Trial Outcomes & Findings for MultiPoint Pacing IDE Study (NCT NCT01786993)

Last Updated: 2019-02-04

Results Overview

A system related complication is a complication related to the Quadripolar CRT-D device system which includes pulse generator and leads, as adjudicated by an independent Clinical Events Committee (CEC). All subjects who had an attempted implant or a successful Quadripolar system implant were included in the analysis of this safety endpoint.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

506 participants

Primary outcome timeframe

Implant to 9 months

Results posted on

2019-02-04

Participant Flow

The study enrolled 506 subjects at 49 investigational centers located in the U.S. A patient was considered enrolled upon signing informed consent. The first subject was enrolled on April 25, 2013. The study was double-blinded (the study subjects and the authorized personnel conducting the NYHA Class and Patient Global assessments were blinded).

455 out of 469 subjects with an attempted implant (97% success rate) received Quadripolar BiV pacing between implant and 3 months. At 3 months, responder status was assessed per Clincial Composite Score and 1:1 randomziation was stratified by responder status. 381 patients were randomized to either BiV (n = 180) or MPP (n = 201) at 3 months.

Participant milestones

Participant milestones
Measure	Multi-point Pacing Arm Subjects were programmed to MPP between 3 and 9 months. MPP programming was stipulated by the Echocardiographic measurements (e.g. EA VTI) during an acute hemodynamic assessment at the 3-month visit in the MPP IDE study.	Biventricular Arm Subjects were programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.
Overall Study STARTED	201	180
Overall Study Per Protocol Population at 9 Months	189	170
Overall Study COMPLETED	189	170
Overall Study NOT COMPLETED	12	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Multi-point Pacing Arm Subjects were programmed to MPP between 3 and 9 months. MPP programming was stipulated by the Echocardiographic measurements (e.g. EA VTI) during an acute hemodynamic assessment at the 3-month visit in the MPP IDE study.	Biventricular Arm Subjects were programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.
Overall Study Death	6	7
Overall Study Withdrawal by Subject	3	2
Overall Study Lost to Follow-up	0	1
Overall Study Subject Non-Compliance	1	0
Overall Study System Explant	1	0
Overall Study Hospice Admission	1	0

Baseline Characteristics

MultiPoint Pacing IDE Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MultiPoint Pacing Arm n=201 Participants Subjects were programmed to MPP between 3 and 9 months. MPP programming was stipulated by the Echocardiographic measurements (e.g. EA VTI) during an acute hemodynamic assessment at the 3-month visit in the MPP IDE study.	Biventricular Arm n=180 Participants Subjects were programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.	Total n=381 Participants Total of all reporting groups
Age, Continuous	67 years STANDARD_DEVIATION 10 • n=5 Participants	68 years STANDARD_DEVIATION 10 • n=7 Participants	68 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	73 Participants n=5 Participants	61 Participants n=7 Participants	134 Participants n=5 Participants
Sex: Female, Male Male	128 Participants n=5 Participants	119 Participants n=7 Participants	247 Participants n=5 Participants
Region of Enrollment United States	201 participants n=5 Participants	180 participants n=7 Participants	381 participants n=5 Participants
Ethnicity Hispanic or Latino	10 participants n=5 Participants	5 participants n=7 Participants	15 participants n=5 Participants
Ethnicity Non-Hispanic or Latino	191 participants n=5 Participants	175 participants n=7 Participants	366 participants n=5 Participants
RACE White	176 participants n=5 Participants	163 participants n=7 Participants	339 participants n=5 Participants
RACE Black or African American	19 participants n=5 Participants	16 participants n=7 Participants	35 participants n=5 Participants
RACE Asian	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
RACE Other	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
QRS Duration	158 ms STANDARD_DEVIATION 24 • n=5 Participants	154 ms STANDARD_DEVIATION 20 • n=7 Participants	156 ms STANDARD_DEVIATION 22 • n=5 Participants
QRS Morphology Left Bundle Branch Block (LBBB)	146 participants n=5 Participants	139 participants n=7 Participants	285 participants n=5 Participants
QRS Morphology Right Bundle Branch Block (RBBB)	21 participants n=5 Participants	20 participants n=7 Participants	41 participants n=5 Participants
QRS Morphology Interventricular Conduction Delay (IVCD)	32 participants n=5 Participants	21 participants n=7 Participants	53 participants n=5 Participants
QRS Morphology Unknown	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Cardiomyopathy Etiology Ischemic	96 participants n=5 Participants	88 participants n=7 Participants	184 participants n=5 Participants
Cardiomyopathy Etiology Non-ischemic	103 participants n=5 Participants	91 participants n=7 Participants	194 participants n=5 Participants
Cardiomyopathy Etiology None	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Implant to 9 months

Population: Of 469 subjects who underwent an attempted implant, 31 subjects experienced a system-related complication between implant and 9 months (13 were LV lead-related, 16 were RA/RV lead-related and 3 were Quadripolar CRT-D pulse generator related. One subject experienced more than one category of complication).

Outcome measures

Outcome measures
Measure	BiV/MPP Patients n=469 Participants Of 469 subjects who underwent an attempted implant, 31 subjects experienced a system-related complication between implant and 9 months (13 were LV lead-related, 16 were RA/RV lead-related and 3 were Quadripolar CRT-D pulse generator related. One subject experienced more than one category of complication).	Biventricular Arm Traditional Biventricular Pacing Traditional Biventricular Pacing: Subjects are programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.
Freedom From System-related Complications Through 9 Months Compared to an Objective Performance Criterion	0.932 Event-Free Probability Interval 0.904 to 0.951	—

PRIMARY outcome

Timeframe: 3 months to 9 months

The hypothesis is that the non-response rate to CRT therapy in the MPP therapy arm is not inferior to the non-response rate in the BiV arm between 3 and 9 months post-implant. Responder status was assessed using the Clinical Composite Score (CCS). A patient's CCS was classified as worsened, improved or unchanged based on the definitions below: * Worsened - patient died due to cardiovascular reasons, experienced a HF event, demonstrated worsening in NYHA class, or had worsening of PGA score compared to the last observation * Improved - patient survived without a HF event, and demonstrated either improvement in NYHA class or improvement in PGA score, or both compared to the last observation. * Unchanged - patient was neither improved nor worsened For patients who were responders at the 3-month visit, those who were "Improved" and "Unchanged" between 3 and 9 months were classified as responders, whereas those who were "Worsened" were grouped together as non-responders.

Outcome measures

Outcome measures
Measure	BiV/MPP Patients n=201 Participants Of 469 subjects who underwent an attempted implant, 31 subjects experienced a system-related complication between implant and 9 months (13 were LV lead-related, 16 were RA/RV lead-related and 3 were Quadripolar CRT-D pulse generator related. One subject experienced more than one category of complication).	Biventricular Arm n=180 Participants Traditional Biventricular Pacing Traditional Biventricular Pacing: Subjects are programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.
Percentage of Non-responders With MPP Compared to Biventricular Pacing	29.9 percentage of patients	25 percentage of patients

Adverse Events

MultiPoint Pacing Arm

Serious events: 4 serious events

Other events: 40 other events

Deaths: 0 deaths

Biventricular Arm

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MultiPoint Pacing Arm n=201 participants at risk Subjects were programmed to MPP between 3 and 9 months. MPP programming was stipulated by the Echocardiographic measurements (e.g. EA VTI) during an acute hemodynamic assessment at the 3-month visit in the MPP IDE study.	Biventricular Arm n=180 participants at risk Subjects were programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.
Cardiac disorders LV Lead Dislodgement or Migration	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	1.7% 3/180 • Number of events 3 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders RA/RV Lead Dislodgement or Migration	0.50% 1/201 • Number of events 2 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Pulse Generator Erosion/Extrusion	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Generator Malfunction	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).

Other adverse events

Additional Information

Director of Clinical Studies

St. Jude Medical

Phone: 972-309-8000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	MultiPoint Pacing Arm n=201 participants at risk Subjects were programmed to MPP between 3 and 9 months. MPP programming was stipulated by the Echocardiographic measurements (e.g. EA VTI) during an acute hemodynamic assessment at the 3-month visit in the MPP IDE study.	Biventricular Arm n=180 participants at risk Subjects were programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.
Cardiac disorders LV Lead Elevated Pacing Thresholds	1.5% 3/201 • Number of events 3 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders LV Lead Loss of Capture	1.00% 2/201 • Number of events 2 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Phrenic Nerve/Diaphragmatic Stimulation Related to LV Lead	10.4% 21/201 • Number of events 25 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Rise in Threshold And Exit Block Related to LV Lead	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders RA/RV Lead Elevated Pacing Thresholds	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders RA/RV Lead Loss of Capture	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders RA/RV Lead Oversensing	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	1.1% 2/180 • Number of events 2 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Artifact Observed on Atrial Channel	5.0% 10/201 • Number of events 10 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Discomfort Around Device	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Intolerance to MPP Pacing	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Pulse Generator Oversensing	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	1.1% 2/180 • Number of events 2 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Pacemaker Mediated Tachycardia (PMT)	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Intolerance to BiV Pacing	0.00% 0/201 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.56% 1/180 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Thrombo-Embolic Event	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Erythema to Lateral Aspect of Incision Site	0.00% 0/201 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.56% 1/180 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).
Cardiac disorders Pericardial Effusion	0.50% 1/201 • Number of events 1 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).	0.00% 0/180 • 3-month randomization to 9 months * Serious Adverse Events: Events that require invasive intervention (e.g. lead dislodgment requiring repositioning). * Other Adverse Events: Events that can be managed without invasive intervention (e.g., oversensing or loss of pacing capture, which is remedied by reprogramming of the pulse generator).