Centurion: TYRX™ Envelope for Prevention of Infection Following Replacement With a CRT or ICD

• Sponsor: TYRX, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01043705
• Collaborator: (none)
• Enrollment: 1,262
• Locations: 52
• Duration (Months): 63.9
• Patients Per Site: 24.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the incidence of cardiac implantable electronic device (CIED) infection and CIED mechanical complication after CIED replacement with a high-power cardiac implantable electronic device; either a cardiac resynchronization therapy device (CRT), or an implantable cardioverter defibrilator (ICD) and TYRX Anti-Bacterial Envelope (formerly known as "AIGISRx"), to the incidence, after replacement with an ICD or CRT and no TYRX.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Implantable Electronic Device Infection

Detailed Description

Cardiac implantable electronic device (CIED) infection is associated with significant morbidity and expense. The frequency of CIED infection is increasing faster than the frequency of CIED implants, suggesting more effective prophylactic strategies are needed.

The TYRX Anti-Bacterial Envelope is an FDA-cleared polypropylene mesh that is intended to securely hold a pacemaker pulse generator or defibrillator (ICD) in order to create a stable environment when implanted in the body. It contains the antimicrobial agents, rifampin and minocycline, which have been shown to reduce infection in an in vivo model of bacterial contamination following surgical implant of the generator or defibrillator.

This is a prospective, observational, multicenter registry of subjects undergoing CIED replacement with an ICD or CRT and TYRX, with or without lead revision/addition. The registry subjects will be compared to a published historical control group undergoing CIED replacement with an ICD or CRT and no TYRX , with or without lead revision/addition. The CRT registry subjects will also be compared to a case-matched retrospective control group undergoing CIED replacement with a CRT and no TYRX , with or without lead revision/addition. The primary study endpoints are major CIED infection and CIED mechanical complication during the 12 months following CIED replacement with an ICD or CRT.

Originally executed as two separate studies (Citadel - ICDs) and (Centurion - CRTs), a protocol amendment was executed in 2012 due to slow enrollment, combining the databases for analysis of results.

Study Design

• Study Type: Observational
• Actual Enrollment: 1262 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Centurion and Citadel Studies of TYRX™ Anti-Bacterial Envelope and Custom Mesh for Prevention of Infection Following CIED Replacement With a CRT or ICD
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
CIED replacement with CRT and TYRX (Prospective Arm) Patients who have undergone CIED replacement with a CRT and the TYRX Anti-bacterial envelope, with or without lead revision.
CIED replacement with ICD and TYRX (Prospective Arm) Patients who have undergone CIED replacement with an ICD and the TYRX Anti-bacterial envelope, with or without lead revision.
CIED replacement with ICD or CRT and TYRX (Prospective Arm) Patients who have undergone CIED replacement with an ICD or CRT and the TYRX Anti-bacterial envelope, with or without lead revision.
CIED replacement w/ CRT & no TYRX (Retrospective Case-Control Arm) Patients who have undergone CIED replacement with a CRT and no TYRX Anti-bacterial envelope, with or without lead revision/addition.
CIED replacement w/ CRT & TYRX vs. Case Match Arm Patients who have undergone CIED replacement with a CRT and TYRX Anti-bacterial envelope, with or without lead revision/addition. Cohort is TYRX Case, Matched to Retrospective Case-Control Arm)

Outcome Measures

Primary Outcome Measures

1. Major CIED Infection [12 months]

   CIED Major Infections

2. CIED Mechanical Complication [12 months]

   All mechanical Complications related to CIED Implant

Eligibility Criteria

Criteria

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

Inclusion Criteria: - Prospective Arms

• Qualifying CIED Implant procedure was replacement with an ICD or CRT and TYRX, with or without lead revision/addition

• Received a complete TYRX Anti-Bacterial Envelope Model# 3122 or #3133 according to the Instructions for Use (IFU)

• Clinically stable to tolerate procedure

• 18 years or older

• Able to return for follow-up care through the 12-month visit, or able to have referring physician provide follow-up data to study site by telephone

Exclusion Criteria: - Prospective Arm

• Unable/unwilling to provide informed consent

• Contraindication to receiving the TYRX device, in accordance with the package labeling

• Pregnant or was at risk for becoming pregnant in the 30 day period following the Qualifying TYRX Implant

• Current CIED infection, or the indication for Qualifying CIED Implant was replacement of CIED that was explanted for infection

• Clinical diagnosis of an active infection at the time of CIED implant, including pneumonia, urinary tract infection, endovascular, cellulitis, bacteremia, or other major systemic infection. (Note: asymptomatic bacteremia without UTI is not an exclusion criterion)

• Generator replacement required planned lead extraction

• Participating in another clinical study evaluating a drug or device designed to reduce CIED infections

• Life expectancy of less than 6 months

• Expected to receive a heart transplant within 6 months

• With the exception of the elderly in good mental health, all vulnerable subjects as defined by the FDA Office of Human Research Protection or local IRB will be excluded

Inclusion Criteria: - Case-matched retrospective Control Arm

• Qualifying CIED Implant was replacement with a CRT and TYRX, with or without lead revision/addition

• First un-enrolled patient meeting case-matching criteria in series of patients implanted with a CIED and no TYRX beginning 24 months prior to the date of first TYRX implant at site. If no matching patients in this period, first un-enrolled matching patient implanted with a CIED and no TYRX beginning 24 months prior to the first TYRX implant at site, searching in reverse chronological order

• Had at least one of following by date of enrollment into the study:

1. ≥ 12 months follow-up after Qualifying TYRX Implant

2. Subsequent TYRX Procedure that required opening the generator pocket or implant incision ≤ 12 months after Qualifying TYRX Implant (e.g. battery change, upgrade, lead revision, explant)

3. Death ≤ 12 months after Qualifying CIED Implant

• Survived Qualifying CIED Implant to discharge, died of a CIED infection or Mechanical Complication prior to hospital discharge, or died for any reason un-related to Qualifying CIED Implant prior to hospital discharge

• 18 years or older

Exclusion Criteria: - Case-matched retrospective Control Arm

• Contraindication to receiving the TYRX device, in accordance with the package labeling

• Pregnant or became pregnant in the 30 day period following the Qualifying TYRX Implant.

• CIED infection, or the indication for Qualifying CIED Implant was replacement of CIED that was explanted for infection

• Clinical diagnosis of an active infection at the time of Qualifying CIED Implant, including pneumonia, urinary tract infection, endovascular, cellulitis, bacteremia, or other major systemic infection (Note: asymptomatic bacteriuria without UTI is not an exclusion criterion)

• Lead extraction was performed at the Qualifying CIED Implant

• Participated in another clinical study evaluating a drug or device intended to reduce CIED infections

• Received a heart transplant within 6 months of Qualifying CIED Implant

• With the exception of the elderly in good mental health, all vulnerable subjects as defined by the FDA Office of Human Research Protection or local IRB will be excluded

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Princeton Medical Center	Birmingham	Alabama	United States	35211
2	Decatur General Hospital	Decatur	Alabama	United States	35601
3	Eliza Coffee Memorial Hospital	Florence	Alabama	United States	35630
4	Riverview Regional Hospital	Gadsden	Alabama	United States	35901
5	Arizona Heart Hospital	Scottsdate	Arizona	United States	85251
6	Community Memorial Hospital	Ventura	California	United States	93003
7	Watsonville Community Hospital	Watsonville	California	United States	95076
8	Citrus Memorial Hospital	Inverness	Florida	United States	34452
9	Osceola Regional Medical Center	Kissimmee	Florida	United States	34741
10	University of Miami	Miami	Florida	United States	33136
11	Orlando Regional Hospital	Orlando	Florida	United States	32806
12	Tallahassee Memorial Hospital	Tallahassee	Florida	United States	32308
13	Piedmont Medical Center	Atlanta	Georgia	United States	30309
14	Emory University Hospital	Atlanta	Georgia	United States	30322
15	Veteran's Administration Medical Center	Atlanta	Georgia	United States	30345
16	Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
17	Trinity Medical Center	Rock Island	Illinois	United States	61201
18	St. John's Hospital	Springfield,	Illinois	United States	62769
19	St. Mary's Medical	Hobart	Indiana	United States	46342
20	Community Hospital, Munster	Munster	Indiana	United States	46321
21	St. Margaret Mercy	Munster	Indiana	United States	46321
22	P and S Surgical Hospital	Monroe	Louisiana	United States	71201
23	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
24	Johns Hopkins University Hospital	Baltimore	Maryland	United States	21205
25	Penninsula Regional Medical Center	Salisbury	Maryland	United States	21804
26	Massachusetts General Hospital	Boston	Massachusetts	United States	02144
27	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
28	Henry Ford Health System	Detroit	Michigan	United States	48202
29	Sparrow Hospital	Lansing	Michigan	United States	48910
30	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
31	Gulfport Memorial Hospital	Biloxi	Mississippi	United States	39532
32	Keesler Air Force Base Hospital	Biloxi	Mississippi	United States	39534
33	Southern Heart Center	Hattiesburg	Mississippi	United States	39401
34	Alegent Health	Omaha	Nebraska	United States	68124
35	Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
36	St. Francis Hospital	Hamilton	New Jersey	United States	08690
37	Newark Beth Israel Hospital	Newark	New Jersey	United States	07112
38	Valley Hospital	Ridgewood	New Jersey	United States	07450
39	Our Lady of Lourdes Hospital	Sewell	New Jersey	United States	08080
40	St. Luke's - Roosevelt Hospital	New York	New York	United States	10025
41	Frye Regional Medical Center	Hickory	North Carolina	United States	28601
42	Catholic Health Partners	Youngstown	Ohio	United States	44510
43	Doylestown Hospital	Doylestown	Pennsylvania	United States	18901
44	Pinnacle Health Harrisburg Hospital	Harrisburg	Pennsylvania	United States	17110
45	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
46	York Hospital	York	Pennsylvania	United States	17403
47	Landmark Medical Center	Woonsocket	Rhode Island	United States	02895
48	Stern Cardiovascular Foundation	Germantown	Tennessee	United States	38138
49	University of Tenn. Medical Center - Knoxville	Knoxville	Tennessee	United States	37920
50	Texas Heart Institute - St. Luke's Episcopal Hospital	Houston	Texas	United States	77030
51	NE Methodist	San Antonio	Texas	United States	78258
52	Aurora Health Care	Milwaukee	Wisconsin	United States	53215

Sponsors and Collaborators

• TYRX, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ballo P, Chiodi L, Zuppiroli A. Cardiac implantable electronic devices: prevention starts from ethics. Arch Intern Med. 2012 Apr 23;172(8):670-1; author reply 671-2. doi: 10.1001/archinternmed.2012.346.
• Sohail MR, Henrikson CA, Braid-Forbes MJ, Forbes KF, Lerner DJ. Comparison of mortality in women versus men with infections involving cardiovascular implantable electronic device. Am J Cardiol. 2013 Nov 1;112(9):1403-9. doi: 10.1016/j.amjcard.2013.06.031. Epub 2013 Aug 22.

• Responsible Party: TYRX, Inc.
• ClinicalTrials.gov Identifier: NCT01043705
• Other Study ID Numbers: CP-2009-2; NCT01043861
• First Posted: Jan 7, 2010
• Last Update Posted: Dec 24, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by TYRX, Inc.: Pacemaker infection; Defibrillator infection; ICD infection; CRT infection; Cardiovascular implantable electronic device infection; Infection; Pacemaker, Artificial; Defibrillators
• Additional relevant MeSH terms: Infections; Communicable Diseases

Study Results

Participant Flow

Recruitment Details	First Patient Enrolled = 1 January 2010; Last Patient Enrolled = 7 May 2013
Pre-assignment Detail	CRT and ICD Implant patients with TYRX Implant; Full analysis cohort = 1,129 patients. 670 patient CRT + TYRX cohort is subset. 459 patient ICD + TYRX is subset. 578 CRT+ TYRX patient cohort is subset matched to 578 patient CRT/no TYRX retrospective patient arm.

Arm/Group Title	ICD With TYRX Implant	CRT and TYRX Cases, Matched to Retrospective Non-TYRX Implants	CRT With no TYRX Retrospective Case Control
Arm/Group Description	All patients receiving a TYRX envelope who were eligible to participate having a replacement ICD implant	Patients receiving a TYRX envelope who were eligible to participate having a replacement CRT implant who have a valid non-TYRX implant case-match	Retrospective site matched and case-matched CRT replacement patients who did not receive a TYRX envelope selected in the era just prior to availability of TYRX Envelope
Period Title: Overall Study
STARTED	459	578	578
COMPLETED	352	447	498
NOT COMPLETED	107	131	80

Baseline Characteristics

Arm/Group Title	CIED Replacement With ICD and TYRX	CIED Replacement With CRT and no TYRX	CIED Replacement With CRT and TYRX Vs. Case Match Arm	Total
Arm/Group Description	(Prospective Arm) Patients who have undergone CIED replacement with an ICD and the TYRX Anti-bacterial envelope, with or without lead revision.	(Retrospective Case-Control Arm) Patients who have undergone CIED replacement with a CRT and no TYRX Anti-bacterial envelope, with or without lead revision/addition.	Prospective CRT patients who received a TYRX envelope and had a valid case match retrospective patient. This is a subset of all CRT/TYRX patients	Total of all reporting groups
Overall Participants	459	578	578	1615
Age (Years) [Median (Standard Deviation) ]
Median (Standard Deviation) [Years]	70 (12.01)	73 (10.94)	73 (10.70)	72 (11.45)
Sex: Female, Male (Count of Participants)
Female	339 73.9%	434 75.1%	444 76.8%	1217 75.4%
Male	120 26.1%	144 24.9%	134 23.2%	398 24.6%

Outcome Measures

1. Primary Outcome

Title	Major CIED Infection
Description	CIED Major Infections
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Evaluable patients that have valid entry criteria

Arm/Group Title	CIED Replacement With CRT and TYRX	CIED Replacement With CRT and no TYRX	CIED Replacement With CRT and TYRX vs. Case Match Arm
Arm/Group Description	(Prospective Arm) Patients who have undergone CIED replacement with a CRT and the TYRX Anti-bacterial envelope, with or without lead revision.	(Retrospective Case-Control Arm) Patients who have undergone CIED replacement with a CRT and no TYRX Anti-bacterial envelope, with or without lead revision/addition.	CIED replacement with CRT and TYRX vs. Case Match Arm; CRT patients who have corresponding non-TYRX implant case-match
Measure Participants	670	578	578
Number (95% Confidence Interval) [percentage of Participants]	0.6 0.1%	1.0 0.2%	0.7 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CIED Replacement With CRT and TYRX, CIED Replacement With CRT and no TYRX
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0023
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	One sided Fisher's exact test.
	Estimated Value	0.0044
	Confidence Interval	(1-Sided) 95%; to 0.009
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CIED Replacement With CRT and TYRX, CIED Replacement With CRT and no TYRX
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0052
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	1-sided Fisher's Exact Text
	Estimated Value	0.002
	Confidence Interval	(1-Sided) 95%; to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CIED Replacement With CRT and TYRX
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0176
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	1-sided Fisher's Exact Test
	Estimated Value	0.006
	Confidence Interval	(1-Sided) 95%; to 0.014
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CIED Replacement With CRT and no TYRX, CIED Replacement With CRT and TYRX vs. Case Match Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3764
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Fisher's Exact Test
	Estimated Value	.7
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	CIED Mechanical Complication
Description	All mechanical Complications related to CIED Implant
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

TYRX implants vs. published comparator are "prospective arm" patients. Non-TYRX CIED retrospective arm vs. TYRX CIED replacements are nested, case-control cohort.

Arm/Group Title	CIED Replacement With ICD and TYRX	CIED Replacement With CRT and no TYRX	CIED Replacement With CRT and TYRX vs. Case Match Arm
Arm/Group Description	(Prospective Arm) Patients who have undergone CIED replacement with an ICD and the TYRX Anti-bacterial envelope, with or without lead revision.	(Retrospective Case-Control Arm) Patients who have undergone CIED replacement with a CRT and no TYRX Anti-bacterial envelope, with or without lead revision/addition.	CIED replacement with CRT and TYRX vs. Case Match Arm; CRT patients who have corresponding non-TYRX implant case-match
Measure Participants	459	578	578
Number (95% Confidence Interval) [percentage of Participants]	3.1 0.7%	5.5 1%	5.4 0.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CIED Replacement With CRT and TYRX, CIED Replacement With CRT and no TYRX
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	1-sided Chi-square
	Comments
Method of Estimation	Estimation Parameter	Rate compared to performance goal
	Estimated Value	4.4
	Confidence Interval	(2-Sided) 95%; 3.3 to 5.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CIED Replacement With CRT and TYRX
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0444
	Comments
	Method	1-sided Chi-square test
	Comments
Method of Estimation	Estimation Parameter	Rate compared to a performance goal
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; 1.7 to 5.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CIED Replacement With CRT and TYRX, CIED Replacement With CRT and no TYRX
	Comments	All types of mechanical complications combined.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	1-sided Chi-squared test
	Comments
Method of Estimation	Estimation Parameter	rate compared to performance goal
	Estimated Value	5.4
	Confidence Interval	(2-Sided) 95%; 3.8 to 5.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CIED Replacement With CRT and no TYRX, CIED Replacement With CRT and TYRX vs. Case Match Arm
	Comments	All mechanical complications, retrospective, non-TYRX cohort
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0745
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Descriptive
	Estimated Value	5.4
	Confidence Interval	(2-Sided) 95%; 3.7 to 7.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	During 12 month follow up period
Adverse Event Reporting Description	Note that non-serious adverse events were not collected or assessed as part of this study. Adverse events coded as "death" do not have further description.
Arm/Group Title	CIED Replacement With CRT and TYRX		CIED Replacement With ICD and TYRX
Arm/Group Description	(Prospective Arm) Patients who have undergone CIED replacement with a CRT and the TYRX Anti-bacterial envelope, with or without lead revision.		(Prospective Arm) Patients who have undergone CIED replacement with an ICD and the TYRX Anti-bacterial envelope, with or without lead revision.
All Cause Mortality
	CIED Replacement With CRT and TYRX		CIED Replacement With ICD and TYRX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CIED Replacement With CRT and TYRX		CIED Replacement With ICD and TYRX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/578 (16.6%)		46/459 (10%)
Blood and lymphatic system disorders
Anaemia	0/578 (0%)	0	1/459 (0.2%)	1
Leukocytosis	2/578 (0.3%)	2	1/459 (0.2%)	1
Cardiac disorders
Acute Myocardial Infarction	2/578 (0.3%)	2	1/459 (0.2%)	1
Aortic Valve Stenosis	1/578 (0.2%)	1	0/459 (0%)	0
Atrial Fibrillation	2/578 (0.3%)	2	1/459 (0.2%)	1
Atrial Thrombosis	1/578 (0.2%)	1	0/459 (0%)	0
Cardiac Amyloidosis	1/578 (0.2%)	1	0/459 (0%)	0
Cardiac Arrest	5/578 (0.9%)	5	2/459 (0.4%)	2
Cardiac disorder	2/578 (0.3%)	2	0/459 (0%)	0
Cardiac Failure	1/578 (0.2%)	1	1/459 (0.2%)	1
Cardiac Failure Acute	2/578 (0.3%)	2	0/459 (0%)	0
Cardiac Failure Congestive	18/578 (3.1%)	18	6/459 (1.3%)	6
Cardio-respiratory failure	4/578 (0.7%)	4	1/459 (0.2%)	1
Cardiogenic Shock	1/578 (0.2%)	1	1/459 (0.2%)	1
Cardiomyopathy	2/578 (0.3%)	2	1/459 (0.2%)	1
Cardiopulmonary Failure	1/578 (0.2%)	1	0/459 (0%)	0
Coronary Artery Disease	3/578 (0.5%)	3	0/459 (0%)	0
Ischemic Cardiomyopathy	3/578 (0.5%)	3	0/459 (0%)	0
Low Cardiac Output Syndrome	1/578 (0.2%)	1	0/459 (0%)	0
Mitral Valve Incompetence	1/578 (0.2%)	1	0/459 (0%)	0
Myocardial Infarction	1/578 (0.2%)	1	1/459 (0.2%)	1
Palpitations	1/578 (0.2%)	1	0/459 (0%)	0
Restrictive Cardiomyopathy	1/578 (0.2%)	1	0/459 (0%)	0
Tricuspid Valve Incompetence	1/578 (0.2%)	1	0/459 (0%)	0
Ventricular Tachycardia	0/578 (0%)	0	2/459 (0.4%)	2
Endocrine disorders
Hypothyroidism	1/578 (0.2%)	1	0/459 (0%)	0
Gastrointestinal disorders
Gastrointestinal Heamorrhage	1/578 (0.2%)	1	0/459 (0%)	0
Gastrooesophageal Reflux Disease	1/578 (0.2%)	1	0/459 (0%)	0
Lower Gastrointestinal Haemorrhage	0/578 (0%)	0	1/459 (0.2%)	1
Rectal Haemorrhage	1/578 (0.2%)	1	0/459 (0%)	0
General disorders
Adverse Drug Reaction	1/578 (0.2%)	1	0/459 (0%)	0
Asthenia	2/578 (0.3%)	2	0/459 (0%)	0
Brain Death	1/578 (0.2%)	1	0/459 (0%)	0
Chest Pain	2/578 (0.3%)	2	0/459 (0%)	0
Chills	1/578 (0.2%)	1	0/459 (0%)	0
Complication of Device Removal	0/578 (0%)	0	1/459 (0.2%)	1
Condition Aggravated	1/578 (0.2%)	1	0/459 (0%)	0
Death	45/578 (7.8%)	45	24/459 (5.2%)	24
Device Component Issue	0/578 (0%)	0	1/459 (0.2%)	1
Device dislocation	4/578 (0.7%)	4	1/459 (0.2%)	1
Device Electrical Finding	0/578 (0%)	0	1/459 (0.2%)	1
Device Failure	0/578 (0%)	0	1/459 (0.2%)	1
Device Lead Damage	2/578 (0.3%)	2	1/459 (0.2%)	1
Device Lead Issue	0/578 (0%)	0	1/459 (0.2%)	1
Device Malfunction	1/578 (0.2%)	1	1/459 (0.2%)	1
Device Pacing Issue	0/578 (0%)	0	1/459 (0.2%)	1
Device Stimulation Issue	1/578 (0.2%)	1	0/459 (0%)	0
Feeling Hot	1/578 (0.2%)	1	0/459 (0%)	0
General Physical Health Deterioration	4/578 (0.7%)	4	1/459 (0.2%)	1
Impaired Healing	1/578 (0.2%)	1	0/459 (0%)	0
Implant Site Discharge	1/578 (0.2%)	1	0/459 (0%)	0
Implant Site Haematoma	6/578 (1%)	6	0/459 (0%)	0
Implant Site Haemorrhage	0/578 (0%)	0	1/459 (0.2%)	1
Implant Site Pain	0/578 (0%)	0	1/459 (0.2%)	1
Medical Device Site Reaction	1/578 (0.2%)	1	0/459 (0%)	0
Multi-Organ Failure	1/578 (0.2%)	1	0/459 (0%)	0
Multimorbidity	0/578 (0%)	0	1/459 (0.2%)	1
Oedema Peripheral	1/578 (0.2%)	1	0/459 (0%)	0
Pyrexia	2/578 (0.3%)	2	0/459 (0%)	0
Treatment Failure	1/578 (0.2%)	1	0/459 (0%)	0
Infections and infestations
Cardiac Valve Vegetation	1/578 (0.2%)	1	0/459 (0%)	0
Device Related Infection	2/578 (0.3%)	2	1/459 (0.2%)	1
Endocarditis	1/578 (0.2%)	1	0/459 (0%)	0
Implant Site Cellulitis	0/578 (0%)	0	1/459 (0.2%)	1
Implant Site Infection	2/578 (0.3%)	2	3/459 (0.7%)	3
Infected Skin Ulcer	1/578 (0.2%)	1	0/459 (0%)	0
Infection	1/578 (0.2%)	1	0/459 (0%)	0
Klebsiella Sepsis	1/578 (0.2%)	1	0/459 (0%)	0
Pneumonia	7/578 (1.2%)	7	2/459 (0.4%)	2
Pneumonia Staphylococcal	1/578 (0.2%)	1	0/459 (0%)	0
Sepsis	1/578 (0.2%)	1	2/459 (0.4%)	2
Septic Shock	1/578 (0.2%)	1	1/459 (0.2%)	1
Staphylococcal Bacteraemia	1/578 (0.2%)	1	0/459 (0%)	0
Streptococcal Sepsis	1/578 (0.2%)	1	0/459 (0%)	0
Urinary Tract Infection	0/578 (0%)	0	1/459 (0.2%)	1
Urosepsis	1/578 (0.2%)	1	0/459 (0%)	0
Injury, poisoning and procedural complications
Eschar	1/578 (0.2%)	1	0/459 (0%)	0
Fall	3/578 (0.5%)	3	1/459 (0.2%)	1
Fibula Fracture	1/578 (0.2%)	1	0/459 (0%)	0
Incision Site Haematoma	1/578 (0.2%)	1	0/459 (0%)	0
Post Procedural Discharge	1/578 (0.2%)	1	0/459 (0%)	0
Seroma	0/578 (0%)	0	1/459 (0.2%)	1
Tibia Fracture	1/578 (0.2%)	1	0/459 (0%)	0
Wound Dehiscence	2/578 (0.3%)	2	1/459 (0.2%)	1
Investigations
Blood Creatinine Increased	1/578 (0.2%)	1	1/459 (0.2%)	1
Blood Culture Positive	1/578 (0.2%)	1	0/459 (0%)	0
Blood Urea Increased	1/578 (0.2%)	1	0/459 (0%)	0
Blood Urea Nitrogen/Creatinine Ratio Increased	1/578 (0.2%)	1	0/459 (0%)	0
International Normalised Ratio Increased	1/578 (0.2%)	1	0/459 (0%)	0
Troponin Increased	0/578 (0%)	0	1/459 (0.2%)	1
Metabolism and nutrition disorders
Dehydration	1/578 (0.2%)	1	0/459 (0%)	0
Diabetes Mellitus	1/578 (0.2%)	1	0/459 (0%)	0
Failure to Thrive	1/578 (0.2%)	1	0/459 (0%)	0
Hyponatraemia	1/578 (0.2%)	1	0/459 (0%)	0
Hypovolaemia	1/578 (0.2%)	1	0/459 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/578 (0.3%)	2	1/459 (0.2%)	1
Pain in Extremity	1/578 (0.2%)	1	1/459 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgin's Disease	1/578 (0.2%)	1	0/459 (0%)	0
Lung Neoplasm Malignant	1/578 (0.2%)	1	1/459 (0.2%)	1
Lymphoma	1/578 (0.2%)	1	0/459 (0%)	0
Neoplasm Malignant	1/578 (0.2%)	1	0/459 (0%)	0
Non-Small Cell Lung Cancer Recurrent	1/578 (0.2%)	1	0/459 (0%)	0
Oesophageal Carcinoma	1/578 (0.2%)	1	0/459 (0%)	0
Nervous system disorders
Convulsion	0/578 (0%)	0	1/459 (0.2%)	1
Dementia	1/578 (0.2%)	1	0/459 (0%)	0
Ischaemic Stroke	0/578 (0%)	0	1/459 (0.2%)	1
Lethargy	2/578 (0.3%)	2	0/459 (0%)	0
Loss of Consciousness	1/578 (0.2%)	1	0/459 (0%)	0
Presyncope	1/578 (0.2%)	1	0/459 (0%)	0
Syncope	1/578 (0.2%)	1	0/459 (0%)	0
Psychiatric disorders
Anxiety	1/578 (0.2%)	1	0/459 (0%)	0
Confusional State	2/578 (0.3%)	2	0/459 (0%)	0
Renal and urinary disorders
Renal Failure	2/578 (0.3%)	2	2/459 (0.4%)	2
Renal Failure Acute	4/578 (0.7%)	4	0/459 (0%)	0
Renal Failure Chronic	1/578 (0.2%)	1	1/459 (0.2%)	1
Renal Mass	1/578 (0.2%)	1	0/459 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/578 (0.2%)	1	0/459 (0%)	0
Chronic Obstructive Pulmonary Disease	2/578 (0.3%)	2	0/459 (0%)	0
Cough	2/578 (0.3%)	2	0/459 (0%)	0
Dyspnoea	9/578 (1.6%)	9	4/459 (0.9%)	4
Hypoxia	1/578 (0.2%)	1	0/459 (0%)	0
Lung Consolidation	2/578 (0.3%)	2	0/459 (0%)	0
Long Disorder	2/578 (0.3%)	2	0/459 (0%)	0
Orthopnoea	0/578 (0%)	0	1/459 (0.2%)	1
Pleural Effusion	3/578 (0.5%)	3	0/459 (0%)	0
Productive Cough	1/578 (0.2%)	1	0/459 (0%)	0
Pulmonary Embolism	1/578 (0.2%)	1	0/459 (0%)	0
Pulmonary Mass	1/578 (0.2%)	1	0/459 (0%)	0
Pulmonary Oedema	1/578 (0.2%)	1	0/459 (0%)	0
Respiratory Failure	2/578 (0.3%)	2	1/459 (0.2%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/578 (0.2%)	1	0/459 (0%)	0
Rash	1/578 (0.2%)	1	0/459 (0%)	0
Skin Erosion	0/578 (0%)	0	1/459 (0.2%)	1
Surgical and medical procedures
Aortic Valve Replacement	1/578 (0.2%)	1	0/459 (0%)	0
Cardiac Pacemaker Removal	1/578 (0.2%)	1	0/459 (0%)	0
Cardiac Pacemaker Replacement	3/578 (0.5%)	3	1/459 (0.2%)	1
Cardio Pacemaker Revision	0/578 (0%)	0	1/459 (0.2%)	1
Cardioversion	2/578 (0.3%)	2	1/459 (0.2%)	1
Chest Tube Insertion	1/578 (0.2%)	1	0/459 (0%)	0
Drain Placement	1/578 (0.2%)	1	0/459 (0%)	0
Emergency Care	5/578 (0.9%)	5	1/459 (0.2%)	1
Endotracheal Intubation	1/578 (0.2%)	1	0/459 (0%)	0
Haemodialysis	1/578 (0.2%)	1	1/459 (0.2%)	1
Hospice Care	4/578 (0.7%)	4	0/459 (0%)	0
Hospitalisation	27/578 (4.7%)	27	10/459 (2.2%)	10
Implantable Defibrillator Insertion	0/578 (0%)	0	1/459 (0.2%)	1
Incisional Drainage	1/578 (0.2%)	1	0/459 (0%)	0
Mechanical Ventilation	1/578 (0.2%)	1	0/459 (0%)	0
Medical Device Change	1/578 (0.2%)	1	0/459 (0%)	0
Medical Device Removal	1/578 (0.2%)	1	1/459 (0.2%)	1
Packed Red Blood Cell Transfusion	1/578 (0.2%)	1	0/459 (0%)	0
Palliative Care	2/578 (0.3%)	2	3/459 (0.7%)	3
Rehabilitation Therapy	1/578 (0.2%)	1	1/459 (0.2%)	1
Tracheostomy	1/578 (0.2%)	1	0/459 (0%)	0
Ventricular Assist Device Insertion	1/578 (0.2%)	1	0/459 (0%)	0
Withdrawal of Life Support	1/578 (0.2%)	1	0/459 (0%)	0
Wound Drainage	1/578 (0.2%)	1	0/459 (0%)	0
Vascular disorders
Distributive Shock	1/578 (0.2%)	1	0/459 (0%)	0
Haematoma	0/578 (0%)	0	1/459 (0.2%)	1
Hypotension	3/578 (0.5%)	3	0/459 (0%)	0
Peripheral Arterial Occlusive Disease	1/578 (0.2%)	1	0/459 (0%)	0
Other (Not Including Serious) Adverse Events
	CIED Replacement With CRT and TYRX		CIED Replacement With ICD and TYRX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

This was a non-randomized study and did not have an active comparator.

More Information

Certain Agreements

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

There is NOT 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.