InSync Model 8040 (InSync) and InSync III Model 8042 (InSync III) Registry

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00273182
• Collaborator: (none)
• Enrollment: 1,999
• Locations: 82
• Duration (Months): 109
• Patients Per Site: 24.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Heart failure is a progressive disease that decreases the pumping action of the heart. This may cause a backup of fluid in the heart and may result in heart beat changes.

When there are changes in the heart beat sometimes an implantable heart device is used to control the rate and rhythm of the heart beat. In certain heart failure cases, when the two lower chambers of the heart no longer beat in a coordinated manner, cardiac resynchronization therapy (CRT) may be prescribed. CRT is similar to a pacemaker. It is placed (implanted) under the skin of the upper chest. CRT is delivered as tiny electrical pulses to the right and left ventricles through three or four leads (soft insulated wires) that are inserted through the veins to the heart.

The purpose of this study is to monitor the long-term performance of the InSync Model 8040 (InSync) and InSync III Model 8042 (InSync III) systems for cardiac resynchronization therapy (CRT).

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; Cardiomyopathy	Device: InSync Model 8040; Device: InSync III Model 8042

Detailed Description

Condition of Approval study for cardiac resynchronization therapy with pacemakers, and for the Attain left ventricular leads 2187, 2188, 4193, and 4194.

Study Design

• Study Type: Observational
• Actual Enrollment: 1999 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: InSync Model 8040 (InSync) and InSync III Model 8042 (InSync III) Systems for Cardiac Resynchronization Therapy (CRT) - InSync Registry
• Study Start Date: Mar 1, 2002
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Cohort Patients implanted with InSync Model 8040, InSync III Model 8042 , or Medtronic CRT-D system. A total of 1999 subjects were enrolled in the study. Of them, 1738 had successful post market implants of InSync Model 8040 (601 subjects), InSync III Model 8042 (512 subjects) and CRT-D devices (625 subjects). The rest 262 subjects came from two pre-market studies: the MIRACLE study added 141 subjects to InSync Model 8040, and the InSync III study added 121 subjects to the InSync III Model 8042. A total of 1014 subjects completed the study through 36 month follow up. Follow-up of 1000 subjects was required by the FDA to satisfy the conditions of approval.

Device: InSync Model 8040; Subjects with sucessful implants of InSync Model 8040.; Device: InSync III Model 8042; Subjects with successful implants of InSync III Model 8042

Outcome Measures

Primary Outcome Measures

1. Overall Death Rate and Cause Specific Death Rate During Three Years Post Implant. [36 month follow-up]

   Survival curves of overall mortality and cause specific mortality (due to progressive heart failure and sudden cardiac death) were created based on Kaplan-Meier estimates. Estimates went out to 36 month time point. Confidence intervals were calculated on a log-log scale. The Kaplan-Meier estimates are reported in the statistical analysis modules

Secondary Outcome Measures

1. Left Ventricular (LV) Lead R-wave Amplitude [36 month follow-up]

   Summary statistics such as mean and 95% CI for the LV lead R-wave amplitude during the 36 months of follow-up.

2. Left Ventricular (LV) Lead Impedance [36 months follow-up]

   Summary statistics such as mean and 95% CI for the LV lead impedance during the 36 months of follow-up.

3. Left Ventricular (LV) Lead Pacing Voltage Threshold [36 months follow-up]

   Summary statistics such as mean and 95% CI for the LV lead pacing voltage threshold during the 36 months of follow-up

4. Subjects With Left Ventricular (LV) Lead Related Complications During Three Years Post-implant [36 months follow-up]

   A left ventricular lead related complication is defined as an adverse event that requires invasive intervention or leads to loss of significant device function resulting from the presence or performance of the LV lead. Kaplan-Meier method was used to estimate complication-free rate during the three years of follow-up. Time to the first post-implant LV lead related complication was used for the calculation. Confidence intervals were calculated on a log-log scale.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients implanted with an InSync Model 8040 or InSync III Model 8042, a right ventricular lead, and a Medtronic market-released left ventricular lead as part of a system to deliver cardiac resynchronization therapy.

Exclusion Criteria:

• Patients with a history of a previously failed placement of a currently investigational Medtronic left ventricular lead within 30 days of enrollment in the InSync Registry

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Peoria	Arizona	United States
3		Ft. Smith	Arkansas	United States
4		Little Rock	Arkansas	United States
5		Long Beach	California	United States
6		Napa	California	United States
7		Oxnard	California	United States
8		San Diego	California	United States
9		Yuba City	California	United States
10		Washington D.C.	District of Columbia	United States
11		Gainesville	Florida	United States
12		Jacksonville	Florida	United States
13		Jupiter	Florida	United States
14		Melbourne	Florida	United States
15		Miami	Florida	United States
16		Orlando	Florida	United States
17		Tampa	Florida	United States
18		Atlanta	Georgia	United States
19		Rockford	Illinois	United States
20		Springfield	Illinois	United States
21		Indianapolis	Indiana	United States
22		Des Moines	Iowa	United States
23		Kansas City	Kansas	United States
24		Overland Park	Kansas	United States
25		Lexington	Kentucky	United States
26		Louisville	Kentucky	United States
27		Lake Charles	Louisiana	United States
28		Shreveport	Louisiana	United States
29		Baltimore	Maryland	United States
30		Salisbury	Maryland	United States
31		Silver Spring	Maryland	United States
32		Boston	Massachusetts	United States
33		Worchester	Massachusetts	United States
34		Detroit	Michigan	United States
35		Kalamazoo	Michigan	United States
36		Lansing	Michigan	United States
37		Marquette	Michigan	United States
38		Saginaw	Michigan	United States
39		Duluth	Minnesota	United States
40		Minneapolis	Minnesota	United States
41		Hattiesburg	Mississippi	United States
42		Tupelo	Mississippi	United States
43		Columbia	Missouri	United States
44		Kansas City	Missouri	United States
45		Springfield	Missouri	United States
46		St. Joseph	Missouri	United States
47		St. Louis	Missouri	United States
48		Billings	Montana	United States
49		Lincoln	Nebraska	United States
50		Newark	New Jersey	United States
51		Manhasset	New York	United States
52		New York	New York	United States
53		Rochester	New York	United States
54		Chapel Hill	North Carolina	United States
55		Charlotte	North Carolina	United States
56		High Pointe	North Carolina	United States
57		Raleigh	North Carolina	United States
58		Winston-Salem	North Carolina	United States
59		Cincinnati	Ohio	United States
60		Cleveland	Ohio	United States
61		Columbus	Ohio	United States
62		Mayfield Heights	Ohio	United States
63		Oklahoma City	Oklahoma	United States
64		Doylestown	Pennsylvania	United States
65		Erie	Pennsylvania	United States
66		Philadelphia	Pennsylvania	United States
67		York	Pennsylvania	United States
68		Providence	Rhode Island	United States
69		Greenville	South Carolina	United States
70		Spartanburg	South Carolina	United States
71		Nashville	Tennessee	United States
72		Dallas	Texas	United States
73		Ft. Worth	Texas	United States
74		Houston	Texas	United States
75		Lubbock	Texas	United States
76		Sherman	Texas	United States
77		Salt Lake City	Utah	United States
78		Richmond	Virginia	United States
79		Virginia Beach	Virginia	United States
80		Seattle	Washington	United States
81		Morgantown	West Virginia	United States
82		Milwaukee	Wisconsin	United States

Sponsors and Collaborators

• Medtronic Cardiac Rhythm and Heart Failure

Investigators

• Study Chair: InSync Registry Study Leader, Medtronic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medtronic Cardiac Rhythm and Heart Failure
• ClinicalTrials.gov Identifier: NCT00273182
• Other Study ID Numbers: 187
• First Posted: Jan 9, 2006
• Last Update Posted: Aug 5, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Medtronic Cardiac Rhythm and Heart Failure: Heart Failure; Cardiomyopathy; Cardiac pacing; Cardiac resynchronization therapy
• Additional relevant MeSH terms: Heart Failure; Cardiomyopathies

Study Results

Participant Flow

Recruitment Details	The InSync Registry commenced subject enrollment on February 27, 2002. A total of 1999 subjects were enrolled in the study during the time period of February 2002 through February 2008. 1014 subjects completed the study through 36 month follow up. Follow-up of 1000 subjects was required by the FDA to satisfy the conditions of approval.
Pre-assignment Detail	1999 subjects were enrolled in the study. Of them 1738 had successful post market implants of InSync Model 8040 (n=601), InSync III Model 8042 (n=512) and CRT-D devices (n=625). The rest 262 subjects came from two pre-market studies: MIRACLE study added 141 subjects to InSync Model 8040, InSync III study added 121 to InSync III Model 8042.

Arm/Group Title	All Subjects
Arm/Group Description	Patients successfully implanted with InSync Model 8040 (including post-market new implants of InSync Model 8040 and pre-market implants from the MIRACLE study), InSync III Model 8042 (including post-market new implants of InSync III Model 8042 and pre-market implants from the InSync III study), and post-market Medtronic CRT-D devices.
Period Title: Overall Study
STARTED	1999
COMPLETED	1014
NOT COMPLETED	985

Baseline Characteristics

Arm/Group Title	All Subjects
Arm/Group Description	Patients implanted with InSync Model 8040 (including post-market new implants of InSync Model 8040 and pre-market implants from the MIRACLE study), InSync III Model 8042 (including post-market new implants of InSync III Model 8042 and pre-market implants from the InSync III study), and post-market Medtronic CRT-D devices.
Overall Participants	1999
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	686 34.3%
>=65 years	1313 65.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.2 (12.7)
Sex: Female, Male (Count of Participants)
Female	728 36.4%
Male	1271 63.6%
Region of Enrollment (participants) [Number]
United States	1999 100%

Outcome Measures

1. Primary Outcome

Title	Overall Death Rate and Cause Specific Death Rate During Three Years Post Implant.
Description	Survival curves of overall mortality and cause specific mortality (due to progressive heart failure and sudden cardiac death) were created based on Kaplan-Meier estimates. Estimates went out to 36 month time point. Confidence intervals were calculated on a log-log scale. The Kaplan-Meier estimates are reported in the statistical analysis modules
Time Frame	36 month follow-up

Outcome Measure Data

Analysis Population Description

The analysis included data from all subjects enrolled in the InSync Registry study and successfully implanted with the InSync or InSync III system.

Arm/Group Title	All Subjects
Arm/Group Description	Patients successfully implanted with InSync Model 8040 (including post-market new implants of InSync Model 8040 and pre-market implants from the MIRACLE study), InSync III Model 8042 (including post-market new implants of InSync III Model 8042 and pre-market implants from the InSync III study), and post-market Medtronic CRT-D devices.
Measure Participants	1999
Overall Death	450 22.5%
Cause Specific Death	213 10.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Subjects
	Comments	For overall mortality, the endpoint is the proportion of subjects alive during three years post-implant. Survival curves of overall mortality and cause-specific mortality were created based on Kaplan-Meier (product limit) estimates. Confidence intervals will be calculated on a log-log scale.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Overall survival rate at 36 month
	Estimated Value	71.0
	Confidence Interval	(2-Sided) 95%; 68.6 to 73.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimate is the overall survival rate at 36 month. left-truncation methods were used in the survival analysis for previously implanted subjects.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	All Subjects
	Comments	For cause-specific mortality, the endpoint is the proportion of patients who are alive or do not die due to the progressive heart failure or sudden cardiac death causes during 3 years post-implant. Survival curves of cause-specific mortality were created based on Kaplan-Meier (product limit) estimates. Confidence intervals were calculated on a log-log scale.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cause specific survival rate at 36 month
	Estimated Value	85.3
	Confidence Interval	(2-Sided) 95%; 83.3 to 87.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	left-truncation methods were used in the survival analysis for previously implanted subjects.

2. Secondary Outcome

Title	Left Ventricular (LV) Lead R-wave Amplitude
Description	Summary statistics such as mean and 95% CI for the LV lead R-wave amplitude during the 36 months of follow-up.
Time Frame	36 month follow-up

Outcome Measure Data

Analysis Population Description

1999 subjects successfully implanted with a left ventricular lead as part of a Medtronic CRT/CRT-D system.

Arm/Group Title	All Subjects
Arm/Group Description	Patients successfully implanted with InSync Model 8040 (including post-market new implants of InSync Model 8040 and pre-market implants from the MIRACLE study), InSync III Model 8042 (including post-market new implants of InSync III Model 8042 and pre-market implants from the InSync III study), and post-market Medtronic CRT-D devices.
Measure Participants	1999
6 months follow-up	13.7
12 months follow-up	13.3
18 months follow-up	13.2
24 months follow-up	13.2
30 months follow-up	13.4
36 months follow-up	13.6

3. Secondary Outcome

Title	Left Ventricular (LV) Lead Impedance
Description	Summary statistics such as mean and 95% CI for the LV lead impedance during the 36 months of follow-up.
Time Frame	36 months follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Subjects
Arm/Group Description	Patients implanted with InSync Model 8040 (including post-market new implants of InSync Model 8040 and pre-market implants from the MIRACLE study), InSync III Model 8042 (including post-market new implants of InSync III Model 8042 and pre-market implants from the InSync III study), and post-market Medtronic CRT-D devices.
Measure Participants	1999
6 months follow-up	620
12 months follow-up	625
18 months follow-up	628
24 months follow-up	622
30 months follow-up	632
36 months follow-up	633

4. Secondary Outcome

Title	Left Ventricular (LV) Lead Pacing Voltage Threshold
Description	Summary statistics such as mean and 95% CI for the LV lead pacing voltage threshold during the 36 months of follow-up
Time Frame	36 months follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Subjects
Arm/Group Description	Patients implanted with InSync Model 8040 (including post-market new implants of InSync Model 8040 and pre-market implants from the MIRACLE study), InSync III Model 8042 (including post-market new implants of InSync III Model 8042 and pre-market implants from the InSync III study), and post-market Medtronic CRT-D devices.
Measure Participants	1999
6 months follow-up	1.70
12 months follow-up	1.65
18 months follow-up	1.69
24 months follow-up	1.72
30 months follow-up	1.76
36 months follow-up	1.76

5. Secondary Outcome

Title	Subjects With Left Ventricular (LV) Lead Related Complications During Three Years Post-implant
Description	A left ventricular lead related complication is defined as an adverse event that requires invasive intervention or leads to loss of significant device function resulting from the presence or performance of the LV lead. Kaplan-Meier method was used to estimate complication-free rate during the three years of follow-up. Time to the first post-implant LV lead related complication was used for the calculation. Confidence intervals were calculated on a log-log scale.
Time Frame	36 months follow-up

Outcome Measure Data

Analysis Population Description

The analysis included data from all subjects enrolled in the InSync Registry study.

Arm/Group Title	All Subjects
Arm/Group Description	Patients successfully implanted with InSync Model 8040 (including post-market new implants of InSync Model 8040 and pre-market implants from the MIRACLE study), InSync III Model 8042 (including post-market new implants of InSync III Model 8042 and pre-market implants from the InSync III study), and post-market Medtronic CRT-D devices.
Measure Participants	1999
Number [participants]	176 8.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Subjects
	Comments	Kaplan-Meier (product limit) estimate of the curve representing the time to first post-implant LV lead related complication were calculated to the first time point where fewer than 50 patients are still at risk. Confidence intervals will be calculated on a log-log scale.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	event free rate
	Estimated Value	89.8
	Confidence Interval	(2-Sided) 95%; 88.3 to 91.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	36 months
Arm/Group Title	All Patients
Arm/Group Description	The analysis included data from all subjects enrolled in the InSync Registry study.
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	450/1999 (22.5%)
General disorders
Death	450/1999 (22.5%)	450
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	175/1999 (8.8%)
General disorders
4194 lv lead explanted	1/1999 (0.1%)	1
Elevated pacing thresholds	18/1999 (0.9%)	18
Exit block	1/1999 (0.1%)	1
Failure to capture, loss of capture	40/1999 (2%)	41
Heart failure decompensation	1/1999 (0.1%)	1
Hypotension	1/1999 (0.1%)	1
Lead conductor fracture	2/1999 (0.1%)	2
Lead dislodgment	70/1999 (3.5%)	75
Lead insulation failure	1/1999 (0.1%)	1
Muscle stimulation-diaphragm	47/1999 (2.4%)	49
Other (IPG code)	1/1999 (0.1%)	1
Oversensing	1/1999 (0.1%)	1
Pacemaker mediated tachycardia	1/1999 (0.1%)	1
Pocket erosion	1/1999 (0.1%)	1
Suboptimal position of 4194 lead	1/1999 (0.1%)	1
Unable to defibrillate	1/1999 (0.1%)	1
Undersensing	2/1999 (0.1%)	2
Ventricular fibrillation	1/1999 (0.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

In most cases, contracts allow investigators ("PI") to publish per the publication strategy/Clinical Investigation Plan following Medtronic's review for (a) disclosure of confidential information ("CI"), and (b) selection and order of publications by the publications committee. Any such CI is deleted prior to publication/presentation. Medtronic may not otherwise censor/interfere with the publication. PI's may not publish single-site data until the main multi-site publication has occurred.