MPP IDE: MultiPoint Pacing IDE Study

• Sponsor: Abbott Medical Devices (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01786993
• Collaborator: (none)
• Enrollment: 506
• Locations: 49
• Arms: 2
• Actual Duration (Months): 38
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This IDE study is a prospective, randomized, double-blind, multi-center clinical study to evaluate the safety and efficacy of patient treatment with MPP compared to patient treatment with standard BiV pacing at 9 months.

The study will be conducted at a maximum of 50 investigational centers located in the United States. A maximum of 506 subjects implanted with the Quadripolar cardiac resynchronization therapy device (CRT-D) system will be enrolled in the study.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Device: MultiPoint Pacing; Device: Traditional Biventricular Pacing	Phase 3

Detailed Description

All subjects will undergo a 2 dimensional Echocardiogram within the 30 days prior to implant, and again at 3, 6 and 9 months post implant. At implant, the final LV pacing configuration is programmed using any one of the 10 available pacing vectors. The paced/sensed atrioventricular (AV) and interventricular (VV) delays may be optimized as per the site's standard of care. Subjects will continue to receive BiV therapy until the 3-month follow-up visit.

At the 3-month visit, responder status between Enrollment and 3 months will be assessed using the Clinical Composite Score (CCS). All subjects that are "Improved" using the definition outlined in the CCS will be grouped together as Responders. All subjects that are "Worsened" or "Unchanged" using the definitions outlined in the CCS will be considered as Non-responders. All subjects will undergo acute measurement of cardiac performance (e.g., Echocardiography) at various MPP combinations compared to BiV pacing. Only subjects with "equal or better" echocardiographic measurements (i.e., EA VTI measurements) with MPP feature on compared to BiV pacing will be randomized in a 1:1 ratio to one of the two arms - BiV arm or MPP arm.

At the 9-month visit, responder status will be evaluated once again using the CCS and compared to the status at 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 506 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: MultiPoint Pacing IDE Study
• Actual Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Multi-point pacing arm MultiPoint Pacing	Device: MultiPoint Pacing; Subjects are programmed to MPP between 3 and 9 months. MPP programming is stipulated by the Echocardiographic measurements (e.g. EA VTI) during an acute hemodynamic assessment at the 3-month visit in the MPP IDE study.
Active Comparator: Biventricular arm Traditional Biventricular Pacing	Device: Traditional Biventricular Pacing; Subjects are programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.

Outcome Measures

Primary Outcome Measures

1. Freedom From System-related Complications Through 9 Months Compared to an Objective Performance Criterion [Implant to 9 months]

   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.

2. Percentage of Non-responders With MPP Compared to Biventricular Pacing [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meets current clinical indication for implantation of a cardiac resynchronization therapy system for treatment of heart failure or life-threatening ventricular tachyarrhythmia(s)

• Receiving a new CRT implant or undergoing an upgrade from an existing ICD or pacemaker implant with no prior LV lead placement

• Have the ability to provide informed consent for study participation and are willing and able to comply with the prescribed follow-up tests and schedule of evaluations

Exclusion Criteria:

• Have had a recent Cerebrovascular Accident (CVA) or Transient Ischemic Attack (TIA) within 3 months of enrollment

• Have an existing Class I recalled lead

• Have a hypersensitivity to a single 1.0mg dose of dexamethasone sodium phosphate

• Have a classification of Status 1 for cardiac transplantation or consideration for transplantation over the next 9 months

• Have permanent atrial fibrillation (AF)

• Have undergone a cardiac transplantation within 40 days of enrollment

• Have had a recent myocardial infarction, unstable angina within 40 days or cardiac revascularization within 3 months of implant.

• Are currently participating in a clinical investigation that includes an active treatment arm

• Are pregnant or planning to become pregnant during the duration of the study

• Have a life expectancy of less than 9 months due to any condition

• Are less than 18 years of age

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Heart Center Research, LLC.	Huntsville	Alabama	United States	35801
2	Banner Heart Hospital	Mesa	Arizona	United States	85027
3	Arkansas Heart Hospital	Little Rock	Arkansas	United States	72211
4	Glendale Memorial Hospital and Medical Center	Glendale	California	United States	91206
5	Scripps Green Hospital	La Jolla	California	United States	92037
6	Premier Cardiology, Inc	Newport Beach	California	United States	92663
7	Regional Cardiology Associates	Sacramento	California	United States	95819
8	Sutter Memorial Hospital	Sacramento	California	United States	95819
9	Colorado Heart & Vascular, P.C.	Lakewood	Colorado	United States	80228
10	Cardiology Associates of Fairfield County, PC	Norwalk	Connecticut	United States	06851
11	Christiana Hospital	Newark	Delaware	United States	19718
12	Bay Area Cardiology Associates PA	Brandon	Florida	United States	33511
13	Watson Clinic Center	Lakeland	Florida	United States	33805
14	Florida Hospital Orlando	Orlando	Florida	United States	32803
15	Sarasota Memorial Hospital	Sarasota	Florida	United States	34239
16	St. Joseph's Hospital	Atlanta	Georgia	United States	30342
17	HeartCare Midwest	Peoria	Illinois	United States	61614
18	Central Baptist Hospital	Lexington	Kentucky	United States	40503
19	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
20	Lahey Clinic Medical Center	Burlington	Massachusetts	United States	01805
21	Thoracic Cardio Healthcare Foundation	Lansing	Michigan	United States	48910
22	Jackson Heart Clinic	Jackson	Mississippi	United States	39216
23	North Mississippi Medical Center	Tupelo	Mississippi	United States	38801
24	St. Luke's Hospital	Kansas City	Missouri	United States	64111
25	Mercy Hospital St. Louis	Saint Louis	Missouri	United States	63141
26	Deborah Heart and Lung Center	Browns Mills	New Jersey	United States	08015
27	Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
28	Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
29	New Mexico Heart Institute	Albuquerque	New Mexico	United States	87102
30	New York Presbyterian Hospital/Cornell University	New York	New York	United States	10021
31	University of Rochester Medical Center	Rochester	New York	United States	14642
32	Novant Health Heart and Vascular Research Institute	Charlotte	North Carolina	United States	28204
33	Wake Forest University Medical Center Clinical Sciences	Winston-Salem	North Carolina	United States	27157
34	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
35	Ohio Health Research Institute	Columbus	Ohio	United States	43124
36	The Toledo Hospital	Toledo	Ohio	United States	43606
37	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17602
38	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
39	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
40	WellSpan Health	York	Pennsylvania	United States	17403
41	Medical University of South Carolina	Charleston	South Carolina	United States	29425
42	St. Thomas Hospital	Nashville	Tennessee	United States	37205
43	Vanderbilt Heart and Vascular Institute	Nashville	Tennessee	United States	37232
44	Cardiology Center of Amarillo, L.L.P	Amarillo	Texas	United States	79106
45	Austin Heart	Austin	Texas	United States	78756
46	South Texas Cardiovascular Consultants	San Antonio	Texas	United States	78201
47	Cardiovascular Associates, LTD	Virginia Beach	Virginia	United States	23454
48	Aurora Medical Group	Milwaukee	Wisconsin	United States	53215
49	Aspirus Wausau Hospital	Wausau	Wisconsin	United States	54401

Sponsors and Collaborators

• Abbott Medical Devices

Investigators

• Principal Investigator: Gery Tomassoni, MD, Central Baptist Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abbott Medical Devices
• ClinicalTrials.gov Identifier: NCT01786993
• Other Study ID Numbers: 60029161/D
• First Posted: Feb 8, 2013
• Last Update Posted: Feb 4, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Recruitment Details	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).
Pre-assignment Detail	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.

Arm/Group Title	Multi-point Pacing Arm	Biventricular Arm
Arm/Group Description	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.	Subjects were programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.
Period Title: Overall Study
STARTED	201	180
Per Protocol Population at 9 Months	189	170
COMPLETED	189	170
NOT COMPLETED	12	10

Baseline Characteristics

Arm/Group Title	MultiPoint Pacing Arm	Biventricular Arm	Total
Arm/Group Description	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.	Subjects were programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.	Total of all reporting groups
Overall Participants	201	180	381
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67 (10)	68 (10)	68 (10)
Sex: Female, Male (Count of Participants)
Female	73 36.3%	61 33.9%	134 35.2%
Male	128 63.7%	119 66.1%	247 64.8%
Region of Enrollment (participants) [Number]
United States	201 100%	180 100%	381 100%
Ethnicity (participants) [Number]
Hispanic or Latino	10 5%	5 2.8%	15 3.9%
Non-Hispanic or Latino	191 95%	175 97.2%	366 96.1%
RACE (participants) [Number]
White	176 87.6%	163 90.6%	339 89%
Black or African American	19 9.5%	16 8.9%	35 9.2%
Asian	2 1%	0 0%	2 0.5%
Other	4 2%	1 0.6%	5 1.3%
QRS Duration (ms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ms]	158 (24)	154 (20)	156 (22)
QRS Morphology (participants) [Number]
Left Bundle Branch Block (LBBB)	146 72.6%	139 77.2%	285 74.8%
Right Bundle Branch Block (RBBB)	21 10.4%	20 11.1%	41 10.8%
Interventricular Conduction Delay (IVCD)	32 15.9%	21 11.7%	53 13.9%
Unknown	2 1%	0 0%	2 0.5%
Cardiomyopathy Etiology (participants) [Number]
Ischemic	96 47.8%	88 48.9%	184 48.3%
Non-ischemic	103 51.2%	91 50.6%	194 50.9%
None	2 1%	1 0.6%	3 0.8%

Outcome Measures

1. Primary Outcome

Title	Freedom From System-related Complications Through 9 Months Compared to an Objective Performance Criterion
Description	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.
Time Frame	Implant to 9 months

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	BiV/MPP Patients
Arm/Group Description	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).
Measure Participants	469
Number (95% Confidence Interval) [Event-Free Probability]	0.932

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BiV/MPP Patients
	Comments	The hypothesis is formally expressed as: H0: Freedom from system-related complications through 9 months ≤ 75% Ha: Freedom from system-related complications through 9 months > 75%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Event-Free Probability
	Estimated Value	0.932
	Confidence Interval	(2-Sided) 95%; 0.904 to 0.951
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Non-responders With MPP Compared to Biventricular Pacing
Description	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.
Time Frame	3 months to 9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MultiPoint Pacing Arm	Biventricular Arm
Arm/Group Description	MultiPoint Pacing MultiPoint Pacing: Subjects are programmed to MPP between 3 and 9 months. MPP programming is stipulated by the Echocardiographic measurements (e.g. EA VTI) during an acute hemodynamic assessment at the 3-month visit in the MPP IDE study.	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.
Measure Participants	201	180
Number [percentage of patients]	29.9	25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BiV/MPP Patients, Biventricular Arm
	Comments	H0: (Non-responder rate in the BiV arm between 3 M randomization and 9 M) - (Non-responder rate in the MPP arm between 3 M randomization and 9 M) ≤ -0.15 Ha: (Non-responder rate in the BiV arm between 3 M randomization and 9 M) - (Non-responder rate in the MPP arm between 3 M randomization and 9 M) > -0.15 The null hypothesis will be rejected at the 2.5% significance level if the lower one-sided 97.5% confidence bound for the difference in the proportions is above -0.15.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assuming a binomial distribution with a 44% probability for non-responders between 3 months and 9 months in both study arms, the sample size required for 85% power to reject the null hypothesis at the 5% significance level is 394. To adjust for a potential net crossover of 15% and an overall attrition rate of 20%, the total number of patients required to be enrolled in this study is 506.
Statistical Test of Hypothesis	p-Value	0.0131
	Comments
	Method	normal approximation for binomial dist
	Comments
Method of Estimation	Estimation Parameter	Difference of proportions
	Estimated Value	-0.049
	Confidence Interval	(1-Sided) 97.5%; -0.138 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	3-month randomization to 9 months
Adverse Event Reporting Description	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).
Arm/Group Title	MultiPoint Pacing Arm		Biventricular Arm
Arm/Group Description	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.		Subjects were programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.
All Cause Mortality
	MultiPoint Pacing Arm		Biventricular Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	MultiPoint Pacing Arm		Biventricular Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/201 (2%)		3/180 (1.7%)
Cardiac disorders
LV Lead Dislodgement or Migration	1/201 (0.5%)	1	3/180 (1.7%)	3
RA/RV Lead Dislodgement or Migration	1/201 (0.5%)	2	0/180 (0%)	0
Pulse Generator Erosion/Extrusion	1/201 (0.5%)	1	0/180 (0%)	0
Generator Malfunction	1/201 (0.5%)	1	0/180 (0%)	0
Other (Not Including Serious) Adverse Events
	MultiPoint Pacing Arm		Biventricular Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/201 (19.9%)		5/180 (2.8%)
Cardiac disorders
LV Lead Elevated Pacing Thresholds	3/201 (1.5%)	3	0/180 (0%)	0
LV Lead Loss of Capture	2/201 (1%)	2	0/180 (0%)	0
Phrenic Nerve/Diaphragmatic Stimulation Related to LV Lead	21/201 (10.4%)	25	0/180 (0%)	0
Rise in Threshold And Exit Block Related to LV Lead	1/201 (0.5%)	1	0/180 (0%)	0
RA/RV Lead Elevated Pacing Thresholds	1/201 (0.5%)	1	0/180 (0%)	0
RA/RV Lead Loss of Capture	1/201 (0.5%)	1	0/180 (0%)	0
RA/RV Lead Oversensing	1/201 (0.5%)	1	2/180 (1.1%)	2
Artifact Observed on Atrial Channel	10/201 (5%)	10	0/180 (0%)	0
Discomfort Around Device	1/201 (0.5%)	1	0/180 (0%)	0
Intolerance to MPP Pacing	1/201 (0.5%)	1	0/180 (0%)	0
Pulse Generator Oversensing	1/201 (0.5%)	1	2/180 (1.1%)	2
Pacemaker Mediated Tachycardia (PMT)	1/201 (0.5%)	1	0/180 (0%)	0
Intolerance to BiV Pacing	0/201 (0%)	0	1/180 (0.6%)	1
Thrombo-Embolic Event	1/201 (0.5%)	1	0/180 (0%)	0
Erythema to Lateral Aspect of Incision Site	0/201 (0%)	0	1/180 (0.6%)	1
Pericardial Effusion	1/201 (0.5%)	1	0/180 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.