SMARTMSP: Strategic Management to Improve CRT Using Multi-Site Pacing Post Approval Study (Reference # C1918)

• Sponsor: Boston Scientific Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03257436
• Collaborator: (none)
• Enrollment: 586
• Locations: 54
• Arm: 1
• Actual Duration (Months): 34.5
• Patients Per Site: 10.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Prospective, multi-center, single arm, post approval study to be conducted in the United States.

Condition or Disease	Intervention/Treatment	Phase
Left Ventricular Dysfunction	Device: CRT-D	N/A

Detailed Description

Evaluate the effectiveness of Boston Scientific (BSC)'s LV MSP (Left Ventricular MultiSite Pacing) feature in the Resonate family of CRT-D devices and confirm safety in a post approval study when used in accordance with its approved labeling.

Study Design

• Study Type: Interventional
• Actual Enrollment: 586 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Strategic Management to Improve CRT Using Multi-Site Pacing Post Approval Study (Reference # C1918)
• Actual Study Start Date: Jan 5, 2018
• Actual Primary Completion Date: Nov 19, 2020
• Actual Study Completion Date: Nov 19, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: Single Arm General population who receive a Boston Scientific Resonate family of CRT-D device in accordance with its labeled indication for use.	Device: CRT-D; Left Ventricular MultiSite Pacing

Outcome Measures

Primary Outcome Measures

1. LV MSP Feature Related Complication-Free Rate [Between 6 month visit and the 12 month visit in non-responders with LV MSP on for any duration.]

   Proportion of subjects free from LVMSP feature related complications at 12 months

2. Proportion of LV MSP Group Subjects With an Improved Clinical Composite Score at 12 Months [12 Month Follow Up]

   Proportion of non-responders with LV MSP enabled at 6 months who were responders at 12 months. Responders were defined as having an Improved Clinical Composite Score at 12 Months.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Subjects who received de novo implantation of BSC's Resonate family of CRT-D devices with the LV MSP feature4 and BSC's ACUITYTM X4 LV Quadripolar leads. A Resonate family of CRT-D device upgrade from previous single or dual chamber pacemaker or ICD implantation is allowed.

2. Subjects must meet BSC labeled indication for CRT-D implantation.

3. Subjects must have a functional RA lead and RV lead implanted

4. Subjects who are willing and capable of providing informed consent

5. Subjects who are willing and capable of participating in all testing/visits associated with this clinical study at an approved clinical study center and at the intervals defined by this protocol

6. Subjects who are age 18 and above, or of legal age to give informed consent specific to state and national law

Exclusion Criteria:

1. Subjects who received LV pacing prior to receiving the Resonate family of CRT-D system implantation.

2. Subjects who received the LV MSP therapy post CRT-D implantation but prior to enrollment

3. Subjects with documented history of permanent AF

4. Subjects with documented permanent complete AV block

5. Subjects who are expected to receive a heart transplant during the 12 months course of the study

6. Subjects with documented life expectancy of less than 12 months

7. Subjects who enrolled in any other concurrent study or registry, with the exception of mandatory national or governmental registry, without prior written approval from BSC

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mobile Infirmary Medical Center	Mobile	Alabama	United States	36604
2	Phoenix Cardiovascular Group	Phoenix	Arizona	United States	85006
3	Cardiology Associates of NEA	Jonesboro	Arkansas	United States	72401
4	Foothill Cardiology Medical Group	Arcadia	California	United States	91007
5	Chula Vista Cardiac Center	Chula Vista	California	United States	91910
6	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
7	Desert Heart Rhythm Consultants	Palm Springs	California	United States	92262
8	Cardiology Associates Medical Group	Ventura	California	United States	93003
9	Yale University School of Medicine	New Haven	Connecticut	United States	06520
10	Delray Medical Center	Delray Beach	Florida	United States	33484
11	UF Health Jacksonville	Jacksonville	Florida	United States	32209
12	Florida Hospital Waterman	Lake Mary	Florida	United States	32746
13	Tallahassee Research Institute	Tallahassee	Florida	United States	32308
14	Augusta University	Augusta	Georgia	United States	30912
15	Alexian Brothers Hospital Network	Elk Grove Village	Illinois	United States	60007
16	Carle Foundation Hospital	Urbana	Illinois	United States	61801
17	Parkview Hospital Inc	Fort Wayne	Indiana	United States	46845
18	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
19	Norton Heart Specialist	Louisville	Kentucky	United States	40205
20	Advanced Cardiovascular Specialists	Shreveport	Louisiana	United States	71105
21	MedStar Heart and Vascular Institute	Baltimore	Maryland	United States	21237
22	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
23	Ascension St. John Hospital & Medical Center	Detroit	Michigan	United States	48236
24	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
25	St. Mary's of Michigan Research Institute at Covenant Medical Ceter	Saginaw	Michigan	United States	48601
26	UMMC- Division of Cardiology	Jackson	Mississippi	United States	39216
27	St. Lukes Hospital	Kansas City	Missouri	United States	64111
28	Billings Clinic	Billings	Montana	United States	59101
29	Methodist Physicians Clinic Heart Consultants	Omaha	Nebraska	United States	68114
30	Deborah Heart and Lung Center	Browns Mills	New Jersey	United States	08015
31	Hackensack University Medical Canter	Hackensack	New Jersey	United States	07601
32	Montefiore Medical Center	Bronx	New York	United States	10467
33	Durham VA medical Center	Durham	North Carolina	United States	27705
34	WakeMed	Raleigh	North Carolina	United States	27610
35	Trihealth- Good Samaritan & Bethesda North Hospitals	Cincinnati	Ohio	United States	45220
36	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
37	St. Elizabeth Youngstown Hospital	Youngstown	Ohio	United States	44501
38	Salem Health	Salem	Oregon	United States	97301
39	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania	United States	19104
40	UPMC Presbyterian	Pittsburgh	Pennsylvania	United States	15213
41	Pinnacle Health Cardiovascular Institute	Wormleysburg	Pennsylvania	United States	17043
42	Berk Cardiologists	Wyomissing	Pennsylvania	United States	19610
43	AnMed Health Clinical Research	Anderson	South Carolina	United States	29621
44	Rapid City Regional Health	Rapid City	South Dakota	United States	75501
45	Stern Cardiovascular Foundation	Germantown	Tennessee	United States	38138
46	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
47	Heartplace, PA	Bedford	Texas	United States	76021
48	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
49	UT Health	Houston	Texas	United States	77030
50	University of Utah	Salt Lake City	Utah	United States	84132
51	University of Virginia	Charlottesville	Virginia	United States	22908
52	Carient Heart and Vascular	Manassas	Virginia	United States	20109
53	Sentara Norfolk General	Norfolk	Virginia	United States	23507
54	St. Mary's Medical Center	Huntington	West Virginia	United States	25702

Sponsors and Collaborators

• Boston Scientific Corporation

Investigators

• Principal Investigator: Saba Samir, University of Pittsburgh Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 15, 2017

More Information

Publications

None provided.

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT03257436
• Other Study ID Numbers: 92050975
• First Posted: Aug 22, 2017
• Last Update Posted: Jan 3, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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.: Yes
• Keywords provided by Boston Scientific Corporation: Pacing
• Additional relevant MeSH terms: Ventricular Dysfunction; Ventricular Dysfunction, Left

Study Results

Participant Flow

Arm/Group Title	Single Arm
Arm/Group Description	General population who receive a Boston Scientific Resonate family of CRT-D device in accordance with its labeled indication for use. CRT-D: Left Ventricular MultiSite Pacing
Period Title: Overall Study
STARTED	584
COMPLETED	489
NOT COMPLETED	95

Baseline Characteristics

Arm/Group Title	Single Arm
Arm/Group Description	General population who receive a Boston Scientific Resonate family of CRT-D device in accordance with its labeled indication for use. CRT-D: Left Ventricular MultiSite Pacing
Overall Participants	583
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.7 (11)
Sex: Female, Male (Count of Participants)
Female	211 36.2%
Male	372 63.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.3%
Asian	2 0.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	95 16.3%
White	460 78.9%
More than one race	10 1.7%
Unknown or Not Reported	14 2.4%
Region of Enrollment (participants) [Number]
United States	583 100%

Outcome Measures

1. Primary Outcome

Title	LV MSP Feature Related Complication-Free Rate
Description	Proportion of subjects free from LVMSP feature related complications at 12 months
Time Frame	Between 6 month visit and the 12 month visit in non-responders with LV MSP on for any duration.

Outcome Measure Data

Analysis Population Description

Subjects who are non-responders at the 6 month follow up and who have LVMSP enabled for for any duration between the 6th and 12 month visit

Arm/Group Title	Single Arm
Arm/Group Description	General population who receive a Boston Scientific Resonate family of CRT-D device in accordance with its labeled indication for use. CRT-D: Left Ventricular MultiSite Pacing
Measure Participants	102
Number (95% Confidence Interval) [percentage of participants]	99 17%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Single Arm
	Comments	The LV MSP feature-related CFR between the 6 Month Visit and the 12 Month Visit was calculated using Kaplan-Meier methodology. H0: LV MSP feature-related complication-free rate between 6 Month Visit and 12 Month Visit ≤ 90%. The sample size of 61 subjects was required to evaluate the Primary Safety Endpoint using an exact test since a power calculation cannot be directly calculated for a one group Kaplan-Meier analysis.
	Type of Statistical Test	Other
	Comments	A power calculation using a sample size of 61 subjects as the non-responders with the LV MSP on was calculated based on a one-sided exact test for a single binomial proportion, using SAS Version 9.4 with the following assumptions: Performance goal = 90% Expected LV MSP feature-related CFR rate between 6 and 12 Month Visit = 98% Significance level = 5% Power = 80%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Kaplan Meir Methodology
	Estimated Value	99
	Confidence Interval	(1-Sided) 95%; 94.1 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Proportion of LV MSP Group Subjects With an Improved Clinical Composite Score at 12 Months
Description	Proportion of non-responders with LV MSP enabled at 6 months who were responders at 12 months. Responders were defined as having an Improved Clinical Composite Score at 12 Months.
Time Frame	12 Month Follow Up

Outcome Measure Data

Analysis Population Description

Non-responders at 6 Months who had LV MSP enabled and had complete clinical composite score data, LV MSP on and achieved >93% LVa and LVb pacing

Arm/Group Title	Single Arm
Arm/Group Description	General population who receive a Boston Scientific Resonate family of CRT-D device in accordance with its labeled indication for use. CRT-D: Left Ventricular MultiSite Pacing
Measure Participants	78
Number (95% Confidence Interval) [percentage of participants]	51.3 8.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Single Arm
	Comments	The effectiveness endpoint for SMART MSP PAS is the proportion of the LV MSP Group with an Improved CCS. For this endpoint, those subjects in the LV MSP Group that become responders will be defined as having an Improved CCS. H0: Proportion of LV MSP Group subjects with Improved CCS from 6 Month Visit through 12 Month Visit ≤ 5%
	Type of Statistical Test	Other
	Comments	Even though fewer subjects (78) were available for the effectiveness endpoint analysis than originally planned (110), the study was still powered at approximately 90%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	51.3
	Confidence Interval	(1-Sided) 95%; 41.1 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event data were collected from enrollment until the time the subject's participation ended. Subjects were considered to have completed the study after 12 months of follow up.
Adverse Event Reporting Description	Reportable adverse events included the following; All Serious Adverse Events, All Heart Failure and Cardiac related Adverse Events requiring IV or invasive therapy, including new onset of cardiac events, or worsening in severity or frequency of preexisting condition, All Adverse Device Effects, All Device Deficiencies, All Adverse Events relate to the protocol required testing, excluding PNS during lead testing ad Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects.
Arm/Group Title	Single Arm
Arm/Group Description	General population who receive a Boston Scientific Resonate family of CRT-D device in accordance with its labeled indication for use.
All Cause Mortality
	Single Arm
	Affected / at Risk (%)	# Events
Total	19/584 (3.3%)
Serious Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	131/584 (22.4%)
Blood and lymphatic system disorders
Hematological	2/584 (0.3%)	2
Cardiac disorders
Atrial Fibrillation (AF)	4/584 (0.7%)	5
Atrial Tachycardia/Other SVT (eg AVRT, AVNRT, EAT)	4/584 (0.7%)	4
Cardiac arrest	2/584 (0.3%)	2
Cardiogenic shock	3/584 (0.5%)	4
Chest pain - Heart failure	2/584 (0.3%)	2
Dyspnea - Heart failure	15/584 (2.6%)	22
Gastrointestinal - Heart failure	1/584 (0.2%)	1
Incessant VT/VT Storm	1/584 (0.2%)	1
Mitral regurgitation	2/584 (0.3%)	2
Multi-system failure - Heart failure	1/584 (0.2%)	1
Multiple Ventricular Arrhythmias	1/584 (0.2%)	1
Multiple heart failure symptoms	22/584 (3.8%)	28
Other - Heart failure patient condition- Cardiovascular	4/584 (0.7%)	4
Other - Patient condition - Cardiovascular	1/584 (0.2%)	2
Palpitations	1/584 (0.2%)	1
Pericardial effusion - Unrelated (non study) procedure or device	1/584 (0.2%)	1
Pulmonary edema - Heart failure	3/584 (0.5%)	3
Renal insufficiency/failure - Heart failure	1/584 (0.2%)	1
Valvular damage/Valvular insufficiency	2/584 (0.3%)	2
Ventricular Fibrillation (VF)	1/584 (0.2%)	1
Ventricular Tachycardia (VT)/Monomorphic VT	8/584 (1.4%)	8
Weight gain - Heart failure	2/584 (0.3%)	2
Atrial (Type 1) Flutter	1/584 (0.2%)	1
Endocrine disorders
Endocrine	1/584 (0.2%)	1
Eye disorders
Heart failure symptoms - Unspecified	8/584 (1.4%)	10
Gastrointestinal disorders
Gastrointestinal	12/584 (2.1%)	13
General disorders
Chest Pain - Other	5/584 (0.9%)	7
Death	2/584 (0.3%)	2
Fatigue and Weakness	3/584 (0.5%)	3
HEENT	2/584 (0.3%)	2
Multi-System Failure	2/584 (0.3%)	2
Other-Patient Condition-Non-Cardiovascular	1/584 (0.2%)	1
Physical Trauma	3/584 (0.5%)	3
Syncope	4/584 (0.7%)	4
Infections and infestations
Fever and/or Virus	1/584 (0.2%)	1
Infection (>30 days post-implant) - PG System - Subject related	4/584 (0.7%)	4
Localized Infection	2/584 (0.3%)	2
Systemic Infection	4/584 (0.7%)	4
Injury, poisoning and procedural complications
Hematoma - Pocket (<=30 days post-implant)	3/584 (0.5%)	3
Post-surgical infection (<=30 days post-implant)	2/584 (0.3%)	2
Seroma - Pocket (<=30 days post-implant)	1/584 (0.2%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal	3/584 (0.5%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer	5/584 (0.9%)	5
Nervous system disorders
Neurological	4/584 (0.7%)	5
Product Issues
Dislodgement - LV	2/584 (0.3%)	2
Dislodgement - RA	3/584 (0.5%)	4
Dislodgement - RV	2/584 (0.3%)	2
Erosion - PG System - Subject related	1/584 (0.2%)	1
Inappropriate Tachy Therapy - SVT - PG System Therapy	1/584 (0.2%)	1
Inappropriate tachy therapy - SVT - Defibrillation lead	3/584 (0.5%)	4
Renal and urinary disorders
Genitourinary	7/584 (1.2%)	8
Renal	14/584 (2.4%)	16
Respiratory, thoracic and mediastinal disorders
COPD exacerbation	4/584 (0.7%)	4
Dyspnea	1/584 (0.2%)	1
Pulmonary	10/584 (1.7%)	11
Skin and subcutaneous tissue disorders
Integumentary	1/584 (0.2%)	1
Vascular disorders
Cerebrovascular Accident (CVA) - unspecifed	2/584 (0.3%)	2
Coronary Artery Disease	3/584 (0.5%)	3
Hematoma - Unrelated (non study) procedure or device	1/584 (0.2%)	1
Hypotension/Orthostatic Hypotension	1/584 (0.2%)	1
Myocardial Infacrtion	5/584 (0.9%)	5
Pseudoaneurysm with hematoma	1/584 (0.2%)	1
Pulmonary Embolism	2/584 (0.3%)	2
Other (Not Including Serious) Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	72/584 (12.3%)
Cardiac disorders
Premature Atrial Contraction (PAC)	1/584 (0.2%)	1
Premature Ventricular Contractions (PVC)	1/584 (0.2%)	1
Sinus tachycardia	1/584 (0.2%)	1
Ventricular Fibrillation (VF)	1/584 (0.2%)	1
Ventricular Tachycardia (VT)/Monomorphic VT	2/584 (0.3%)	3
Weight gain - Heart failure	1/584 (0.2%)	1
Gastrointestinal disorders
Gastrointestinal	2/584 (0.3%)	2
General disorders
Abnormal laboratory values	1/584 (0.2%)	2
Adverse reaction - Medication	1/584 (0.2%)	1
Chest pain - Other	1/584 (0.2%)	1
Dizziness	1/584 (0.2%)	1
Head, eyes, ears, nose, throat (HEENT)	1/584 (0.2%)	1
Multiple symptoms	1/584 (0.2%)	1
Other - Patient condition- Non-cardiovascular	1/584 (0.2%)	1
Physical trauma	1/584 (0.2%)	1
Infections and infestations
Localized Infection	1/584 (0.2%)	1
Injury, poisoning and procedural complications
Hematoma - Pocket (<=30 days post-implant)	2/584 (0.3%)	2
Post-surgical infection (<=30 days post-implant)	2/584 (0.3%)	2
Post-surgical wound discomfort/bruising/swelling	2/584 (0.3%)	2
Thromboembolic events	1/584 (0.2%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal	3/584 (0.5%)	3
Product Issues
Dislodgment - RA	1/584 (0.2%)	1
Elevated threshold - LV Lead	3/584 (0.5%)	3
Extracardiac stimulation - LV Lead	21/584 (3.6%)	22
Extracardiac stimulation - RV Lead	1/584 (0.2%)	1
Inappropriate tachy therapy - NSR -Defibrillation lead	1/584 (0.2%)	1
Inappropriate tachy therapy - SVT - Defibrillation lead	1/584 (0.2%)	1
Pacemaker Mediated Tachycardia - PG System Therapy	8/584 (1.4%)	8
Renal and urinary disorders
Genitourinary	1/584 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary	2/584 (0.3%)	2
Skin and subcutaneous tissue disorders
Integumentary	1/584 (0.2%)	1
Vascular disorders
Arterial/venous thrombolytic event	1/584 (0.2%)	1
Chest pain - Ischemic	1/584 (0.2%)	1
Hypotension/Orthostatic Hypotension	1/584 (0.2%)	1
Peripheral vascular disease	1/584 (0.2%)	1

Limitations/Caveats

Because the study was not designed to randomize subjects to conventional CRT or LV MSP, the potential incremental benefit of LV MSP cannot be quantified.

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.