phrenic nerve stimulation or high LV pacing threshold. LV pacing threshold resulting in invasive intervention, or, in the absence of intervention, a lead threshold that has increased two fold from the chronic threshold value, and is unable to achieve a 2:1 safety margin at follow-up is considered a high LV pacing threshold. |
| Sentus QP Time to Complication | 6 months | The purpose of this secondary is to evaluate the Sentus related complication-free rate through 6 months post-implant by the Kaplan-Meier method. The below table shows Kaplan-Meier estimates of the estimated freedom from Sentus related complications at 180 days. |
| Sentus QP Acceptable Pacing Threshold in Permanently Programmed Vector at 3 Months Per Lead Model | 3 months | The purpose of the secondary endpoint is to evaluate the LV lead pacing threshold for the permanently programmed pacing vector at 3 months post-implantation in the two different lead types, Sentus OTW QP L and Sentus OTW QP S. This was evaluated as the number of participants with an acceptable pacing threshold out of the total number of patients for each lead model. LV threshold values of less than or equal to 2.5 V at 0.4 ms in the permanently programmed vector is considered acceptable. |
| Sentus QP Acceptable Pacing Threshold in Novel Vectors at 3 Months | 3 months | The purpose of this secondary endpoint is to evaluate the number of participants with at least one acceptable LV lead pacing threshold in a novel pacing vector at 3 months post-implantation. This was evaluated as the number of participants with at least one acceptable LV pacing threshold in a novel pacing vector out of the total number of participants with completed novel pacing threshold testing. LV threshold values of less than or equal to 2.5 V at 0.4 ms in a novel pacing vector is considered acceptable. |
Countries
Australia, Austria, Denmark, Germany, Hungary, Israel, Italy, Slovakia, Spain, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sentus QP Left Ventricular Lead Participants consented and implanted with a Sentus QP left ventricular lead and CRT-D. | 2,222 |
| Total | 2,222 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 217 |
| Overall Study | Lost to Follow-up | 34 |
| Overall Study | Miscellaneous | 10 |
| Overall Study | No longer under care of study physician | 76 |
| Overall Study | Planned study completion at 12 months | 257 |
| Overall Study | Sentus lead or required CRT-D explanted | 55 |
| Overall Study | Sentus lead or required CRT-D was not implanted | 186 |
| Overall Study | Study site closure | 44 |
| Overall Study | Transition to EP PASSION | 1,295 |
| Overall Study | Withdrawal by Subject | 52 |
Baseline characteristics
| Characteristic | Sentus QP Left Ventricular Lead | — |
|---|---|---|
| Age, Continuous | 68.8 Years STANDARD_DEVIATION 10.8 | — |
| Height | 68.0 Inches STANDARD_DEVIATION 4 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 683 Participants | — |
| Sex: Female, Male Male | 1539 Participants | — |
| Weight | 197.3 Pounds STANDARD_DEVIATION 50 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 217 / 2,226 |
| other Total, other adverse events | 711 / 2,226 |
| serious Total, serious adverse events | 290 / 2,226 |
Outcome results
Primary
Percentage of Participants With Acceptable Pacing Threshold of Sentus QP Lead in Permanently Programmed Vector at 3 Months
The purpose of primary endpoint 2 is to evaluate the LV lead pacing threshold for the permanently programmed pacing vector at 3 months post-implant.This was evaluated by performing an exact, binomial test comparing the percentage of participants with acceptable pacing thresholds to a performance goal of 88%. LV threshold values of less than or equal to 2.5 V at 0.4 ms in the permanently programmed vector are considered acceptable.
Time frame: 3 months
Population: All participants in the Pre-Market cohort, defined as the study participants who were consented and implanted with a Sentus QP LV lead on or before January 29, 2016, and with completed threshold testing at 3 months post-implant or with available data from remote monitoring or next visits (as pre-specified in the protocol).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sentus QP Left Ventricular Lead | Percentage of Participants With Acceptable Pacing Threshold of Sentus QP Lead in Permanently Programmed Vector at 3 Months | 93.4 percentage of participants |
Comparison: Primary endpoint 2 was evaluated by performing an exact, binomial test comparing an observed proportion (rate of acceptable LV pacing thresholds at the permanently programmed pacing vector at 3 months) to 88%, with Type I error (alpha) of 0.025 and power of 80%. The lower, two-sided 95% confidence bound for the percentage of subjects with an acceptable LV pacing threshold in the permanently programmed pacing vector must be greater than 88.0%.p-value: =0.002Exact, binomial
Primary
Sentus QP Related Complication-free Rate
The purpose of primary endpoint 3 is to evaluate the Sentus QP related complication-free rate through study termination (post approval phase). This is evaluated as a percentage of participants without a complication.
Time frame: Up to 4 years
Population: All participants in the Post-Market cohort, which included all participants who were enrolled with planned 5 year follow-up and were successfully implanted with a Sentus QP left ventricular lead.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sentus QP Left Ventricular Lead | Sentus QP Related Complication-free Rate | 98.03 percentage of participants |
Comparison: Primary endpoint 3 will be evaluated by performing an exact, binomial test comparing the observed proportion (overall complication-free rate at 5 years) to the performance goal of 92.5%, with Type I error (alpha) of 0.025 and power of 80%. The lower, two-sided 95% confidence bound for the overall complication-free rate must be greater than 92.5%
Primary
Sentus QP Related Complication-free Rate Through 6 Months
The purpose of primary endpoint 1 is to evaluate the Sentus QP related complication-free rate through 6 months post-implant. This is evaluated as a percentage of participants without a complication.
Time frame: 6 months
Population: All participants in the Pre-Market cohort, defined as the study participants who were consented and implanted with a Sentus QP LV lead on or before January 29, 2016.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sentus QP Left Ventricular Lead | Sentus QP Related Complication-free Rate Through 6 Months | 97.1 percentage of participants |
Comparison: Primary endpoint 1 was evaluated by performing an exact, binomial test comparing the observed proportion (overall complication-free rate at 6 months) to the performance goal of 90.0%, with Type I error (alpha) of 0.025 and power of 80%. The lower, two-sided 95% confidence bound for the overall complication-free rate must be greater than 90.0%.p-value: <0.0001Exact, binomial
Secondary
Individual Sentus QP Adverse Event Rates
The purpose of secondary endpoint 8 is to evaluate the rate of individual types of adverse events related to the Sentus QP lead through study termination (post approval phase). This is evaluated as the percentage of participants with a specific adverse event out of the total participants.
Time frame: Up to 4 years
Population: All participants in the Post-Market cohort, which included all participants who were enrolled with planned 5 year follow-up and were successfully implanted with a Sentus QP left ventricular lead.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sentus QP Left Ventricular Lead | Individual Sentus QP Adverse Event Rates | Dislodgements | 1.39 percentage of participants |
| Sentus QP Left Ventricular Lead | Individual Sentus QP Adverse Event Rates | Extracardiac Stimulation | 0.17 percentage of participants |
| Sentus QP Left Ventricular Lead | Individual Sentus QP Adverse Event Rates | Mechanical Lead Failure | 0.12 percentage of participants |
| Sentus QP Left Ventricular Lead | Individual Sentus QP Adverse Event Rates | Elevated Lead Impedance | 0.12 percentage of participants |
| Sentus QP Left Ventricular Lead | Individual Sentus QP Adverse Event Rates | Elevated LV Pacing Threshold | 0.06 percentage of participants |
| Sentus QP Left Ventricular Lead | Individual Sentus QP Adverse Event Rates | Electrical Lead Failure | 0.06 percentage of participants |
| Sentus QP Left Ventricular Lead | Individual Sentus QP Adverse Event Rates | Cardiac Perforation | 0.06 percentage of participants |
Secondary
Number of Participants Successfully Reprogrammed to Resolve Phrenic Nerve Stimulation or High Pacing Threshold
The purpose of this secondary endpoint is to evaluate the number of participants in whom phrenic nerve stimulation or high LV pacing threshold was be successfully resolved by reprogramming of the LV pacing vector. This is evaluated as the number of participants with successful reprogramming out of all participants experiencing phrenic nerve stimulation or high LV pacing threshold. LV pacing threshold resulting in invasive intervention, or, in the absence of intervention, a lead threshold that has increased two fold from the chronic threshold value, and is unable to achieve a 2:1 safety margin at follow-up is considered a high LV pacing threshold.
Time frame: 12 months
Population: All participants in the Pre-Market cohort, defined as the study participants who were consented and implanted with a Sentus QP LV lead on or before January 29, 2016, and whom experienced phrenic nerve stimulation or high LV pacing threshold.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sentus QP Left Ventricular Lead | Number of Participants Successfully Reprogrammed to Resolve Phrenic Nerve Stimulation or High Pacing Threshold | 73 Participants |
Secondary
Sentus QP Acceptable Pacing Impedance at 3 Months Per Lead Model
The purpose of this secondary endpoint is to evaluate the acceptable LV lead pacing impedance at 3 months post-implantation. This was evaluated as the number of participants with an acceptable LV pacing impedance out of the total participants. LV impedance values of greater than 200 Ohms and less than 2000 Ohms is considered acceptable.
Time frame: 3 months
Population: All participants in the Pre-Market cohort, defined as the study participants who were consented and implanted with a Sentus QP LV lead on or before January 29, 2016, and with completed impedance testing at 3 months post-implant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sentus QP Left Ventricular Lead | Sentus QP Acceptable Pacing Impedance at 3 Months Per Lead Model | 245 Participants |
| Sentus QP S Model Left Ventricular Lead | Sentus QP Acceptable Pacing Impedance at 3 Months Per Lead Model | 36 Participants |
Secondary
Sentus QP Acceptable Pacing Threshold in Novel Vectors at 3 Months
The purpose of this secondary endpoint is to evaluate the number of participants with at least one acceptable LV lead pacing threshold in a novel pacing vector at 3 months post-implantation. This was evaluated as the number of participants with at least one acceptable LV pacing threshold in a novel pacing vector out of the total number of participants with completed novel pacing threshold testing. LV threshold values of less than or equal to 2.5 V at 0.4 ms in a novel pacing vector is considered acceptable.
Time frame: 3 months
Population: All participants in the Pre-Market cohort, defined as the study participants who were consented and implanted with a Sentus QP LV lead on or before January 29, 2016, and with completed novel vector threshold testing at 3 months post-implant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sentus QP Left Ventricular Lead | Sentus QP Acceptable Pacing Threshold in Novel Vectors at 3 Months | 261 Participants |
Secondary
Sentus QP Acceptable Pacing Threshold in Permanently Programmed Vector at 3 Months Per Lead Model
The purpose of the secondary endpoint is to evaluate the LV lead pacing threshold for the permanently programmed pacing vector at 3 months post-implantation in the two different lead types, Sentus OTW QP L and Sentus OTW QP S. This was evaluated as the number of participants with an acceptable pacing threshold out of the total number of patients for each lead model. LV threshold values of less than or equal to 2.5 V at 0.4 ms in the permanently programmed vector is considered acceptable.
Time frame: 3 months
Population: All participants in the Pre-Market cohort, defined as the study participants who were consented and implanted with a Sentus QP LV lead on or before January 29, 2016, and with completed threshold testing at 3 months post-implant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sentus QP Left Ventricular Lead | Sentus QP Acceptable Pacing Threshold in Permanently Programmed Vector at 3 Months Per Lead Model | 226 Participants |
| Sentus QP S Model Left Ventricular Lead | Sentus QP Acceptable Pacing Threshold in Permanently Programmed Vector at 3 Months Per Lead Model | 32 Participants |
Secondary
Sentus QP Acceptable R-wave Sensed Amplitude at 3 Months Per Lead Model
The purpose of this secondary endpoint is to evaluate acceptable LV lead sensing amplitude at 3 months post-implantation. This was evaluated as the number of participants with an acceptable LV sensing amplitude out of the total number of participants. R-wave sensed mean amplitude of greater than or equal to 2 mV is considered acceptable.
Time frame: 3 months
Population: All participants in the Pre-Market cohort, defined as the study participants who were consented and implanted with a Sentus QP LV lead on or before January 29, 2016, and with completed sensing test at 3 months post-implant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sentus QP Left Ventricular Lead | Sentus QP Acceptable R-wave Sensed Amplitude at 3 Months Per Lead Model | 223 Participants |
| Sentus QP S Model Left Ventricular Lead | Sentus QP Acceptable R-wave Sensed Amplitude at 3 Months Per Lead Model | 32 Participants |
Secondary
Sentus QP Related Complication-free Rate Per Lead Model
The purpose of secondary endpoint 7 is to evaluate the Sentus QP related complication-free rate through study termination (post approval phase). This is evaluated as percentage of participants without a complication per lead model.
Time frame: Up to 4 years
Population: All participants in the Post-Market cohort, which included all participants who were enrolled with planned 5 year follow-up and were successfully implanted with a Sentus QP left ventricular lead.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sentus QP Left Ventricular Lead | Sentus QP Related Complication-free Rate Per Lead Model | 98.47 percentage of participants |
| Sentus QP S Model Left Ventricular Lead | Sentus QP Related Complication-free Rate Per Lead Model | 96.67 percentage of participants |
Secondary
Sentus QP Time to Complication
The purpose of this secondary is to evaluate the Sentus related complication-free rate through 6 months post-implant by the Kaplan-Meier method. The below table shows Kaplan-Meier estimates of the estimated freedom from Sentus related complications at 180 days.
Time frame: 6 months
Population: All participants in the Pre-Market cohort, defined as the study participants who were consented and implanted with a Sentus QP LV lead on or before January 29, 2016.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sentus QP Left Ventricular Lead | Sentus QP Time to Complication | 97.1 percentage of participants |