QP ExCELs: MultiPole Pacing (MPP) Sub-Study

• Sponsor: Biotronik, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03155724
• Collaborator: (none)
• Enrollment: 53
• Locations: 44
• Arm: 1
• Actual Duration (Months): 32.2
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Device: MultiPole Pacing	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: QP ExCELs: MultiPole Pacing (MPP) Sub-Study
• Actual Study Start Date: May 19, 2017
• Actual Primary Completion Date: Jan 23, 2020
• Actual Study Completion Date: Jan 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MultiPole Pacing Traditional biventricular pacing CRT non-responders at the 3 or 6 month QP ExCELs study follow-up.	Device: MultiPole Pacing; CRT non-responders are programmed with MultiPole pacing ON.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

2. 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")

3. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thomas Hospital	Fairhope	Alabama	United States	36532
2	South Bay Electrophysiology	Inglewood	California	United States	90301
3	Eisenhower Desert Cardiology	Rancho Mirage	California	United States	92270
4	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
5	Florida Hospital	Orlando	Florida	United States	32803
6	Orlando Health Heart Institute	Orlando	Florida	United States	32806
7	Florida Hospital Tampa Pepin Heart Institute	Tampa	Florida	United States	33613
8	Piedmont Heart Institute	Atlanta	Georgia	United States	30309
9	University of Chicago Medical Center	Chicago	Illinois	United States	60637
10	Parkview Physicians Group - Cardiology	Fort Wayne	Indiana	United States	46845
11	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
12	University of Kansas Hospital	Kansas City	Kansas	United States	66160
13	Baptist Health - Lexington	Lexington	Kentucky	United States	40503
14	University of Kentucky	Lexington	Kentucky	United States	40536
15	Northeast Cardiology	Bangor	Maine	United States	04401
16	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
17	Southcoast Health	Fall River	Massachusetts	United States	02720
18	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
19	University of Michigan Hospital	Ann Arbor	Michigan	United States	48109
20	Henry Ford Hospital	Detroit	Michigan	United States	48202
21	Michigan Heart	Ypsilanti	Michigan	United States	48197
22	Cardiology Associates of North Mississippi	Tupelo	Mississippi	United States	38801
23	SSM Health St. Joseph Hospital - St. Charles	Saint Charles	Missouri	United States	63301
24	St. Louis Heart and Vascular	Saint Louis	Missouri	United States	63136
25	Mercy Clinic Cardiology	Springfield	Missouri	United States	65804
26	Glacier View Medical Research Institute, Cardiology	Kalispell	Montana	United States	59901
27	Jersey Shore University Medical Center	Neptune	New Jersey	United States	07753
28	Montefiore Medical Center	Bronx	New York	United States	10467
29	New York Presbyterian Queens	Flushing	New York	United States	11355
30	Weill Cornell Medicine	New York	New York	United States	10021
31	Mt. Sinai St. Luke's Hospital	New York	New York	United States	10025
32	Westchester Medical Center	Valhalla	New York	United States	10595
33	Asheville Cardiology Associates	Asheville	North Carolina	United States	28803
34	Novant Health Winston-Salem Cardiology	Winston-Salem	North Carolina	United States	27103
35	Wake Forest Baptist Health Medical Center	Winston-Salem	North Carolina	United States	27157
36	Sanford Medical Center - Fargo	Fargo	North Dakota	United States	58102
37	University of Cincinnati	Cincinnati	Ohio	United States	45219
38	Temple Heart and Vascular Institute	Philadelphia	Pennsylvania	United States	19140
39	Upstate Cardiology	Greenville	South Carolina	United States	29607
40	UT Erlanger Cardiology	Chattanooga	Tennessee	United States	37403
41	Fort Worth Heart	Fort Worth	Texas	United States	76104
42	UT Health Science Center	The Woodlands	Texas	United States	77380
43	University of Utah Medical Center	Salt Lake City	Utah	United States	84132
44	UVM Medical	Burlington	Vermont	United States	05401

Sponsors and Collaborators

• Biotronik, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 6, 2019

More Information

Publications

None provided.

• Responsible Party: Biotronik, Inc.
• ClinicalTrials.gov Identifier: NCT03155724
• Other Study ID Numbers: MPP Sub-Study
• First Posted: May 16, 2017
• Last Update Posted: Mar 8, 2021
• Last Verified: Feb 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Arm/Group Title	MultiPole Pacing
Arm/Group Description	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.
Period Title: Overall Study
STARTED	53
COMPLETED	42
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	MultiPole Pacing
Arm/Group Description	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.
Overall Participants	53
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	69.3 (12.13)
Sex: Female, Male (Count of Participants)
Female	11 20.8%
Male	42 79.2%
Race and Ethnicity Not Collected (Count of Participants)
Height (in) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [in]	68.5 (4.0)
Weight (Pounds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Pounds]	212.7 (52.69)

Outcome Measures

1. Primary Outcome

Title	Cardiac Resynchronization Therapy (CRT) Responder Status With the MPP Feature
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	MultiPole Pacing
Arm/Group Description	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.
Measure Participants	45
Improved	16 30.2%
Unchanged	23 43.4%
Worsened	6 11.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MultiPole Pacing
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Exact, binomial, one-sided
	Comments

2. Secondary Outcome

Title	Percentage of Participants Without MPP System Related Adverse Events Requiring Additional Invasive Intervention to Resolve at 6 Months.
Description	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

Outcome Measure Data

Analysis Population Description

Evaluable participants for Secondary Endpoint 1 include all participants who have been enrolled into the MPP Sub-Study.

Arm/Group Title	MultiPole Pacing
Arm/Group Description	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.
Measure Participants	53
Number (95% Confidence Interval) [percentage of participants]	100 188.7%

3. Secondary Outcome

Title	Clinical Composite Score (CCS) + Patient Global Assessment (PGA) Responder Status Utilizing a Modified CCS That Incorporates the PGA
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	MultiPole Pacing
Arm/Group Description	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.
Measure Participants	45
Improved	27 50.9%
Unchanged	11 20.8%
Worsened	7 13.2%

4. Secondary Outcome

Title	CCS Responder Status Utilizing an Expanded Responder Classification
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	MultiPole Pacing
Arm/Group Description	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.
Measure Participants	45
Responder	39 73.6%
Non-Responder	6 11.3%

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	Sites were required to report any cardiovascular hospitalizations and any other hospitalizations in which cardiovascular symptoms occur on or before the date of the MPP 6-Month follow-up. These hospitalizations were categorized as Heart Failure Hospitalization, Non-Heart Failure Hospitalization, or if applicable, Non-system related/non-protocol defined. Extracardiac stimulation was assessed/categorized however other specific adverse event terms were not assessed.
Arm/Group Title	MultiPole Pacing
Arm/Group Description	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.
All Cause Mortality
	MultiPole Pacing
	Affected / at Risk (%)	# Events
Total	3/53 (5.7%)
Serious Adverse Events
	MultiPole Pacing
	Affected / at Risk (%)	# Events
Total	5/53 (9.4%)
Cardiac disorders
Heart Failure Hospitalization	3/53 (5.7%)
General disorders
Non-Heart failure Hospitalization	3/53 (5.7%)
Other (Not Including Serious) Adverse Events
	MultiPole Pacing
	Affected / at Risk (%)	# Events
Total	6/53 (11.3%)
Cardiac disorders
Non-system related/ Non Protocol-defined	2/53 (3.8%)	2
Extracardiac stimulation	4/53 (7.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.