WRAP-IT: World-wide Randomized Antibiotic Envelope Infection Prevention Trial

Sponsor

Medtronic Cardiac Rhythm and Heart Failure (Industry)

Overall Status

Completed

CT.gov ID

NCT02277990

Collaborator

The Cleveland Clinic (Other)

7,075

Enrollment

181

Locations

Arms

Actual Duration (Months)

39.1

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Medtronic , Inc. is sponsoring the World-wide Randomized Antibiotic Envelope Infection Prevention Trial (WRAP-IT), a randomized, prospective, multi-center, single blinded, post-market, interventional clinical study. This study will evaluate the ability of the TYRX™ envelope to reduce major Cardiac Implantable Electronic Device (CIED) infections through 12-months post-procedure following CIED generator replacement, upgrade, revision, or de novo cardiac resynchronization therapy defibrillator (CRT-D) implant. Additionally, this large device study provides the unique opportunity to prospectively characterize the performance of Medtronic's lead monitoring features in subjects whose CIED system includes a transvenous right ventricular (RV) defibrillation lead. Finally, the WRAP-IT study will serve as a post-approval study for those geographies requiring a post-approval study of the TYRX™ envelope.

Condition or Disease	Intervention/Treatment	Phase
CIED Related Infection	Device: TYRX™ Absorbable Antibacterial Envelope	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

7075 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Prevention

Official Title:

Cardiac Implantable Electronic Device (CIED) Antibiotic Envelope Infection Prevention Trial

Actual Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

Sep 1, 2018

Actual Study Completion Date :

Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: TYRX™ envelope The Medtronic TYRX™ Absorbable Antibacterial Envelope is an absorbable sterile prosthesis designed to hold a pacemaker pulse generator or defibrillator to create a stable environment when implanted in the body. The purpose of the absorbable coating is to act as a carrier for the antimicrobial agents.	Device: TYRX™ Absorbable Antibacterial Envelope
No Intervention: Control No TYRX™ envelope, bare CIED

Arm

Intervention/Treatment

Active Comparator: TYRX™ envelope

The Medtronic TYRX™ Absorbable Antibacterial Envelope is an absorbable sterile prosthesis designed to hold a pacemaker pulse generator or defibrillator to create a stable environment when implanted in the body. The purpose of the absorbable coating is to act as a carrier for the antimicrobial agents.

Device: TYRX™ Absorbable Antibacterial Envelope

No Intervention: Control

No TYRX™ envelope, bare CIED

Outcome Measures

Primary Outcome Measures

12 Month Kaplan-Meier Estimate of Major CIED Infection Rate [Implant to 12 months]
CIED infections are defined as (1) superficial cellulitis in the region of the CIED pocket with wound dehiscence, erosion, or purulent drainage, (2) deep incisional or organ/space (generator pocket) surgical site infection that meets the Centers for Disease Control and Prevention criteria, independent from time of surgery, (3) persistent bacteremia, or (4) endocarditis. Major CIED infections are defined as a CIED infection resulting in one or more of the following: CIED system removal Any invasive procedure (e.g. pocket opened) without system removal Treatment with antibiotic therapy if the subject is not a candidate for system removal and infection recurrence after completion of antibiotic therapy or evidence of deep infection with wound dehiscence, erosion, or purulent drainage Death

Secondary Outcome Measures

12 Month Kaplan-Meier Estimate of Major or Minor CIED Infection [Implant to 12 months]
Major CIED infections are defined above. Minor CIED infections are defined as CIED infections that do not meet the definition of a major CIED infection
12 Month Kaplan-Meier Estimate of a CIED Procedure Related or System Related Complication [Implant to 12 months]
A CIED system related event is defined as an adverse event related to the CIED system which includes the device, leads, implant tool(s), programmer, or TYRX envelope (if applicable) A CIED procedure related event is defined as an adverse event that occurs due to any procedure related to the implantation or surgical modification of the system including the TYRX envelope (if applicable) A procedure or system related complication is defined as an adverse event related to a CIED procedure or the CIED system that results in at least one of the following: Death,Termination of significant device function, Invasive intervention
Kaplan-Meier Estimate of a Major Infection Throughout Follow-up [Throughout study follow-up Kaplan-Meier Estimate is at 36 Months]
CIED infections are defined as (1) superficial cellulitis in the region of the CIED pocket with wound dehiscence, erosion, or purulent drainage, (2) deep incisional or organ/space (generator pocket) surgical site infection that meets the Centers for Disease Control and Prevention criteria, independent from time of surgery, (3) persistent bacteremia, or (4) endocarditis. Major CIED infections are defined as a CIED infection resulting in one or more of the following: CIED system removal Any invasive procedure (e.g. pocket opened) without system removal Treatment with antibiotic therapy if the subject is not a candidate for system removal and infection recurrence after completion of antibiotic therapy or evidence of deep infection with wound dehiscence, erosion, or purulent drainage Death

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Patient is willing to sign and date the study patient informed consent (PIC) form
Patient is at least 18 years of age and meets age requirements per local law
Patient is planned to undergo at least one of the following:

Patient has existing cardiac implantable electronic device (CIED) and is undergoing implantable pulse generator (IPG) (including cardiac resynchronization therapy pacemaker [CRT-P]), implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) replacement or upgrade with a new Medtronic generator
Subjects planned to have leads added, or extracted and added for upgrades can be enrolled OR
Patient will undergo a de novo Medtronic CRT-D system implant per approved indications

Patient has existing study eligible Medtronic CIED in which the pocket was not accessed within the last 365 days, and is undergoing pocket or lead revision

Willing to provide the contact information for the physician who provides followup for his/her CIED
Willing and able to comply with scheduled follow-up and study related activities

Exclusion Criteria:

Known allergy to minocycline or rifampin or their derivatives, or any other known contraindications to implantation of the TYRX envelope.
Current therapy with chronic oral immunosuppressive agents or ≥ 20mg/day of Prednisone or equivalent.
Hemodialysis or peritoneal dialysis.
Prior Cardiac transplantation or existing Ventricular Assist Device (VAD).
Require long-term vascular access for any reason.
Prior history of a CIED infection, other prosthetic device infection, or endovascular infection, including endocarditis, in the past 12 months.
Physical, clinical, or laboratory signs or symptoms consistent with an active infection (including but not limited to pneumonia, urinary tract, cellulitis, or bacteremia)
Systemic lupus erythematous, because minocycline has been reported to aggravate this condition
Female patient who is pregnant, or of childbearing potential and not on a reliable form of birth control. Women of childbearing potential are required to have a negative pregnancy test within 7 days prior to device procedure
Participation in another study that may confound the results of this study. Co-enrollment in concurrent trials is only allowed when documented pre-approval is obtained from the Medtronic study manager.

Contacts and Locations

Locations

	Site	City	State	Country
1	Alaska Heart Institute	Anchorage	Alaska	United States
2	Tri-City Cardiology Consultants	Mesa	Arizona	United States
3	Arizona Arrhythmia Consultants	Scottsdale	Arizona	United States
4	Chula Vista Cardiac Center	Chula Vista	California	United States
5	Cardiovascular Consultants Heart Center	Fresno	California	United States
6	UCSD Medical Center	La Jolla	California	United States
7	Eisenhower Desert Cardiology Center	Rancho Mirage	California	United States
8	University of California San Francisco UCSF Medical Center	San Francisco	California	United States
9	Stanford Hospital & Clinics	Stanford	California	United States
10	Saint Joseph's Medical Center	Stockton	California	United States
11	Penrose St. Francis Hospital	Colorado Springs	Colorado	United States
12	Swedish Medical Center	Englewood	Colorado	United States
13	SCL Physicians Heart Institute of Colorado	Lafayette	Colorado	United States
14	Danbury Hospital	Danbury	Connecticut	United States
15	Hartford Hospital	Hartford	Connecticut	United States
16	MedStar Washington Hospital Center	Washington	District of Columbia	United States
17	Florida Electrophysiology Associates	Atlantis	Florida	United States
18	Clearwater Cardiovascular & Interventional Consultants	Clearwater	Florida	United States
19	The Cardiac & Vascular Institute	Gainesville	Florida	United States
20	University of Florida Health Shands Hospital	Gainesville	Florida	United States
21	Kootenai Heart Clinics Northwest	Coeur d'Alene	Idaho	United States
22	NorthShore University Health System	Evanston	Illinois	United States
23	Loyola University Medical Center	Maywood	Illinois	United States
24	Prairie Education & Research Cooperative (Springfield IL)	Springfield	Illinois	United States
25	Saint Vincent Medical Group	Indianapolis	Indiana	United States
26	Iowa Heart Center	West Des Moines	Iowa	United States
27	The University Kansas Medical Center Research Institute Inc	Kansas City	Kansas	United States
28	Lexington Cardiac Research Foundation	Lexington	Kentucky	United States
29	Norton Cardiovascular Associates	Louisville	Kentucky	United States
30	Cardiovascular Research Foundation of Louisiana	Baton Rouge	Louisiana	United States
31	Advanced Cardiovascular Specialists	Shreveport	Louisiana	United States
32	Maine Medical Center	Scarborough	Maine	United States
33	MedStar Health Research Institute	Baltimore	Maryland	United States
34	Sinai Hospital of Baltimore	Baltimore	Maryland	United States
35	Delmarva Heart Research Foundation Inc	Salisbury	Maryland	United States
36	Massachusetts General Hospital	Boston	Massachusetts	United States
37	University of Michigan	Ann Arbor	Michigan	United States
38	Sparrow Clinical Research Institute	Lansing	Michigan	United States
39	DLP Marquette Physicians Practices Inc	Marquette	Michigan	United States
40	Upper Michigan Cardiovascular Associates PC	Marquette	Michigan	United States
41	Beaumont Hospital - Royal Oak	Royal Oak	Michigan	United States
42	Great Lakes Heart and Vascular Institute PC	Saint Joseph	Michigan	United States
43	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota	United States
44	University of Minnesota Medical Center	Minneapolis	Minnesota	United States
45	North Memorial Heart and Vascular Institute	Robbinsdale	Minnesota	United States
46	Mayo Clinic	Rochester	Minnesota	United States
47	CentraCare Heart & Vascular Center	Saint Cloud	Minnesota	United States
48	United Heart and Vascular Clinic	Saint Paul	Minnesota	United States
49	Hattiesburg Clinic/ Forrest General	Hattiesburg	Mississippi	United States
50	Mid America Heart Institute (MAHI)	Kansas City	Missouri	United States
51	Saint Anthonys Medical Center	Saint Louis	Missouri	United States
52	Washington University School of Medicine	Saint Louis	Missouri	United States
53	Mercy Hospital Springfield	Springfield	Missouri	United States
54	University of Nebraska	Omaha	Nebraska	United States
55	Englewood Hospital & Medical Center	Englewood	New Jersey	United States
56	Jersey Shore University Medical Center	Neptune	New Jersey	United States
57	Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States
58	The Valley Hospital	Ridgewood	New Jersey	United States
59	Lourdes Cardiology Services	Voorhees	New Jersey	United States
60	Saint Joseph's Hospital Health Center	Liverpool	New York	United States
61	Cornell University Medical Center	New York	New York	United States
62	Mount Sinai Saint Luke's Hospital	New York	New York	United States
63	New York Presbyterian Hospital	New York	New York	United States
64	NYU	New York	New York	United States
65	University of Rochester Medical Center	Rochester	New York	United States
66	Westchester Medical Center	Valhalla	New York	United States
67	Asheville Cardiology Associate PA	Asheville	North Carolina	United States
68	Novant Health Heart and Vascular Institute	Charlotte	North Carolina	United States
69	Duke University Medical Center (DUMC)	Durham	North Carolina	United States
70	Raleigh Cardiology Associates	Raleigh	North Carolina	United States
71	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina	United States
72	Wake Forest University Health Sciences / Baptist Medical Center / North Carolina Baptist Hospital	Winston-Salem	North Carolina	United States
73	Akron General Medical Center	Akron	Ohio	United States
74	Northeast Ohio Cardiovascular Specialists	Akron	Ohio	United States
75	The Lindner Research Center	Cincinnati	Ohio	United States
76	Cleveland Clinic	Cleveland	Ohio	United States
77	University Hospitals Case Medical Center	Cleveland	Ohio	United States
78	OhioHealth Riverside Methodist Hospital	Columbus	Ohio	United States
79	The Ohio State University	Columbus	Ohio	United States
80	Saint Elizabeth Health Center	Poland	Ohio	United States
81	Mount Carmel East	Westerville	Ohio	United States
82	Oklahoma Heart Hospital Research Foundation	Oklahoma City	Oklahoma	United States
83	University of Oklahoma Health Science Center (OUHSC)	Oklahoma City	Oklahoma	United States
84	Oklahoma Heart Institute	Tulsa	Oklahoma	United States
85	Legacy Medical Group	Portland	Oregon	United States
86	Oregon Health & Science University Hospital	Portland	Oregon	United States
87	Providence Health & Services	Portland	Oregon	United States
88	Lehigh Valley Hospital Cedar Crest	Allentown	Pennsylvania	United States
89	Saint Luke's Hospital	Bethlehem	Pennsylvania	United States
90	Geisinger Medical Center	Danville	Pennsylvania	United States
91	Doylestown Cardiology Associates - VIAA	Doylestown	Pennsylvania	United States
92	University of Pittsburgh Medical Center UPMC Hamot	Erie	Pennsylvania	United States
93	Saint Mary Medical Center (Langhorne PA)	Newtown	Pennsylvania	United States
94	Drexel University College of Medicine	Philadelphia	Pennsylvania	United States
95	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States
96	Temple University Hospital	Philadelphia	Pennsylvania	United States
97	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States
98	University of Pennsylvania	Philadelphia	Pennsylvania	United States
99	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States
100	University of Pittsburgh Medical Center UPMC Presbyterian	Pittsburgh	Pennsylvania	United States
101	The Miriam Hospital	East Providence	Rhode Island	United States
102	The Stern Cardiovascular Foundation	Germantown	Tennessee	United States
103	Jackson Clinic	Jackson	Tennessee	United States
104	Wellmont CVA Heart Institute	Kingsport	Tennessee	United States
105	Centennial Heart Cardiovascular Consultants LLC	Nashville	Tennessee	United States
106	Saint Thomas Research Institute	Nashville	Tennessee	United States
107	Amarillo Heart Group	Amarillo	Texas	United States
108	Cardiology Associates of Corpus Christi	Corpus Christi	Texas	United States
109	Baylor Heart & Vascular Hospital	Dallas	Texas	United States
110	North Texas Heart Center	Dallas	Texas	United States
111	Plaza Medical Center of Fort Worth	Fort Worth	Texas	United States
112	Longview Regional Medical Center	Longview	Texas	United States
113	Baylor Research Institute	Plano	Texas	United States
114	Scott & White Health Science Ctr	Temple	Texas	United States
115	EP Heart LLC	The Woodlands	Texas	United States
116	The University of Vermont Medical Center Inc	Burlington	Vermont	United States
117	Virginia Commonwealth University Health System	Richmond	Virginia	United States
118	Saint Mary's Medical Center	Huntington	West Virginia	United States
119	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States
120	Bellin Memorial Hospital, Inc.	Green Bay	Wisconsin	United States
121	Universitätsklinikum Krems	Krems		Austria
122	Universitair Ziekenhuis Brussel	Brussel		Belgium
123	Ziekenhuis Oost Limburg - Campus St.-Jan	Genk		Belgium
124	Centre Hospitalier Regional de la Citadelle	Liège		Belgium
125	Saint Paul's Hospital (Vancouver BC)	Vancouver	British Columbia	Canada
126	Hamilton General Hospital / Hamilton Health Sciences	Hamilton	Ontario	Canada
127	University of Ottawa Heart Institute	Ottawa	Ontario	Canada
128	Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)	Quebec		Canada
129	Hospital San Juan de Dios	Santiago		Chile
130	Grantham Hospital	Hong Kong		China
131	Princess Margaret Hospital	Hong Kong		China
132	Rigshospitalet	København		Denmark
133	Helsinki University Hospital	Helsinki		Finland
134	Turun Yliopistollinen keskussairaala	Turku		Finland
135	Centre Hospitalier Régional Universitaire de Lille	Lille		France
136	Hôpital de la Timone - Centre Hospitalier Universitaire de Marseille	Marseille		France
137	Nouvelles Cliniques Nantaises	Nantes		France
138	CHU Hôpiteaux de Rouen - Hôpital Charles Nicolle	Rouen Cedex 1		France
139	Centre Hospitalier Universitaire Saint Étienne - Hôpital Nord	Saint Priest en Jarez		France
140	Universitäts-Herz-Zentrum Freiburg - Bad Krozingen	Bad Krozingen		Germany
141	Universitätsmedizin Rostock	Rostock		Germany
142	University General Hospital of Heraklion	Heraklion		Greece
143	University Hospital of Ioannina	Ioannina		Greece
144	Onassis Cardiac Surgery Center	Kallithea		Greece
145	Rabin Medical Center - Beilinson Hospital	Petah Tikva		Israel
146	Chaim Sheba Medical Center	Ramat Gan		Israel
147	Policlinico Sant' Orsola - Malpighi	Bologna		Italy
148	Azienda Ospedaliera Spedali Civili di Brescia	Brescia		Italy
149	Presidio Ospedaliero Sant'Anna	Como		Italy
150	Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello	Pisa		Italy
151	Hospital Sultanah Bahiyah	Alor Setar	Kedah	Malaysia
152	Institut Jantung Negara - National Heart Institute	Kuala Lumpur		Malaysia
153	Universiti Malaya Medical Centre	Kuala Lumpur		Malaysia
154	Catharina Ziekenhuis	Eindhoven		Netherlands
155	St. Antonius Ziekenhuis	Nieuwegein		Netherlands
156	Helse Bergen HF - Haukeland Universitetssjukehus	Bergen		Norway
157	Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie	Lublin		Poland
158	Szpital Kliniczny Przemienienia Panskiego	Poznań		Poland
159	Hospital de Santa Maria-Centro Hospitalar Lisboa Norte, EPE	Lisboa		Portugal
160	Centro Hospitalar do Porto	Porto		Portugal
161	King Faisal Specialist Hospital & Research Center	Riyadh		Saudi Arabia
162	Changi General Hospital	Singapore		Singapore
163	National Heart Centre Singapore	Singapore		Singapore
164	Stredoslovensky ustav srdcovych a cievnych chorob a.s	Banska Bystrica		Slovakia
165	Narodny ustav srdcovych a cievnych chorob, a.s. (NUSCH)	Bratislava 37		Slovakia
166	Vychodoslovensky ustav srdcovych a cievnych chorob, a.s.	Kosice		Slovakia
167	Hospital Marqués de Valdecilla	Santander	Cantabria	Spain
168	Hospital Universitari Bellvitge	Barcelona		Spain
169	Hospital Universitario La Paz	Madrid		Spain
170	Hospital Universitario Ramón y Cajal	Madrid		Spain
171	Alingsås Lasarett	Goteborg		Sweden
172	Sahlgrenska Universitetssjukhuset	Goteborg		Sweden
173	Karolinska Universitetssjukhuset	Stockholm		Sweden
174	Sjukhuset i Varberg	Varberg		Sweden
175	Centre Hospitalier Universitaire Vaudois	Lausanne		Switzerland
176	Cardiocentro Ticino	Lugano		Switzerland
177	Kantonsspital St.Gallen	St. Gallen		Switzerland
178	Liverpool Heart and Chest Hospital NHS Foundation Trust	Liverpool		United Kingdom
179	Royal Brompton & Harefield NHS Foundation Trust - Harefield Hospital	London		United Kingdom
180	Central Manchester University Hospitals NHS - Manchester Royal Infirmary	Manchester		United Kingdom
181	The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital	Newcastle Upon Tyne		United Kingdom

Sponsors and Collaborators

Medtronic Cardiac Rhythm and Heart Failure
The Cleveland Clinic

Investigators

Study Chair: Bruce Wilkoff, MD, The Cleveland Clinic
Principal Investigator: Khaldoun Tarakji, MD, The Cleveland Clinic

Study Documents (Full-Text)

Study Protocol and Statistical Analysis Plan - Jul 31, 2018

More Information

Publications

None provided.

Responsible Party:

Medtronic Cardiac Rhythm and Heart Failure

ClinicalTrials.gov Identifier:

NCT02277990

Other Study ID Numbers:

WRAP-IT

First Posted:

Oct 29, 2014

Last Update Posted:

Nov 5, 2019

Last Verified:

Oct 1, 2019

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Infections

Communicable Diseases

Anti-Bacterial Agents

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	There were 92 total patients that were enrolled into the study, but not randomized. After enrollment, but prior to randomization, 2 patients died, 31 patients were found to not meet eligibility criteria, 50 patients withdrew, 1 investigator withdrew the patient and 8 patients had an other or unknown reason for not being randomized.

Arm/Group Title	TYRX Envelope	Control
Arm/Group Description	The Medtronic TYRX Absorbable Antibacterial Envelope is an absorbable sterile prosthesis designed to hold a pacemaker pulse generator or defibrillator to create a stable environment when implanted in the body. The purpose of the absorbable coating is to act as a carrier for the antimicrobial agents. TYRX Absorbable Antibacterial Envelope	No TYRX envelope, bare CIED
Period Title: Overall Study
STARTED	3495	3488
COMPLETED	3129	3112
NOT COMPLETED	366	376

Baseline Characteristics

Arm/Group Title	TYRX Envelope	Control	Total
Arm/Group Description	The Medtronic TYRX Absorbable Antibacterial Envelope is an absorbable sterile prosthesis designed to hold a pacemaker pulse generator or defibrillator to create a stable environment when implanted in the body. The purpose of the absorbable coating is to act as a carrier for the antimicrobial agents. TYRX Absorbable Antibacterial Envelope	No TYRX envelope, bare CIED	Total of all reporting groups
Overall Participants	3495	3488	6983
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.0 (12.6)	70.1 (12.4)	70.1 (12.5)
Sex: Female, Male (Count of Participants)
Female	997 28.5%	976 28%	1973 28.3%
Male	2498 71.5%	2512 72%	5010 71.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	8 0.2%	4 0.1%	12 0.2%
Asian	97 2.8%	91 2.6%	188 2.7%
Native Hawaiian or Other Pacific Islander	9 0.3%	7 0.2%	16 0.2%
Black or African American	202 5.8%	207 5.9%	409 5.9%
White	2698 77.2%	2691 77.2%	5389 77.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	476 13.6%	485 13.9%	961 13.8%
Region of Enrollment (participants) [Number]
Singapore	11 0.3%	8 0.2%	19 0.3%
United States	2440 69.8%	2441 70%	4881 69.9%
Malaysia	42 1.2%	41 1.2%	83 1.2%
Portugal	20 0.6%	17 0.5%	37 0.5%
Greece	45 1.3%	43 1.2%	88 1.3%
Saudi Arabia	11 0.3%	10 0.3%	21 0.3%
Austria	29 0.8%	29 0.8%	58 0.8%
Netherlands	70 2%	69 2%	139 2%
Sweden	45 1.3%	47 1.3%	92 1.3%
China	18 0.5%	19 0.5%	37 0.5%
Poland	18 0.5%	16 0.5%	34 0.5%
Slovakia	29 0.8%	31 0.9%	60 0.9%
Chile	2 0.1%	3 0.1%	5 0.1%
France	94 2.7%	94 2.7%	188 2.7%
United Kingdom	135 3.9%	141 4%	276 4%
Switzerland	30 0.9%	33 0.9%	63 0.9%
Spain	52 1.5%	48 1.4%	100 1.4%
Canada	131 3.7%	131 3.8%	262 3.8%
Belgium	36 1%	35 1%	71 1%
Norway	32 0.9%	32 0.9%	64 0.9%
Finland	24 0.7%	23 0.7%	47 0.7%
Denmark	34 1%	36 1%	70 1%
Italy	88 2.5%	86 2.5%	174 2.5%
Israel	47 1.3%	44 1.3%	91 1.3%
Germany	12 0.3%	11 0.3%	23 0.3%

Outcome Measures

1. Primary Outcome

Title	12 Month Kaplan-Meier Estimate of Major CIED Infection Rate
Description	CIED infections are defined as (1) superficial cellulitis in the region of the CIED pocket with wound dehiscence, erosion, or purulent drainage, (2) deep incisional or organ/space (generator pocket) surgical site infection that meets the Centers for Disease Control and Prevention criteria, independent from time of surgery, (3) persistent bacteremia, or (4) endocarditis. Major CIED infections are defined as a CIED infection resulting in one or more of the following: CIED system removal Any invasive procedure (e.g. pocket opened) without system removal Treatment with antibiotic therapy if the subject is not a candidate for system removal and infection recurrence after completion of antibiotic therapy or evidence of deep infection with wound dehiscence, erosion, or purulent drainage Death
Time Frame	Implant to 12 months

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	TYRX Envelope	Control
Arm/Group Description	The Medtronic TYRX Absorbable Antibacterial Envelope is an absorbable sterile prosthesis designed to hold a pacemaker pulse generator or defibrillator to create a stable environment when implanted in the body. The purpose of the absorbable coating is to act as a carrier for the antimicrobial agents. TYRX Absorbable Antibacterial Envelope	No TYRX envelope, bare CIED
Measure Participants	3495	3488
Number (95% Confidence Interval) [Percentage of subjects]	0.7	1.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TYRX Envelope, Control
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0406
	Comments	The 0.05 critical value for assessing the primary endpoint was adjusted to 0.0488, to account for a planned interim analysis.
	Method	Regression, Cox
	Comments	The Cox regression was stratified according to device type (pacemaker or CRT-P vs. ICD or CRT-D).

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95.12% 0.36 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	12 Month Kaplan-Meier Estimate of Major or Minor CIED Infection
Description	Major CIED infections are defined above. Minor CIED infections are defined as CIED infections that do not meet the definition of a major CIED infection
Time Frame	Implant to 12 months

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	TYRX Envelope	Control
Arm/Group Description	The Medtronic TYRX Absorbable Antibacterial Envelope is an absorbable sterile prosthesis designed to hold a pacemaker pulse generator or defibrillator to create a stable environment when implanted in the body. The purpose of the absorbable coating is to act as a carrier for the antimicrobial agents. TYRX Absorbable Antibacterial Envelope	No TYRX envelope, bare CIED
Measure Participants	3495	3488
Number (95% Confidence Interval) [Percentage of subjects]	1.4	2.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TYRX Envelope, Control
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0248
	Comments
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95.12% 0.47 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	12 Month Kaplan-Meier Estimate of a CIED Procedure Related or System Related Complication
Description	A CIED system related event is defined as an adverse event related to the CIED system which includes the device, leads, implant tool(s), programmer, or TYRX envelope (if applicable) A CIED procedure related event is defined as an adverse event that occurs due to any procedure related to the implantation or surgical modification of the system including the TYRX envelope (if applicable) A procedure or system related complication is defined as an adverse event related to a CIED procedure or the CIED system that results in at least one of the following: Death,Termination of significant device function, Invasive intervention
Time Frame	Implant to 12 months

Outcome Measure Data

Analysis Population Description
Per the Statistical Analysis Plan, the statistical inference for this objective was based on the As-Treated cohort instead of the Intention-to-Treat cohort. Per the cohort definition, subjects are analyzed based on the treatment (envelope or no envelope) and the device class (low or high power) that was actually received.

Arm/Group Title	TYRX Envelope	Control
Arm/Group Description	The Medtronic TYRX Absorbable Antibacterial Envelope is an absorbable sterile prosthesis designed to hold a pacemaker pulse generator or defibrillator to create a stable environment when implanted in the body. The purpose of the absorbable coating is to act as a carrier for the antimicrobial agents. TYRX Absorbable Antibacterial Envelope	No TYRX envelope, bare CIED
Measure Participants	3396	3507
Number [Percentage of subjects]	6.0	6.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TYRX Envelope, Control
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority test was performed on the as-treated cohort, per the statistical analysis plan. The non-inferiority margin for the hazard ratio was 1.33 (i.e., the hazard ratio for complications in the envelope group vs. the control group must be significantly lower than 1.33).

Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95.12% 0.77 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Kaplan-Meier Estimate of a Major Infection Throughout Follow-up
Description	CIED infections are defined as (1) superficial cellulitis in the region of the CIED pocket with wound dehiscence, erosion, or purulent drainage, (2) deep incisional or organ/space (generator pocket) surgical site infection that meets the Centers for Disease Control and Prevention criteria, independent from time of surgery, (3) persistent bacteremia, or (4) endocarditis. Major CIED infections are defined as a CIED infection resulting in one or more of the following: CIED system removal Any invasive procedure (e.g. pocket opened) without system removal Treatment with antibiotic therapy if the subject is not a candidate for system removal and infection recurrence after completion of antibiotic therapy or evidence of deep infection with wound dehiscence, erosion, or purulent drainage Death
Time Frame	Throughout study follow-up Kaplan-Meier Estimate is at 36 Months

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	TYRX Envelope	Control
Arm/Group Description	The Medtronic TYRX Absorbable Antibacterial Envelope is an absorbable sterile prosthesis designed to hold a pacemaker pulse generator or defibrillator to create a stable environment when implanted in the body. The purpose of the absorbable coating is to act as a carrier for the antimicrobial agents. TYRX Absorbable Antibacterial Envelope	No TYRX envelope, bare CIED
Measure Participants	3495	3488
Number (95% Confidence Interval) [Percentage of subjects]	1.3	1.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TYRX Envelope, Control
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0402
	Comments
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95.12% 0.40 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

	TYRX Envelope		Control
Time Frame	Assessed from baseline visit to 36-month follow-up visit
Adverse Event Reporting Description

Arm/Group Title	TYRX Envelope		Control
Arm/Group Description	The Medtronic TYRX Absorbable Antibacterial Envelope is an absorbable sterile prosthesis designed to hold a pacemaker pulse generator or defibrillator to create a stable environment when implanted in the body. The purpose of the absorbable coating is to act as a carrier for the antimicrobial agents. TYRX Absorbable Antibacterial Envelope		No TYRX envelope, bare CIED
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	349/3495 (10%)		365/3488 (10.5%)
Serious Adverse Events
	TYRX Envelope		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1553/3495 (44.4%)		1548/3488 (44.4%)
Blood and lymphatic system disorders
Anaemia	28/3495 (0.8%)		26/3488 (0.7%)
Anaemia folate deficiency	1/3495 (0%)		0/3488 (0%)
Autoimmune haemolytic anaemia	1/3495 (0%)		0/3488 (0%)
Coagulopathy	2/3495 (0.1%)		1/3488 (0%)
Disseminated intravascular coagulation	0/3495 (0%)		1/3488 (0%)
Haemolytic anaemia	0/3495 (0%)		1/3488 (0%)
Haemorrhagic anaemia	9/3495 (0.3%)		3/3488 (0.1%)
Immune thrombocytopenic purpura	1/3495 (0%)		1/3488 (0%)
Iron deficiency anaemia	4/3495 (0.1%)		10/3488 (0.3%)
Microcytic anaemia	2/3495 (0.1%)		0/3488 (0%)
Neutropenia	0/3495 (0%)		1/3488 (0%)
Normocytic anaemia	1/3495 (0%)		0/3488 (0%)
Pancytopenia	4/3495 (0.1%)		0/3488 (0%)
Thrombocytopenia	2/3495 (0.1%)		1/3488 (0%)
Cardiac disorders
Acute coronary syndrome	2/3495 (0.1%)		4/3488 (0.1%)
Acute left ventricular failure	1/3495 (0%)		1/3488 (0%)
Acute myocardial infarction	32/3495 (0.9%)		35/3488 (1%)
Angina pectoris	20/3495 (0.6%)		29/3488 (0.8%)
Angina unstable	15/3495 (0.4%)		10/3488 (0.3%)
Aortic valve disease	1/3495 (0%)		2/3488 (0.1%)
Aortic valve incompetence	4/3495 (0.1%)		0/3488 (0%)
Aortic valve stenosis	3/3495 (0.1%)		3/3488 (0.1%)
Arrhythmia	5/3495 (0.1%)		8/3488 (0.2%)
Arrhythmia supraventricular	2/3495 (0.1%)		4/3488 (0.1%)
Arteriosclerosis coronary artery	0/3495 (0%)		1/3488 (0%)
Atrial fibrillation	127/3495 (3.6%)		136/3488 (3.9%)
Atrial flutter	21/3495 (0.6%)		18/3488 (0.5%)
Atrial tachycardia	6/3495 (0.2%)		6/3488 (0.2%)
Atrial thrombosis	2/3495 (0.1%)		0/3488 (0%)
Atrioventricular block second degree	1/3495 (0%)		0/3488 (0%)
Bundle branch block left	0/3495 (0%)		1/3488 (0%)
Cardiac arrest	36/3495 (1%)		23/3488 (0.7%)
Cardiac asthma	1/3495 (0%)		0/3488 (0%)
Cardiac disorder	1/3495 (0%)		2/3488 (0.1%)
Cardiac failure	131/3495 (3.7%)		131/3488 (3.8%)
Cardiac failure acute	35/3495 (1%)		48/3488 (1.4%)
Cardiac failure chronic	14/3495 (0.4%)		26/3488 (0.7%)
Cardiac failure congestive	186/3495 (5.3%)		200/3488 (5.7%)
Cardiac perforation	1/3495 (0%)		1/3488 (0%)
Cardiac tamponade	3/3495 (0.1%)		5/3488 (0.1%)
Cardiac valve disease	2/3495 (0.1%)		0/3488 (0%)
Cardio-respiratory arrest	13/3495 (0.4%)		10/3488 (0.3%)
Cardiogenic shock	18/3495 (0.5%)		15/3488 (0.4%)
Cardiomyopathy	19/3495 (0.5%)		15/3488 (0.4%)
Cardiomyopathy alcoholic	1/3495 (0%)		0/3488 (0%)
Cardiopulmonary failure	1/3495 (0%)		0/3488 (0%)
Cardiorenal syndrome	2/3495 (0.1%)		6/3488 (0.2%)
Cardiovascular disorder	0/3495 (0%)		1/3488 (0%)
Chronic left ventricular failure	5/3495 (0.1%)		4/3488 (0.1%)
Congestive cardiomyopathy	0/3495 (0%)		6/3488 (0.2%)
Coronary artery disease	32/3495 (0.9%)		32/3488 (0.9%)
Coronary artery insufficiency	0/3495 (0%)		1/3488 (0%)
Coronary artery occlusion	0/3495 (0%)		3/3488 (0.1%)
Coronary artery stenosis	1/3495 (0%)		3/3488 (0.1%)
Hypertensive heart disease	0/3495 (0%)		2/3488 (0.1%)
Intracardiac thrombus	0/3495 (0%)		6/3488 (0.2%)
Ischaemic cardiomyopathy	9/3495 (0.3%)		18/3488 (0.5%)
Left ventricular dysfunction	4/3495 (0.1%)		3/3488 (0.1%)
Left ventricular failure	3/3495 (0.1%)		4/3488 (0.1%)
Mitral valve disease	3/3495 (0.1%)		1/3488 (0%)
Mitral valve incompetence	8/3495 (0.2%)		11/3488 (0.3%)
Mitral valve stenosis	1/3495 (0%)		0/3488 (0%)
Myocardial infarction	11/3495 (0.3%)		10/3488 (0.3%)
Myocardial ischaemia	3/3495 (0.1%)		3/3488 (0.1%)
Palpitations	4/3495 (0.1%)		3/3488 (0.1%)
Pericardial effusion	11/3495 (0.3%)		7/3488 (0.2%)
Pulseless electrical activity	4/3495 (0.1%)		1/3488 (0%)
Rheumatic heart disease	0/3495 (0%)		1/3488 (0%)
Right atrial dilatation	0/3495 (0%)		1/3488 (0%)
Right ventricular failure	2/3495 (0.1%)		2/3488 (0.1%)
Sinus node dysfunction	1/3495 (0%)		1/3488 (0%)
Supraventricular tachycardia	5/3495 (0.1%)		8/3488 (0.2%)
Tachyarrhythmia	1/3495 (0%)		0/3488 (0%)
Tachycardia	9/3495 (0.3%)		6/3488 (0.2%)
Torsade de pointes	0/3495 (0%)		1/3488 (0%)
Tricuspid valve incompetence	4/3495 (0.1%)		1/3488 (0%)
Ventricular arrhythmia	19/3495 (0.5%)		10/3488 (0.3%)
Ventricular extrasystoles	2/3495 (0.1%)		7/3488 (0.2%)
Ventricular fibrillation	22/3495 (0.6%)		26/3488 (0.7%)
Ventricular tachyarrhythmia	1/3495 (0%)		0/3488 (0%)
Ventricular tachycardia	92/3495 (2.6%)		92/3488 (2.6%)
Congenital, familial and genetic disorders
Adenomatous polyposis coli	1/3495 (0%)		0/3488 (0%)
Atrial septal defect	0/3495 (0%)		1/3488 (0%)
Congenital aortic valve stenosis	0/3495 (0%)		1/3488 (0%)
Hypertrophic cardiomyopathy	0/3495 (0%)		1/3488 (0%)
Myotonic dystrophy	0/3495 (0%)		1/3488 (0%)
Phimosis	1/3495 (0%)		0/3488 (0%)
Pyloric stenosis	0/3495 (0%)		1/3488 (0%)
Ear and labyrinth disorders
Deafness neurosensory	1/3495 (0%)		0/3488 (0%)
Meniere's disease	0/3495 (0%)		1/3488 (0%)
Otosclerosis	1/3495 (0%)		0/3488 (0%)
Vertigo	1/3495 (0%)		4/3488 (0.1%)
Vertigo labyrinthine	0/3495 (0%)		1/3488 (0%)
Endocrine disorders
Adrenal insufficiency	0/3495 (0%)		1/3488 (0%)
Goitre	0/3495 (0%)		1/3488 (0%)
Hyperparathyroidism	1/3495 (0%)		0/3488 (0%)
Hyperthyroidism	0/3495 (0%)		1/3488 (0%)
Hypothyroidism	3/3495 (0.1%)		0/3488 (0%)
Thyroid mass	1/3495 (0%)		0/3488 (0%)
Toxic nodular goitre	1/3495 (0%)		0/3488 (0%)
Eye disorders
Cataract	21/3495 (0.6%)		15/3488 (0.4%)
Cataract nuclear	1/3495 (0%)		1/3488 (0%)
Conjunctival haemorrhage	0/3495 (0%)		1/3488 (0%)
Diplopia	0/3495 (0%)		1/3488 (0%)
Ectropion	0/3495 (0%)		1/3488 (0%)
Entropion	1/3495 (0%)		0/3488 (0%)
Exfoliation syndrome	1/3495 (0%)		1/3488 (0%)
Eye haemorrhage	1/3495 (0%)		0/3488 (0%)
Glaucoma	0/3495 (0%)		1/3488 (0%)
Lens dislocation	1/3495 (0%)		0/3488 (0%)
Retinal artery occlusion	0/3495 (0%)		1/3488 (0%)
Retinal oedema	1/3495 (0%)		0/3488 (0%)
Strabismus	1/3495 (0%)		1/3488 (0%)
Visual impairment	1/3495 (0%)		1/3488 (0%)
Gastrointestinal disorders
Abdominal compartment syndrome	1/3495 (0%)		0/3488 (0%)
Abdominal discomfort	2/3495 (0.1%)		0/3488 (0%)
Abdominal hernia	3/3495 (0.1%)		2/3488 (0.1%)
Abdominal incarcerated hernia	1/3495 (0%)		1/3488 (0%)
Abdominal pain	5/3495 (0.1%)		9/3488 (0.3%)
Abdominal pain lower	1/3495 (0%)		1/3488 (0%)
Abdominal pain upper	1/3495 (0%)		2/3488 (0.1%)
Abdominal wall haematoma	2/3495 (0.1%)		1/3488 (0%)
Acute abdomen	1/3495 (0%)		0/3488 (0%)
Alcoholic pancreatitis	0/3495 (0%)		2/3488 (0.1%)
Anal fistula	1/3495 (0%)		0/3488 (0%)
Ascites	2/3495 (0.1%)		3/3488 (0.1%)
Barrett's oesophagus	1/3495 (0%)		0/3488 (0%)
Colitis	4/3495 (0.1%)		6/3488 (0.2%)
Colitis ischaemic	4/3495 (0.1%)		2/3488 (0.1%)
Colitis ulcerative	1/3495 (0%)		0/3488 (0%)
Diarrhoea	0/3495 (0%)		2/3488 (0.1%)
Dieulafoy's vascular malformation	0/3495 (0%)		1/3488 (0%)
Diverticular perforation	0/3495 (0%)		1/3488 (0%)
Diverticulum	2/3495 (0.1%)		2/3488 (0.1%)
Diverticulum intestinal	0/3495 (0%)		2/3488 (0.1%)
Diverticulum intestinal haemorrhagic	2/3495 (0.1%)		0/3488 (0%)
Diverticulum oesophageal	1/3495 (0%)		0/3488 (0%)
Duodenal ulcer	2/3495 (0.1%)		0/3488 (0%)
Duodenal ulcer haemorrhage	0/3495 (0%)		1/3488 (0%)
Dyspepsia	0/3495 (0%)		1/3488 (0%)
Dysphagia	1/3495 (0%)		8/3488 (0.2%)
Enteritis	1/3495 (0%)		0/3488 (0%)
Enterocele	0/3495 (0%)		1/3488 (0%)
Enterocolitis	1/3495 (0%)		0/3488 (0%)
Faecaloma	1/3495 (0%)		0/3488 (0%)
Gallstone ileus	0/3495 (0%)		1/3488 (0%)
Gastric haemorrhage	1/3495 (0%)		0/3488 (0%)
Gastric hypomotility	1/3495 (0%)		0/3488 (0%)
Gastric perforation	0/3495 (0%)		1/3488 (0%)
Gastritis	1/3495 (0%)		0/3488 (0%)
Gastritis erosive	0/3495 (0%)		1/3488 (0%)
Gastroduodenitis	1/3495 (0%)		0/3488 (0%)
Gastrointestinal haemorrhage	20/3495 (0.6%)		33/3488 (0.9%)
Gastrointestinal vascular malformation haemorrhagic	0/3495 (0%)		1/3488 (0%)
Gastrooesophageal reflux disease	4/3495 (0.1%)		1/3488 (0%)
Gingival bleeding	1/3495 (0%)		0/3488 (0%)
Haematochezia	2/3495 (0.1%)		2/3488 (0.1%)
Haemorrhoidal haemorrhage	1/3495 (0%)		2/3488 (0.1%)
Haemorrhoids	1/3495 (0%)		0/3488 (0%)
Hiatus hernia	1/3495 (0%)		0/3488 (0%)
Ileal perforation	1/3495 (0%)		0/3488 (0%)
Ileus	3/3495 (0.1%)		0/3488 (0%)
Incarcerated umbilical hernia	1/3495 (0%)		0/3488 (0%)
Inguinal hernia	7/3495 (0.2%)		19/3488 (0.5%)
Inguinal hernia strangulated	1/3495 (0%)		0/3488 (0%)
Inguinal hernia, obstructive	1/3495 (0%)		0/3488 (0%)
Intestinal obstruction	0/3495 (0%)		3/3488 (0.1%)
Intestinal perforation	0/3495 (0%)		2/3488 (0.1%)
Intestinal polyp	0/3495 (0%)		1/3488 (0%)
Intra-abdominal haemorrhage	1/3495 (0%)		0/3488 (0%)
Irritable bowel syndrome	1/3495 (0%)		0/3488 (0%)
Large intestinal obstruction	1/3495 (0%)		0/3488 (0%)
Large intestine polyp	3/3495 (0.1%)		5/3488 (0.1%)
Lower gastrointestinal haemorrhage	5/3495 (0.1%)		3/3488 (0.1%)
Melaena	3/3495 (0.1%)		2/3488 (0.1%)
Mouth haemorrhage	1/3495 (0%)		0/3488 (0%)
Nausea	0/3495 (0%)		1/3488 (0%)
Obstructive pancreatitis	1/3495 (0%)		4/3488 (0.1%)
Oesophageal food impaction	0/3495 (0%)		1/3488 (0%)
Oesophageal motility disorder	0/3495 (0%)		1/3488 (0%)
Oesophageal obstruction	0/3495 (0%)		2/3488 (0.1%)
Oesophageal stenosis	0/3495 (0%)		1/3488 (0%)
Oesophageal ulcer haemorrhage	0/3495 (0%)		1/3488 (0%)
Pancreatic pseudocyst	0/3495 (0%)		1/3488 (0%)
Pancreatitis	3/3495 (0.1%)		3/3488 (0.1%)
Pancreatitis acute	4/3495 (0.1%)		3/3488 (0.1%)
Pancreatitis relapsing	1/3495 (0%)		0/3488 (0%)
Peptic ulcer	1/3495 (0%)		0/3488 (0%)
Peptic ulcer haemorrhage	0/3495 (0%)		1/3488 (0%)
Peritoneal haemorrhage	1/3495 (0%)		0/3488 (0%)
Proctalgia	1/3495 (0%)		0/3488 (0%)
Rectal discharge	1/3495 (0%)		0/3488 (0%)
Rectal haemorrhage	5/3495 (0.1%)		2/3488 (0.1%)
Retroperitoneal haematoma	1/3495 (0%)		0/3488 (0%)
Retroperitoneal haemorrhage	0/3495 (0%)		1/3488 (0%)
Small intestinal obstruction	12/3495 (0.3%)		7/3488 (0.2%)
Spigelian hernia	1/3495 (0%)		0/3488 (0%)
Umbilical hernia	2/3495 (0.1%)		3/3488 (0.1%)
Upper gastrointestinal haemorrhage	7/3495 (0.2%)		8/3488 (0.2%)
Vomiting	3/3495 (0.1%)		0/3488 (0%)
General disorders
Accidental death	2/3495 (0.1%)		0/3488 (0%)
Adverse drug reaction	0/3495 (0%)		1/3488 (0%)
Asthenia	8/3495 (0.2%)		5/3488 (0.1%)
Cardiac death	2/3495 (0.1%)		1/3488 (0%)
Catheter site haematoma	0/3495 (0%)		1/3488 (0%)
Chest discomfort	2/3495 (0.1%)		1/3488 (0%)
Chest pain	23/3495 (0.7%)		34/3488 (1%)
Complication associated with device	0/3495 (0%)		1/3488 (0%)
Complication of device insertion	1/3495 (0%)		0/3488 (0%)
Death	37/3495 (1.1%)		32/3488 (0.9%)
Device embolisation	0/3495 (0%)		1/3488 (0%)
Fatigue	0/3495 (0%)		2/3488 (0.1%)
Gait disturbance	0/3495 (0%)		1/3488 (0%)
General physical health deterioration	2/3495 (0.1%)		1/3488 (0%)
Generalised oedema	0/3495 (0%)		4/3488 (0.1%)
Hernia	1/3495 (0%)		2/3488 (0.1%)
Impaired healing	1/3495 (0%)		0/3488 (0%)
Implant site bruising	1/3495 (0%)		0/3488 (0%)
Implant site dehiscence	4/3495 (0.1%)		1/3488 (0%)
Implant site dermatitis	0/3495 (0%)		1/3488 (0%)
Implant site discharge	1/3495 (0%)		0/3488 (0%)
Implant site erosion	1/3495 (0%)		0/3488 (0%)
Implant site erythema	2/3495 (0.1%)		1/3488 (0%)
Implant site haematoma	29/3495 (0.8%)		25/3488 (0.7%)
Implant site haemorrhage	0/3495 (0%)		3/3488 (0.1%)
Implant site irritation	1/3495 (0%)		0/3488 (0%)
Implant site pain	10/3495 (0.3%)		17/3488 (0.5%)
Implant site swelling	1/3495 (0%)		0/3488 (0%)
Incarcerated hernia	1/3495 (0%)		0/3488 (0%)
Inflammation	0/3495 (0%)		1/3488 (0%)
Malaise	2/3495 (0.1%)		1/3488 (0%)
Mass	0/3495 (0%)		1/3488 (0%)
Medical device discomfort	0/3495 (0%)		1/3488 (0%)
Medical device site joint pain	1/3495 (0%)		0/3488 (0%)
Mucosal inflammation	0/3495 (0%)		1/3488 (0%)
Multiple organ dysfunction syndrome	4/3495 (0.1%)		5/3488 (0.1%)
Non-cardiac chest pain	13/3495 (0.4%)		14/3488 (0.4%)
Oedema	0/3495 (0%)		1/3488 (0%)
Oedema peripheral	3/3495 (0.1%)		0/3488 (0%)
Pacemaker syndrome	1/3495 (0%)		0/3488 (0%)
Peripheral swelling	1/3495 (0%)		1/3488 (0%)
Phantom shocks	2/3495 (0.1%)		4/3488 (0.1%)
Polyp	0/3495 (0%)		1/3488 (0%)
Pyrexia	5/3495 (0.1%)		5/3488 (0.1%)
Sudden cardiac death	1/3495 (0%)		0/3488 (0%)
Sudden death	1/3495 (0%)		2/3488 (0.1%)
Terminal state	1/3495 (0%)		1/3488 (0%)
Ulcer	0/3495 (0%)		1/3488 (0%)
Vascular stent stenosis	0/3495 (0%)		3/3488 (0.1%)
Vascular stent thrombosis	0/3495 (0%)		2/3488 (0.1%)
Hepatobiliary disorders
Autoimmune hepatitis	1/3495 (0%)		0/3488 (0%)
Bile duct stenosis	2/3495 (0.1%)		0/3488 (0%)
Bile duct stone	1/3495 (0%)		1/3488 (0%)
Biliary colic	2/3495 (0.1%)		1/3488 (0%)
Biliary dyskinesia	1/3495 (0%)		0/3488 (0%)
Cholangitis	0/3495 (0%)		1/3488 (0%)
Cholecystitis	8/3495 (0.2%)		0/3488 (0%)
Cholecystitis acute	3/3495 (0.1%)		5/3488 (0.1%)
Cholecystitis chronic	0/3495 (0%)		2/3488 (0.1%)
Cholelithiasis	9/3495 (0.3%)		7/3488 (0.2%)
Hepatic cirrhosis	1/3495 (0%)		3/3488 (0.1%)
Hepatic congestion	1/3495 (0%)		0/3488 (0%)
Hepatic cyst	0/3495 (0%)		1/3488 (0%)
Hepatic lesion	0/3495 (0%)		1/3488 (0%)
Hepatic mass	2/3495 (0.1%)		1/3488 (0%)
Hepatitis	1/3495 (0%)		1/3488 (0%)
Hepatitis acute	0/3495 (0%)		1/3488 (0%)
Hepatitis alcoholic	1/3495 (0%)		0/3488 (0%)
Hepatorenal syndrome	1/3495 (0%)		0/3488 (0%)
Hyperbilirubinaemia	0/3495 (0%)		1/3488 (0%)
Jaundice cholestatic	2/3495 (0.1%)		1/3488 (0%)
Liver injury	1/3495 (0%)		0/3488 (0%)
Non-alcoholic steatohepatitis	1/3495 (0%)		0/3488 (0%)
Immune system disorders
Anaphylactic reaction	2/3495 (0.1%)		0/3488 (0%)
Anaphylactic shock	2/3495 (0.1%)		0/3488 (0%)
Drug hypersensitivity	1/3495 (0%)		2/3488 (0.1%)
Hypersensitivity	1/3495 (0%)		2/3488 (0.1%)
Sarcoidosis	0/3495 (0%)		1/3488 (0%)
Infections and infestations
Abdominal abscess	0/3495 (0%)		2/3488 (0.1%)
Abdominal infection	0/3495 (0%)		1/3488 (0%)
Abdominal sepsis	1/3495 (0%)		1/3488 (0%)
Abscess	1/3495 (0%)		0/3488 (0%)
Abscess limb	1/3495 (0%)		0/3488 (0%)
Abscess neck	1/3495 (0%)		1/3488 (0%)
Acute sinusitis	0/3495 (0%)		1/3488 (0%)
Appendicitis	4/3495 (0.1%)		2/3488 (0.1%)
Arteriovenous graft site infection	0/3495 (0%)		1/3488 (0%)
Arthritis bacterial	2/3495 (0.1%)		1/3488 (0%)
Bacteraemia	7/3495 (0.2%)		2/3488 (0.1%)
Biliary sepsis	1/3495 (0%)		0/3488 (0%)
Breast cellulitis	0/3495 (0%)		1/3488 (0%)
Bronchitis	11/3495 (0.3%)		15/3488 (0.4%)
Bronchitis bacterial	1/3495 (0%)		0/3488 (0%)
Bronchitis viral	0/3495 (0%)		1/3488 (0%)
Cellulitis	31/3495 (0.9%)		41/3488 (1.2%)
Chronic sinusitis	1/3495 (0%)		1/3488 (0%)
Citrobacter sepsis	0/3495 (0%)		1/3488 (0%)
Clostridium difficile colitis	2/3495 (0.1%)		4/3488 (0.1%)
Clostridium difficile infection	3/3495 (0.1%)		4/3488 (0.1%)
Cryptosporidiosis infection	0/3495 (0%)		1/3488 (0%)
Cystitis	3/3495 (0.1%)		1/3488 (0%)
Dengue fever	0/3495 (0%)		1/3488 (0%)
Device related infection	6/3495 (0.2%)		12/3488 (0.3%)
Device related sepsis	1/3495 (0%)		0/3488 (0%)
Diabetic gangrene	0/3495 (0%)		2/3488 (0.1%)
Diarrhoea infectious	0/3495 (0%)		1/3488 (0%)
Diverticulitis	8/3495 (0.2%)		11/3488 (0.3%)
Emphysematous cholecystitis	0/3495 (0%)		1/3488 (0%)
Endocarditis	6/3495 (0.2%)		9/3488 (0.3%)
Endocarditis staphylococcal	0/3495 (0%)		1/3488 (0%)
Enterobacter sepsis	1/3495 (0%)		0/3488 (0%)
Enterococcal bacteraemia	1/3495 (0%)		1/3488 (0%)
Enterococcal infection	0/3495 (0%)		1/3488 (0%)
Enterococcal sepsis	0/3495 (0%)		1/3488 (0%)
Epididymitis	1/3495 (0%)		0/3488 (0%)
Erysipelas	0/3495 (0%)		1/3488 (0%)
Escherichia bacteraemia	2/3495 (0.1%)		0/3488 (0%)
Escherichia pyelonephritis	0/3495 (0%)		1/3488 (0%)
Escherichia urinary tract infection	3/3495 (0.1%)		1/3488 (0%)
Gangrene	5/3495 (0.1%)		2/3488 (0.1%)
Gastroenteritis	9/3495 (0.3%)		5/3488 (0.1%)
Gastroenteritis viral	4/3495 (0.1%)		3/3488 (0.1%)
Gastrointestinal infection	0/3495 (0%)		1/3488 (0%)
Graft infection	1/3495 (0%)		0/3488 (0%)
Groin abscess	1/3495 (0%)		0/3488 (0%)
Groin infection	1/3495 (0%)		1/3488 (0%)
Hepatitis C	0/3495 (0%)		1/3488 (0%)
Herpes sepsis	0/3495 (0%)		1/3488 (0%)
Herpes zoster	2/3495 (0.1%)		1/3488 (0%)
Implant site cellulitis	2/3495 (0.1%)		5/3488 (0.1%)
Implant site infection	24/3495 (0.7%)		44/3488 (1.3%)
Incision site cellulitis	0/3495 (0%)		1/3488 (0%)
Infected dermal cyst	1/3495 (0%)		1/3488 (0%)
Infected skin ulcer	2/3495 (0.1%)		1/3488 (0%)
Infection	0/3495 (0%)		3/3488 (0.1%)
Infectious colitis	0/3495 (0%)		1/3488 (0%)
Influenza	19/3495 (0.5%)		13/3488 (0.4%)
Infusion site infection	1/3495 (0%)		0/3488 (0%)
Intestinal sepsis	2/3495 (0.1%)		1/3488 (0%)
Kidney infection	0/3495 (0%)		1/3488 (0%)
Klebsiella bacteraemia	1/3495 (0%)		1/3488 (0%)
Labyrinthitis	1/3495 (0%)		0/3488 (0%)
Lemierre syndrome	0/3495 (0%)		1/3488 (0%)
Liver abscess	0/3495 (0%)		1/3488 (0%)
Localised infection	2/3495 (0.1%)		2/3488 (0.1%)
Lower respiratory tract infection	3/3495 (0.1%)		1/3488 (0%)
Lung infection	2/3495 (0.1%)		3/3488 (0.1%)
Mediastinitis	0/3495 (0%)		1/3488 (0%)
Meningitis viral	0/3495 (0%)		1/3488 (0%)
Metapneumovirus infection	1/3495 (0%)		0/3488 (0%)
Neutropenic sepsis	1/3495 (0%)		0/3488 (0%)
Oesophageal candidiasis	1/3495 (0%)		0/3488 (0%)
Orchitis	3/3495 (0.1%)		1/3488 (0%)
Osler's nodes	1/3495 (0%)		0/3488 (0%)
Osteomyelitis	6/3495 (0.2%)		4/3488 (0.1%)
Osteomyelitis chronic	1/3495 (0%)		1/3488 (0%)
Parotitis	0/3495 (0%)		1/3488 (0%)
Perirectal abscess	1/3495 (0%)		0/3488 (0%)
Peritonitis bacterial	0/3495 (0%)		1/3488 (0%)
Pharyngitis streptococcal	1/3495 (0%)		0/3488 (0%)
Pneumococcal bacteraemia	1/3495 (0%)		0/3488 (0%)
Pneumonia	118/3495 (3.4%)		112/3488 (3.2%)
Pneumonia bacterial	3/3495 (0.1%)		1/3488 (0%)
Pneumonia influenzal	0/3495 (0%)		1/3488 (0%)
Pneumonia klebsiella	1/3495 (0%)		0/3488 (0%)
Pneumonia legionella	0/3495 (0%)		2/3488 (0.1%)
Pneumonia pseudomonal	1/3495 (0%)		1/3488 (0%)
Pneumonia respiratory syncytial viral	0/3495 (0%)		1/3488 (0%)
Pneumonia staphylococcal	1/3495 (0%)		2/3488 (0.1%)
Pneumonia streptococcal	1/3495 (0%)		1/3488 (0%)
Pneumonia viral	1/3495 (0%)		0/3488 (0%)
Post procedural infection	2/3495 (0.1%)		0/3488 (0%)
Postoperative wound infection	1/3495 (0%)		0/3488 (0%)
Psoas abscess	0/3495 (0%)		1/3488 (0%)
Pulmonary sepsis	8/3495 (0.2%)		13/3488 (0.4%)
Pyelonephritis	3/3495 (0.1%)		2/3488 (0.1%)
Pyelonephritis acute	0/3495 (0%)		3/3488 (0.1%)
Pyuria	1/3495 (0%)		0/3488 (0%)
Respiratory syncytial virus infection	0/3495 (0%)		2/3488 (0.1%)
Respiratory tract infection	1/3495 (0%)		0/3488 (0%)
Retroperitoneal abscess	1/3495 (0%)		0/3488 (0%)
Rhinovirus infection	1/3495 (0%)		0/3488 (0%)
Sepsis	23/3495 (0.7%)		20/3488 (0.6%)
Septic shock	11/3495 (0.3%)		9/3488 (0.3%)
Staphylococcal bacteraemia	2/3495 (0.1%)		4/3488 (0.1%)
Staphylococcal infection	2/3495 (0.1%)		2/3488 (0.1%)
Staphylococcal sepsis	3/3495 (0.1%)		3/3488 (0.1%)
Stitch abscess	1/3495 (0%)		0/3488 (0%)
Stoma site cellulitis	1/3495 (0%)		0/3488 (0%)
Streptococcal bacteraemia	0/3495 (0%)		2/3488 (0.1%)
Streptococcal sepsis	0/3495 (0%)		1/3488 (0%)
Subcutaneous abscess	2/3495 (0.1%)		1/3488 (0%)
Syphilis	0/3495 (0%)		1/3488 (0%)
Tooth abscess	0/3495 (0%)		1/3488 (0%)
Tooth infection	2/3495 (0.1%)		0/3488 (0%)
Tracheostomy infection	0/3495 (0%)		1/3488 (0%)
Upper respiratory tract infection	4/3495 (0.1%)		3/3488 (0.1%)
Urinary tract infection	52/3495 (1.5%)		57/3488 (1.6%)
Urinary tract infection pseudomonal	1/3495 (0%)		1/3488 (0%)
Urosepsis	15/3495 (0.4%)		17/3488 (0.5%)
Varicella zoster virus infection	0/3495 (0%)		1/3488 (0%)
Viral infection	3/3495 (0.1%)		0/3488 (0%)
Vulvovaginal candidiasis	1/3495 (0%)		0/3488 (0%)
Wound infection	1/3495 (0%)		2/3488 (0.1%)
Wound infection bacterial	1/3495 (0%)		0/3488 (0%)
Wound infection pseudomonas	0/3495 (0%)		1/3488 (0%)
Wound infection staphylococcal	1/3495 (0%)		0/3488 (0%)
Injury, poisoning and procedural complications
Accidental overdose	1/3495 (0%)		0/3488 (0%)
Anaemia postoperative	1/3495 (0%)		1/3488 (0%)
Ankle fracture	4/3495 (0.1%)		7/3488 (0.2%)
Arteriovenous fistula maturation failure	1/3495 (0%)		0/3488 (0%)
Back injury	1/3495 (0%)		0/3488 (0%)
Bone contusion	1/3495 (0%)		0/3488 (0%)
Cardiac procedure complication	11/3495 (0.3%)		9/3488 (0.3%)
Cardiac vein dissection	3/3495 (0.1%)		1/3488 (0%)
Cardiac vein perforation	1/3495 (0%)		1/3488 (0%)
Cervical vertebral fracture	1/3495 (0%)		1/3488 (0%)
Clavicle fracture	1/3495 (0%)		0/3488 (0%)
Compression fracture	0/3495 (0%)		1/3488 (0%)
Concussion	1/3495 (0%)		0/3488 (0%)
Contusion	2/3495 (0.1%)		0/3488 (0%)
Coronary artery restenosis	1/3495 (0%)		0/3488 (0%)
Craniocerebral injury	3/3495 (0.1%)		3/3488 (0.1%)
Device deployment issue	2/3495 (0.1%)		2/3488 (0.1%)
Device difficult to use	1/3495 (0%)		1/3488 (0%)
Device use issue	2/3495 (0.1%)		1/3488 (0%)
Dislocation of sternum	0/3495 (0%)		1/3488 (0%)
Eye injury	1/3495 (0%)		0/3488 (0%)
Facial bones fracture	0/3495 (0%)		1/3488 (0%)
Fall	9/3495 (0.3%)		12/3488 (0.3%)
Femoral neck fracture	3/3495 (0.1%)		4/3488 (0.1%)
Femur fracture	9/3495 (0.3%)		7/3488 (0.2%)
Foot fracture	1/3495 (0%)		1/3488 (0%)
Fractured sacrum	0/3495 (0%)		1/3488 (0%)
Graft thrombosis	0/3495 (0%)		1/3488 (0%)
Gun shot wound	0/3495 (0%)		1/3488 (0%)
Hand fracture	0/3495 (0%)		1/3488 (0%)
Head injury	1/3495 (0%)		2/3488 (0.1%)
Heat exhaustion	1/3495 (0%)		0/3488 (0%)
Hip fracture	15/3495 (0.4%)		11/3488 (0.3%)
Humerus fracture	3/3495 (0.1%)		4/3488 (0.1%)
Incision site haematoma	1/3495 (0%)		0/3488 (0%)
Incision site haemorrhage	3/3495 (0.1%)		4/3488 (0.1%)
Incisional hernia	0/3495 (0%)		1/3488 (0%)
Injury	1/3495 (0%)		0/3488 (0%)
Intentional overdose	0/3495 (0%)		1/3488 (0%)
Jaw fracture	0/3495 (0%)		1/3488 (0%)
Joint dislocation	1/3495 (0%)		2/3488 (0.1%)
Laceration	6/3495 (0.2%)		5/3488 (0.1%)
Limb fracture	0/3495 (0%)		1/3488 (0%)
Lower limb fracture	3/3495 (0.1%)		4/3488 (0.1%)
Meniscus injury	3/3495 (0.1%)		2/3488 (0.1%)
Mouth injury	1/3495 (0%)		0/3488 (0%)
Multiple fractures	2/3495 (0.1%)		3/3488 (0.1%)
Multiple injuries	1/3495 (0%)		1/3488 (0%)
Muscle strain	0/3495 (0%)		1/3488 (0%)
Overdose	0/3495 (0%)		3/3488 (0.1%)
Pelvic fracture	9/3495 (0.3%)		5/3488 (0.1%)
Periprosthetic fracture	0/3495 (0%)		1/3488 (0%)
Pocket erosion	3/3495 (0.1%)		4/3488 (0.1%)
Post-traumatic pain	0/3495 (0%)		1/3488 (0%)
Postoperative ileus	2/3495 (0.1%)		1/3488 (0%)
Postoperative respiratory failure	1/3495 (0%)		0/3488 (0%)
Procedural complication	2/3495 (0.1%)		1/3488 (0%)
Procedural haemorrhage	1/3495 (0%)		0/3488 (0%)
Procedural hypotension	0/3495 (0%)		1/3488 (0%)
Procedural pain	1/3495 (0%)		0/3488 (0%)
Procedural pneumothorax	1/3495 (0%)		0/3488 (0%)
Radiation proctitis	0/3495 (0%)		1/3488 (0%)
Radius fracture	2/3495 (0.1%)		0/3488 (0%)
Rectal laceration postoperative	0/3495 (0%)		1/3488 (0%)
Rib fracture	4/3495 (0.1%)		3/3488 (0.1%)
Road traffic accident	3/3495 (0.1%)		0/3488 (0%)
Sacroiliac fracture	0/3495 (0%)		1/3488 (0%)
Scar	1/3495 (0%)		0/3488 (0%)
Scrotal haematoma	1/3495 (0%)		0/3488 (0%)
Sedation complication	1/3495 (0%)		0/3488 (0%)
Skin scar contracture	1/3495 (0%)		0/3488 (0%)
Spinal compression fracture	3/3495 (0.1%)		3/3488 (0.1%)
Splenic rupture	1/3495 (0%)		0/3488 (0%)
Subarachnoid haematoma	1/3495 (0%)		0/3488 (0%)
Subarachnoid haemorrhage	2/3495 (0.1%)		1/3488 (0%)
Subdural haematoma	12/3495 (0.3%)		11/3488 (0.3%)
Tendon rupture	1/3495 (0%)		1/3488 (0%)
Thoracic vertebral fracture	1/3495 (0%)		1/3488 (0%)
Tibia fracture	2/3495 (0.1%)		1/3488 (0%)
Toxicity to various agents	0/3495 (0%)		3/3488 (0.1%)
Twiddler's syndrome	3/3495 (0.1%)		0/3488 (0%)
Ulna fracture	0/3495 (0%)		2/3488 (0.1%)
Upper limb fracture	1/3495 (0%)		1/3488 (0%)
Urinary tract stoma complication	1/3495 (0%)		0/3488 (0%)
Vascular access site dissection	1/3495 (0%)		0/3488 (0%)
Vascular pseudoaneurysm	1/3495 (0%)		0/3488 (0%)
Vena cava injury	1/3495 (0%)		0/3488 (0%)
Wound	1/3495 (0%)		1/3488 (0%)
Wound dehiscence	2/3495 (0.1%)		0/3488 (0%)
Wrist fracture	1/3495 (0%)		0/3488 (0%)
Investigations
Anticoagulation drug level above therapeutic	2/3495 (0.1%)		1/3488 (0%)
Anticoagulation drug level below therapeutic	1/3495 (0%)		1/3488 (0%)
Blood glucose decreased	1/3495 (0%)		0/3488 (0%)
Blood potassium increased	1/3495 (0%)		0/3488 (0%)
Blood pressure increased	1/3495 (0%)		0/3488 (0%)
Cardiac output decreased	1/3495 (0%)		0/3488 (0%)
Colonoscopy	0/3495 (0%)		1/3488 (0%)
Ejection fraction decreased	0/3495 (0%)		1/3488 (0%)
Electrocardiogram T wave inversion	0/3495 (0%)		1/3488 (0%)
Femoral bruit	1/3495 (0%)		0/3488 (0%)
Haemoglobin decreased	0/3495 (0%)		3/3488 (0.1%)
Heart rate irregular	0/3495 (0%)		1/3488 (0%)
Hepatic enzyme increased	2/3495 (0.1%)		0/3488 (0%)
Influenza A virus test positive	0/3495 (0%)		2/3488 (0.1%)
International normalised ratio fluctuation	1/3495 (0%)		0/3488 (0%)
Platelet count decreased	0/3495 (0%)		1/3488 (0%)
Prothrombin time prolonged	0/3495 (0%)		1/3488 (0%)
Pulse absent	0/3495 (0%)		1/3488 (0%)
Transaminases increased	0/3495 (0%)		1/3488 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/3495 (0%)		1/3488 (0%)
Dehydration	10/3495 (0.3%)		12/3488 (0.3%)
Diabetes mellitus	2/3495 (0.1%)		2/3488 (0.1%)
Diabetes mellitus inadequate control	1/3495 (0%)		2/3488 (0.1%)
Diabetic ketoacidosis	2/3495 (0.1%)		2/3488 (0.1%)
Electrolyte imbalance	2/3495 (0.1%)		0/3488 (0%)
Failure to thrive	3/3495 (0.1%)		3/3488 (0.1%)
Fluid overload	3/3495 (0.1%)		3/3488 (0.1%)
Gout	4/3495 (0.1%)		4/3488 (0.1%)
Hypercalcaemia	0/3495 (0%)		1/3488 (0%)
Hyperglycaemia	6/3495 (0.2%)		3/3488 (0.1%)
Hyperkalaemia	1/3495 (0%)		8/3488 (0.2%)
Hypervolaemia	0/3495 (0%)		3/3488 (0.1%)
Hypoglycaemia	9/3495 (0.3%)		7/3488 (0.2%)
Hypokalaemia	4/3495 (0.1%)		4/3488 (0.1%)
Hypomagnesaemia	1/3495 (0%)		1/3488 (0%)
Hyponatraemia	8/3495 (0.2%)		3/3488 (0.1%)
Hypovolaemia	0/3495 (0%)		2/3488 (0.1%)
Lactic acidosis	1/3495 (0%)		0/3488 (0%)
Malnutrition	1/3495 (0%)		2/3488 (0.1%)
Obesity	5/3495 (0.1%)		3/3488 (0.1%)
Type 2 diabetes mellitus	0/3495 (0%)		1/3488 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/3495 (0.3%)		11/3488 (0.3%)
Arthritis	8/3495 (0.2%)		3/3488 (0.1%)
Arthropathy	1/3495 (0%)		0/3488 (0%)
Back pain	6/3495 (0.2%)		5/3488 (0.1%)
Bursitis	3/3495 (0.1%)		4/3488 (0.1%)
Chondropathy	1/3495 (0%)		0/3488 (0%)
Compartment syndrome	0/3495 (0%)		1/3488 (0%)
Dupuytren's contracture	1/3495 (0%)		0/3488 (0%)
Facial asymmetry	0/3495 (0%)		1/3488 (0%)
Foot deformity	2/3495 (0.1%)		0/3488 (0%)
Fracture nonunion	0/3495 (0%)		2/3488 (0.1%)
Gouty arthritis	0/3495 (0%)		2/3488 (0.1%)
Intervertebral disc degeneration	1/3495 (0%)		2/3488 (0.1%)
Intervertebral disc protrusion	3/3495 (0.1%)		0/3488 (0%)
Joint contracture	1/3495 (0%)		0/3488 (0%)
Joint stiffness	0/3495 (0%)		1/3488 (0%)
Lumbar spinal stenosis	4/3495 (0.1%)		2/3488 (0.1%)
Muscular weakness	0/3495 (0%)		2/3488 (0.1%)
Musculoskeletal chest pain	1/3495 (0%)		1/3488 (0%)
Musculoskeletal pain	5/3495 (0.1%)		1/3488 (0%)
Neck pain	0/3495 (0%)		2/3488 (0.1%)
Osteitis	1/3495 (0%)		0/3488 (0%)
Osteoarthritis	34/3495 (1%)		46/3488 (1.3%)
Osteolysis	0/3495 (0%)		1/3488 (0%)
Osteonecrosis	1/3495 (0%)		1/3488 (0%)
Pain in extremity	3/3495 (0.1%)		0/3488 (0%)
Polymyalgia rheumatica	0/3495 (0%)		1/3488 (0%)
Rheumatoid arthritis	2/3495 (0.1%)		0/3488 (0%)
Rotator cuff syndrome	3/3495 (0.1%)		10/3488 (0.3%)
Spinal column stenosis	1/3495 (0%)		0/3488 (0%)
Spinal osteoarthritis	3/3495 (0.1%)		5/3488 (0.1%)
Spondylolisthesis	0/3495 (0%)		3/3488 (0.1%)
Tendonitis	1/3495 (0%)		0/3488 (0%)
Tenosynovitis	1/3495 (0%)		0/3488 (0%)
Torticollis	1/3495 (0%)		0/3488 (0%)
Trigger finger	3/3495 (0.1%)		0/3488 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	0/3495 (0%)		3/3488 (0.1%)
Adenocarcinoma of colon	1/3495 (0%)		2/3488 (0.1%)
B-cell lymphoma	3/3495 (0.1%)		1/3488 (0%)
B precursor type acute leukaemia	0/3495 (0%)		1/3488 (0%)
Basal cell carcinoma	4/3495 (0.1%)		12/3488 (0.3%)
Benign neoplasm of bladder	0/3495 (0%)		1/3488 (0%)
Benign neoplasm of prostate	0/3495 (0%)		1/3488 (0%)
Benign renal neoplasm	0/3495 (0%)		1/3488 (0%)
Bile duct adenocarcinoma	1/3495 (0%)		0/3488 (0%)
Bile duct cancer	0/3495 (0%)		1/3488 (0%)
Bladder cancer	2/3495 (0.1%)		4/3488 (0.1%)
Bladder cancer recurrent	0/3495 (0%)		1/3488 (0%)
Bladder neoplasm	2/3495 (0.1%)		3/3488 (0.1%)
Bladder transitional cell carcinoma	0/3495 (0%)		1/3488 (0%)
Bladder transitional cell carcinoma recurrent	1/3495 (0%)		0/3488 (0%)
Bone cancer	0/3495 (0%)		1/3488 (0%)
Bowen's disease	0/3495 (0%)		1/3488 (0%)
Brain neoplasm	1/3495 (0%)		0/3488 (0%)
Breast cancer	6/3495 (0.2%)		4/3488 (0.1%)
Breast cancer metastatic	1/3495 (0%)		0/3488 (0%)
Cholangiocarcinoma	1/3495 (0%)		2/3488 (0.1%)
Cholesteatoma	1/3495 (0%)		0/3488 (0%)
Colon adenoma	1/3495 (0%)		1/3488 (0%)
Colon cancer	3/3495 (0.1%)		3/3488 (0.1%)
Colon cancer recurrent	0/3495 (0%)		1/3488 (0%)
Colorectal adenocarcinoma	1/3495 (0%)		0/3488 (0%)
Colorectal cancer	1/3495 (0%)		0/3488 (0%)
Endometrial adenocarcinoma	1/3495 (0%)		0/3488 (0%)
Gallbladder cancer	1/3495 (0%)		0/3488 (0%)
Gastric cancer	0/3495 (0%)		1/3488 (0%)
Gastrointestinal stromal tumour	1/3495 (0%)		0/3488 (0%)
Glioblastoma	0/3495 (0%)		1/3488 (0%)
Haemangioma of liver	0/3495 (0%)		1/3488 (0%)
Hepatic cancer	1/3495 (0%)		0/3488 (0%)
Hepatocellular carcinoma	0/3495 (0%)		1/3488 (0%)
Hodgkin's disease	1/3495 (0%)		0/3488 (0%)
Laryngeal cancer	1/3495 (0%)		0/3488 (0%)
Lip neoplasm malignant stage unspecified	1/3495 (0%)		0/3488 (0%)
Lipoma	0/3495 (0%)		1/3488 (0%)
Lung adenocarcinoma	2/3495 (0.1%)		3/3488 (0.1%)
Lung cancer metastatic	1/3495 (0%)		0/3488 (0%)
Lung carcinoma cell type unspecified recurrent	0/3495 (0%)		1/3488 (0%)
Lung neoplasm	1/3495 (0%)		1/3488 (0%)
Lung neoplasm malignant	3/3495 (0.1%)		4/3488 (0.1%)
Lung squamous cell carcinoma stage IV	0/3495 (0%)		1/3488 (0%)
Lymphoma	1/3495 (0%)		0/3488 (0%)
Malignant melanoma	3/3495 (0.1%)		2/3488 (0.1%)
Malignant melanoma in situ	0/3495 (0%)		1/3488 (0%)
Malignant neoplasm of ampulla of Vater	1/3495 (0%)		0/3488 (0%)
Malignant pleural effusion	0/3495 (0%)		1/3488 (0%)
Meningioma	0/3495 (0%)		1/3488 (0%)
Metastases to bone	0/3495 (0%)		1/3488 (0%)
Metastatic neoplasm	2/3495 (0.1%)		1/3488 (0%)
Metastatic renal cell carcinoma	0/3495 (0%)		1/3488 (0%)
Metastatic squamous cell carcinoma	0/3495 (0%)		1/3488 (0%)
Myelodysplastic syndrome	2/3495 (0.1%)		0/3488 (0%)
Nasal neoplasm	1/3495 (0%)		0/3488 (0%)
Nasopharyngeal cancer	1/3495 (0%)		0/3488 (0%)
Neoplasm	1/3495 (0%)		1/3488 (0%)
Neoplasm malignant	4/3495 (0.1%)		2/3488 (0.1%)
Neoplasm skin	0/3495 (0%)		1/3488 (0%)
Neurilemmoma benign	0/3495 (0%)		1/3488 (0%)
Neuroendocrine carcinoma	2/3495 (0.1%)		0/3488 (0%)
Non-Hodgkin's lymphoma	2/3495 (0.1%)		4/3488 (0.1%)
Non-small cell lung cancer	1/3495 (0%)		2/3488 (0.1%)
Non-small cell lung cancer metastatic	1/3495 (0%)		0/3488 (0%)
Oesophageal adenocarcinoma	1/3495 (0%)		2/3488 (0.1%)
Oesophageal cancer metastatic	0/3495 (0%)		1/3488 (0%)
Oesophageal carcinoma	0/3495 (0%)		1/3488 (0%)
Ovarian cancer metastatic	0/3495 (0%)		1/3488 (0%)
Pancreatic carcinoma	5/3495 (0.1%)		0/3488 (0%)
Pancreatic carcinoma metastatic	0/3495 (0%)		1/3488 (0%)
Papillary thyroid cancer	1/3495 (0%)		0/3488 (0%)
Parathyroid tumour benign	0/3495 (0%)		1/3488 (0%)
Prostate cancer	11/3495 (0.3%)		7/3488 (0.2%)
Prostate cancer metastatic	2/3495 (0.1%)		4/3488 (0.1%)
Rectal adenocarcinoma	1/3495 (0%)		1/3488 (0%)
Rectal cancer	1/3495 (0%)		0/3488 (0%)
Rectal cancer metastatic	1/3495 (0%)		0/3488 (0%)
Renal cancer	0/3495 (0%)		1/3488 (0%)
Renal cell carcinoma	1/3495 (0%)		2/3488 (0.1%)
Renal cell carcinoma stage II	0/3495 (0%)		1/3488 (0%)
Salivary gland neoplasm	0/3495 (0%)		1/3488 (0%)
Sarcoma metastatic	0/3495 (0%)		1/3488 (0%)
Skin cancer	2/3495 (0.1%)		5/3488 (0.1%)
Small cell lung cancer metastatic	1/3495 (0%)		0/3488 (0%)
Squamous cell carcinoma	4/3495 (0.1%)		2/3488 (0.1%)
Squamous cell carcinoma of lung	0/3495 (0%)		2/3488 (0.1%)
Squamous cell carcinoma of skin	0/3495 (0%)		5/3488 (0.1%)
T-cell lymphoma	1/3495 (0%)		0/3488 (0%)
Testis cancer	0/3495 (0%)		1/3488 (0%)
Throat cancer	0/3495 (0%)		1/3488 (0%)
Tongue neoplasm malignant stage unspecified	2/3495 (0.1%)		0/3488 (0%)
Transitional cell cancer of the renal pelvis and ureter	0/3495 (0%)		1/3488 (0%)
Transitional cell carcinoma	2/3495 (0.1%)		1/3488 (0%)
Ureteral neoplasm	0/3495 (0%)		1/3488 (0%)
Ureteric cancer	0/3495 (0%)		1/3488 (0%)
Uterine cancer	1/3495 (0%)		0/3488 (0%)
Vulval cancer stage 0	1/3495 (0%)		0/3488 (0%)
Nervous system disorders
Altered state of consciousness	0/3495 (0%)		1/3488 (0%)
Amnesia	1/3495 (0%)		1/3488 (0%)
Aphasia	1/3495 (0%)		1/3488 (0%)
Ataxia	1/3495 (0%)		2/3488 (0.1%)
Autonomic nervous system imbalance	1/3495 (0%)		0/3488 (0%)
Brain injury	1/3495 (0%)		0/3488 (0%)
Carotid artery disease	0/3495 (0%)		1/3488 (0%)
Carotid artery occlusion	2/3495 (0.1%)		1/3488 (0%)
Carotid artery stenosis	5/3495 (0.1%)		4/3488 (0.1%)
Carpal tunnel syndrome	3/3495 (0.1%)		3/3488 (0.1%)
Cerebral artery occlusion	1/3495 (0%)		0/3488 (0%)
Cerebral haemorrhage	2/3495 (0.1%)		4/3488 (0.1%)
Cerebral infarction	2/3495 (0.1%)		3/3488 (0.1%)
Cerebrovascular accident	34/3495 (1%)		26/3488 (0.7%)
Cognitive disorder	0/3495 (0%)		1/3488 (0%)
Dementia	5/3495 (0.1%)		2/3488 (0.1%)
Dementia Alzheimer's type	3/3495 (0.1%)		1/3488 (0%)
Dementia with Lewy bodies	0/3495 (0%)		1/3488 (0%)
Diabetic neuropathy	0/3495 (0%)		1/3488 (0%)
Dizziness	6/3495 (0.2%)		8/3488 (0.2%)
Dizziness postural	0/3495 (0%)		2/3488 (0.1%)
Dysarthria	1/3495 (0%)		1/3488 (0%)
Embolic stroke	0/3495 (0%)		2/3488 (0.1%)
Encephalopathy	4/3495 (0.1%)		4/3488 (0.1%)
Facial paralysis	0/3495 (0%)		1/3488 (0%)
Focal dyscognitive seizures	0/3495 (0%)		1/3488 (0%)
Haemorrhage intracranial	5/3495 (0.1%)		1/3488 (0%)
Haemorrhagic stroke	2/3495 (0.1%)		1/3488 (0%)
Headache	5/3495 (0.1%)		2/3488 (0.1%)
Hemiparesis	1/3495 (0%)		0/3488 (0%)
Hemiplegia	1/3495 (0%)		0/3488 (0%)
Hemiplegic migraine	0/3495 (0%)		1/3488 (0%)
Hepatic encephalopathy	0/3495 (0%)		2/3488 (0.1%)
Hydrocephalus	1/3495 (0%)		0/3488 (0%)
Hypoaesthesia	0/3495 (0%)		1/3488 (0%)
Intracranial mass	1/3495 (0%)		1/3488 (0%)
Intracranial pressure increased	0/3495 (0%)		1/3488 (0%)
Intraneural cyst	0/3495 (0%)		1/3488 (0%)
Ischaemic stroke	2/3495 (0.1%)		11/3488 (0.3%)
Lacunar infarction	1/3495 (0%)		0/3488 (0%)
Lacunar stroke	0/3495 (0%)		1/3488 (0%)
Loss of consciousness	3/3495 (0.1%)		1/3488 (0%)
Lumbar radiculopathy	2/3495 (0.1%)		0/3488 (0%)
Metabolic encephalopathy	4/3495 (0.1%)		1/3488 (0%)
Migraine	1/3495 (0%)		0/3488 (0%)
Myelomalacia	1/3495 (0%)		0/3488 (0%)
Myelopathy	1/3495 (0%)		0/3488 (0%)
Neurodegenerative disorder	0/3495 (0%)		1/3488 (0%)
Paraesthesia	1/3495 (0%)		0/3488 (0%)
Parkinson's disease	0/3495 (0%)		2/3488 (0.1%)
Peroneal nerve palsy	1/3495 (0%)		0/3488 (0%)
Polyneuropathy alcoholic	1/3495 (0%)		0/3488 (0%)
Post herpetic neuralgia	0/3495 (0%)		1/3488 (0%)
Presyncope	2/3495 (0.1%)		4/3488 (0.1%)
Restless legs syndrome	1/3495 (0%)		0/3488 (0%)
Sciatica	2/3495 (0.1%)		0/3488 (0%)
Seizure	3/3495 (0.1%)		4/3488 (0.1%)
Seizure like phenomena	0/3495 (0%)		1/3488 (0%)
Syncope	24/3495 (0.7%)		28/3488 (0.8%)
Thalamic infarction	0/3495 (0%)		1/3488 (0%)
Transient ischaemic attack	26/3495 (0.7%)		16/3488 (0.5%)
Tremor	0/3495 (0%)		2/3488 (0.1%)
Trigeminal neuralgia	0/3495 (0%)		1/3488 (0%)
Unresponsive to stimuli	0/3495 (0%)		1/3488 (0%)
VIth nerve paralysis	1/3495 (0%)		0/3488 (0%)
Pregnancy, puerperium and perinatal conditions
Delivery	0/3495 (0%)		1/3488 (0%)
Pregnancy	1/3495 (0%)		0/3488 (0%)
Product Issues
Device battery issue	3/3495 (0.1%)		1/3488 (0%)
Device breakage	0/3495 (0%)		1/3488 (0%)
Device capturing issue	9/3495 (0.3%)		9/3488 (0.3%)
Device connection issue	0/3495 (0%)		1/3488 (0%)
Device dislocation	3/3495 (0.1%)		4/3488 (0.1%)
Device electrical impedance issue	5/3495 (0.1%)		6/3488 (0.2%)
Device end of service	0/3495 (0%)		1/3488 (0%)
Device extrusion	1/3495 (0%)		5/3488 (0.1%)
Device failure	0/3495 (0%)		2/3488 (0.1%)
Device inappropriate shock delivery	6/3495 (0.2%)		11/3488 (0.3%)
Device lead damage	19/3495 (0.5%)		24/3488 (0.7%)
Device lead issue	7/3495 (0.2%)		11/3488 (0.3%)
Device loosening	0/3495 (0%)		1/3488 (0%)
Device malfunction	10/3495 (0.3%)		14/3488 (0.4%)
Device pacing issue	16/3495 (0.5%)		6/3488 (0.2%)
Device stimulation issue	11/3495 (0.3%)		20/3488 (0.6%)
Implant subsidence	0/3495 (0%)		1/3488 (0%)
Lead dislodgement	39/3495 (1.1%)		37/3488 (1.1%)
Oversensing	1/3495 (0%)		10/3488 (0.3%)
Thrombosis in device	1/3495 (0%)		0/3488 (0%)
Undersensing	1/3495 (0%)		1/3488 (0%)
Psychiatric disorders
Alcohol abuse	1/3495 (0%)		0/3488 (0%)
Bipolar disorder	1/3495 (0%)		0/3488 (0%)
Bipolar I disorder	1/3495 (0%)		0/3488 (0%)
Confusional state	0/3495 (0%)		2/3488 (0.1%)
Delirium	1/3495 (0%)		2/3488 (0.1%)
Depression	1/3495 (0%)		1/3488 (0%)
Hallucination, visual	0/3495 (0%)		1/3488 (0%)
Intentional self-injury	1/3495 (0%)		0/3488 (0%)
Mental status changes	9/3495 (0.3%)		9/3488 (0.3%)
Psychotic disorder	0/3495 (0%)		1/3488 (0%)
Schizoaffective disorder	0/3495 (0%)		1/3488 (0%)
Substance-induced psychotic disorder	0/3495 (0%)		1/3488 (0%)
Suicidal behaviour	1/3495 (0%)		0/3488 (0%)
Suicidal ideation	0/3495 (0%)		2/3488 (0.1%)
Suicide attempt	0/3495 (0%)		1/3488 (0%)
Renal and urinary disorders
Acute kidney injury	66/3495 (1.9%)		72/3488 (2.1%)
Bladder neck obstruction	0/3495 (0%)		1/3488 (0%)
Bladder outlet obstruction	1/3495 (0%)		1/3488 (0%)
Calculus bladder	3/3495 (0.1%)		0/3488 (0%)
Calculus urethral	0/3495 (0%)		1/3488 (0%)
Calculus urinary	0/3495 (0%)		1/3488 (0%)
Chronic kidney disease	3/3495 (0.1%)		7/3488 (0.2%)
End stage renal disease	3/3495 (0.1%)		5/3488 (0.1%)
Haematuria	4/3495 (0.1%)		5/3488 (0.1%)
Hydronephrosis	2/3495 (0.1%)		1/3488 (0%)
Myeloma cast nephropathy	0/3495 (0%)		1/3488 (0%)
Nephrolithiasis	5/3495 (0.1%)		5/3488 (0.1%)
Nephropathy	1/3495 (0%)		0/3488 (0%)
Nephropathy toxic	0/3495 (0%)		1/3488 (0%)
Nephrotic syndrome	0/3495 (0%)		1/3488 (0%)
Pulmonary renal syndrome	1/3495 (0%)		0/3488 (0%)
Renal aneurysm	0/3495 (0%)		1/3488 (0%)
Renal artery stenosis	1/3495 (0%)		0/3488 (0%)
Renal embolism	1/3495 (0%)		0/3488 (0%)
Renal failure	8/3495 (0.2%)		11/3488 (0.3%)
Renal haematoma	1/3495 (0%)		0/3488 (0%)
Renal impairment	0/3495 (0%)		2/3488 (0.1%)
Renal mass	1/3495 (0%)		1/3488 (0%)
Tubulointerstitial nephritis	1/3495 (0%)		0/3488 (0%)
Ureterolithiasis	4/3495 (0.1%)		6/3488 (0.2%)
Urethral disorder	0/3495 (0%)		1/3488 (0%)
Urethral stenosis	1/3495 (0%)		0/3488 (0%)
Urinary bladder polyp	2/3495 (0.1%)		0/3488 (0%)
Urinary retention	5/3495 (0.1%)		7/3488 (0.2%)
Urinary tract obstruction	2/3495 (0.1%)		1/3488 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	9/3495 (0.3%)		7/3488 (0.2%)
Breast mass	0/3495 (0%)		1/3488 (0%)
Cervical dysplasia	1/3495 (0%)		0/3488 (0%)
Dysfunctional uterine bleeding	0/3495 (0%)		1/3488 (0%)
Ovarian cyst	1/3495 (0%)		0/3488 (0%)
Pelvic pain	1/3495 (0%)		0/3488 (0%)
Prostatic haemorrhage	1/3495 (0%)		0/3488 (0%)
Prostatitis	0/3495 (0%)		1/3488 (0%)
Prostatomegaly	1/3495 (0%)		0/3488 (0%)
Rectoprostatic fistula	1/3495 (0%)		0/3488 (0%)
Uterine polyp	2/3495 (0.1%)		0/3488 (0%)
Vaginal haemorrhage	1/3495 (0%)		0/3488 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	2/3495 (0.1%)		0/3488 (0%)
Acute respiratory distress syndrome	1/3495 (0%)		2/3488 (0.1%)
Acute respiratory failure	12/3495 (0.3%)		22/3488 (0.6%)
Asthma	0/3495 (0%)		2/3488 (0.1%)
Atelectasis	3/3495 (0.1%)		2/3488 (0.1%)
Bronchial disorder	0/3495 (0%)		1/3488 (0%)
Bronchial hyperreactivity	1/3495 (0%)		1/3488 (0%)
Bronchitis chronic	1/3495 (0%)		0/3488 (0%)
Bronchopneumopathy	0/3495 (0%)		1/3488 (0%)
Chronic obstructive pulmonary disease	45/3495 (1.3%)		32/3488 (0.9%)
Chronic respiratory failure	0/3495 (0%)		1/3488 (0%)
Cough	1/3495 (0%)		0/3488 (0%)
Dyspnoea	22/3495 (0.6%)		18/3488 (0.5%)
Dyspnoea exertional	2/3495 (0.1%)		3/3488 (0.1%)
Epistaxis	4/3495 (0.1%)		3/3488 (0.1%)
Haemoptysis	0/3495 (0%)		2/3488 (0.1%)
Haemothorax	0/3495 (0%)		1/3488 (0%)
Hypoxia	1/3495 (0%)		0/3488 (0%)
Idiopathic pulmonary fibrosis	1/3495 (0%)		0/3488 (0%)
Interstitial lung disease	1/3495 (0%)		1/3488 (0%)
Lung disorder	1/3495 (0%)		0/3488 (0%)
Lung infiltration	1/3495 (0%)		0/3488 (0%)
Mediastinal haematoma	0/3495 (0%)		1/3488 (0%)
Nasal septum perforation	1/3495 (0%)		0/3488 (0%)
Pharyngeal haemorrhage	0/3495 (0%)		1/3488 (0%)
Pleural effusion	16/3495 (0.5%)		11/3488 (0.3%)
Pneumonia aspiration	7/3495 (0.2%)		10/3488 (0.3%)
Pneumonitis	0/3495 (0%)		1/3488 (0%)
Pneumothorax	9/3495 (0.3%)		11/3488 (0.3%)
Pulmonary cavitation	0/3495 (0%)		1/3488 (0%)
Pulmonary congestion	1/3495 (0%)		1/3488 (0%)
Pulmonary embolism	11/3495 (0.3%)		3/3488 (0.1%)
Pulmonary fibrosis	1/3495 (0%)		0/3488 (0%)
Pulmonary granuloma	0/3495 (0%)		1/3488 (0%)
Pulmonary hypertension	1/3495 (0%)		1/3488 (0%)
Pulmonary mass	2/3495 (0.1%)		6/3488 (0.2%)
Pulmonary oedema	9/3495 (0.3%)		5/3488 (0.1%)
Pulmonary sarcoidosis	1/3495 (0%)		0/3488 (0%)
Pulmonary toxicity	2/3495 (0.1%)		0/3488 (0%)
Respiratory arrest	0/3495 (0%)		1/3488 (0%)
Respiratory distress	3/3495 (0.1%)		1/3488 (0%)
Respiratory failure	30/3495 (0.9%)		32/3488 (0.9%)
Respiratory tract congestion	1/3495 (0%)		0/3488 (0%)
Sleep apnoea syndrome	1/3495 (0%)		0/3488 (0%)
Tracheal mass	0/3495 (0%)		1/3488 (0%)
Tracheomalacia	1/3495 (0%)		0/3488 (0%)
Upper respiratory tract congestion	0/3495 (0%)		1/3488 (0%)
Wheezing	1/3495 (0%)		0/3488 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/3495 (0%)		2/3488 (0.1%)
Brow ptosis	0/3495 (0%)		1/3488 (0%)
Decubitus ulcer	3/3495 (0.1%)		2/3488 (0.1%)
Dermal cyst	1/3495 (0%)		0/3488 (0%)
Dermatitis allergic	1/3495 (0%)		0/3488 (0%)
Dermatitis contact	1/3495 (0%)		0/3488 (0%)
Diabetic foot	0/3495 (0%)		2/3488 (0.1%)
Hidradenitis	1/3495 (0%)		0/3488 (0%)
Ischaemic skin ulcer	0/3495 (0%)		1/3488 (0%)
Rash generalised	1/3495 (0%)		0/3488 (0%)
Skin lesion	0/3495 (0%)		1/3488 (0%)
Skin ulcer	4/3495 (0.1%)		7/3488 (0.2%)
Stasis dermatitis	0/3495 (0%)		2/3488 (0.1%)
Urticaria	0/3495 (0%)		1/3488 (0%)
Vasculitic rash	0/3495 (0%)		1/3488 (0%)
Social circumstances
Elderly	1/3495 (0%)		0/3488 (0%)
Familial risk factor	1/3495 (0%)		0/3488 (0%)
Surgical and medical procedures
Argon plasma coagulation	0/3495 (0%)		1/3488 (0%)
Arteriovenous fistula operation	1/3495 (0%)		0/3488 (0%)
Blepharoplasty	1/3495 (0%)		0/3488 (0%)
Cataract operation	1/3495 (0%)		1/3488 (0%)
Coronary artery bypass	1/3495 (0%)		0/3488 (0%)
Heart transplant	0/3495 (0%)		1/3488 (0%)
Hernia repair	2/3495 (0.1%)		0/3488 (0%)
Hip arthroplasty	1/3495 (0%)		0/3488 (0%)
Inguinal hernia repair	1/3495 (0%)		1/3488 (0%)
Jejunostomy	1/3495 (0%)		0/3488 (0%)
Leg amputation	1/3495 (0%)		0/3488 (0%)
Metatarsal excision	0/3495 (0%)		1/3488 (0%)
Mitral valve replacement	1/3495 (0%)		0/3488 (0%)
Neurectomy	1/3495 (0%)		0/3488 (0%)
Prostatectomy	0/3495 (0%)		1/3488 (0%)
Wound treatment	0/3495 (0%)		1/3488 (0%)
Vascular disorders
Accelerated hypertension	1/3495 (0%)		0/3488 (0%)
Aneurysm ruptured	1/3495 (0%)		1/3488 (0%)
Aortic aneurysm	8/3495 (0.2%)		7/3488 (0.2%)
Aortic dissection	2/3495 (0.1%)		3/3488 (0.1%)
Aortic rupture	1/3495 (0%)		0/3488 (0%)
Aortic stenosis	8/3495 (0.2%)		16/3488 (0.5%)
Arterial disorder	1/3495 (0%)		0/3488 (0%)
Arterial occlusive disease	1/3495 (0%)		0/3488 (0%)
Arteriosclerosis	1/3495 (0%)		5/3488 (0.1%)
Bleeding varicose vein	0/3495 (0%)		1/3488 (0%)
Blood pressure fluctuation	0/3495 (0%)		1/3488 (0%)
Brachiocephalic artery occlusion	0/3495 (0%)		1/3488 (0%)
Brachiocephalic vein occlusion	0/3495 (0%)		1/3488 (0%)
Brachiocephalic vein stenosis	0/3495 (0%)		1/3488 (0%)
Deep vein thrombosis	13/3495 (0.4%)		13/3488 (0.4%)
Haematoma	8/3495 (0.2%)		3/3488 (0.1%)
Haemorrhage	0/3495 (0%)		1/3488 (0%)
Hypertension	0/3495 (0%)		1/3488 (0%)
Hypertensive crisis	2/3495 (0.1%)		1/3488 (0%)
Hypertensive emergency	3/3495 (0.1%)		0/3488 (0%)
Hypotension	15/3495 (0.4%)		16/3488 (0.5%)
Hypovolaemic shock	1/3495 (0%)		1/3488 (0%)
Intermittent claudication	3/3495 (0.1%)		1/3488 (0%)
Ischaemia	1/3495 (0%)		2/3488 (0.1%)
Jugular vein thrombosis	0/3495 (0%)		1/3488 (0%)
Lymphoedema	2/3495 (0.1%)		0/3488 (0%)
Orthostatic hypotension	5/3495 (0.1%)		5/3488 (0.1%)
Peripheral arterial occlusive disease	7/3495 (0.2%)		6/3488 (0.2%)
Peripheral artery occlusion	2/3495 (0.1%)		1/3488 (0%)
Peripheral artery stenosis	0/3495 (0%)		3/3488 (0.1%)
Peripheral artery thrombosis	1/3495 (0%)		1/3488 (0%)
Peripheral embolism	1/3495 (0%)		0/3488 (0%)
Peripheral ischaemia	9/3495 (0.3%)		9/3488 (0.3%)
Peripheral vascular disorder	5/3495 (0.1%)		6/3488 (0.2%)
Peripheral venous disease	1/3495 (0%)		1/3488 (0%)
Shock haemorrhagic	3/3495 (0.1%)		2/3488 (0.1%)
Subclavian vein occlusion	0/3495 (0%)		2/3488 (0.1%)
Subclavian vein stenosis	0/3495 (0%)		1/3488 (0%)
Subclavian vein thrombosis	1/3495 (0%)		0/3488 (0%)
Superior vena cava syndrome	1/3495 (0%)		0/3488 (0%)
Thrombophlebitis	2/3495 (0.1%)		0/3488 (0%)
Thrombosis	3/3495 (0.1%)		0/3488 (0%)
Varicose vein	1/3495 (0%)		1/3488 (0%)
Vasculitis	0/3495 (0%)		1/3488 (0%)
Vena cava embolism	0/3495 (0%)		1/3488 (0%)
Venous occlusion	8/3495 (0.2%)		3/3488 (0.1%)
Venous stenosis	0/3495 (0%)		1/3488 (0%)
Venous thrombosis limb	2/3495 (0.1%)		4/3488 (0.1%)
Other (Not Including Serious) Adverse Events
	TYRX Envelope		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	286/3495 (8.2%)		221/3488 (6.3%)
Blood and lymphatic system disorders
Anaemia macrocytic	1/3495 (0%)		0/3488 (0%)
Cardiac disorders
Angina pectoris	1/3495 (0%)		0/3488 (0%)
Arrhythmia supraventricular	1/3495 (0%)		0/3488 (0%)
Atrial fibrillation	1/3495 (0%)		2/3488 (0.1%)
Atrioventricular block	1/3495 (0%)		0/3488 (0%)
Cardiac discomfort	1/3495 (0%)		0/3488 (0%)
Cardiac failure	1/3495 (0%)		1/3488 (0%)
Cardiac failure congestive	1/3495 (0%)		0/3488 (0%)
Intracardiac thrombus	1/3495 (0%)		0/3488 (0%)
Palpitations	1/3495 (0%)		0/3488 (0%)
Pericardial effusion	0/3495 (0%)		1/3488 (0%)
Pericarditis	1/3495 (0%)		0/3488 (0%)
Ventricular fibrillation	1/3495 (0%)		0/3488 (0%)
Ventricular tachycardia	1/3495 (0%)		1/3488 (0%)
Gastrointestinal disorders
Abdominal pain upper	1/3495 (0%)		0/3488 (0%)
Diarrhoea	1/3495 (0%)		0/3488 (0%)
Nausea	2/3495 (0.1%)		0/3488 (0%)
Pancreatitis	1/3495 (0%)		0/3488 (0%)
Toothache	0/3495 (0%)		1/3488 (0%)
General disorders
Adverse drug reaction	1/3495 (0%)		0/3488 (0%)
Asthenia	1/3495 (0%)		0/3488 (0%)
Chest pain	1/3495 (0%)		3/3488 (0.1%)
Exercise tolerance decreased	0/3495 (0%)		1/3488 (0%)
Hernia	1/3495 (0%)		0/3488 (0%)
Impaired healing	3/3495 (0.1%)		1/3488 (0%)
Implant site bruising	7/3495 (0.2%)		2/3488 (0.1%)
Implant site dehiscence	4/3495 (0.1%)		3/3488 (0.1%)
Implant site discharge	3/3495 (0.1%)		0/3488 (0%)
Implant site erythema	4/3495 (0.1%)		4/3488 (0.1%)
Implant site extravasation	1/3495 (0%)		1/3488 (0%)
Implant site haematoma	56/3495 (1.6%)		43/3488 (1.2%)
Implant site haemorrhage	6/3495 (0.2%)		5/3488 (0.1%)
Implant site inflammation	1/3495 (0%)		0/3488 (0%)
Implant site irritation	4/3495 (0.1%)		2/3488 (0.1%)
Implant site oedema	1/3495 (0%)		1/3488 (0%)
Implant site pain	23/3495 (0.7%)		20/3488 (0.6%)
Implant site pruritus	3/3495 (0.1%)		2/3488 (0.1%)
Implant site rash	6/3495 (0.2%)		0/3488 (0%)
Implant site scar	1/3495 (0%)		0/3488 (0%)
Implant site swelling	13/3495 (0.4%)		10/3488 (0.3%)
Implant site vesicles	1/3495 (0%)		1/3488 (0%)
Medical device site laceration	0/3495 (0%)		1/3488 (0%)
Medical device site pain	1/3495 (0%)		0/3488 (0%)
Medical device site paraesthesia	0/3495 (0%)		1/3488 (0%)
Oedema peripheral	1/3495 (0%)		0/3488 (0%)
Pacemaker generated arrhythmia	1/3495 (0%)		0/3488 (0%)
Pacemaker syndrome	0/3495 (0%)		1/3488 (0%)
Peripheral swelling	1/3495 (0%)		1/3488 (0%)
Phantom shocks	4/3495 (0.1%)		2/3488 (0.1%)
Pyrexia	2/3495 (0.1%)		0/3488 (0%)
Immune system disorders
Drug hypersensitivity	1/3495 (0%)		0/3488 (0%)
Hypersensitivity	0/3495 (0%)		1/3488 (0%)
Infections and infestations
Cellulitis	1/3495 (0%)		0/3488 (0%)
Device related infection	1/3495 (0%)		2/3488 (0.1%)
Implant site cellulitis	2/3495 (0.1%)		2/3488 (0.1%)
Implant site infection	8/3495 (0.2%)		14/3488 (0.4%)
Infection	1/3495 (0%)		1/3488 (0%)
Infusion site cellulitis	1/3495 (0%)		0/3488 (0%)
Lower respiratory tract infection	1/3495 (0%)		0/3488 (0%)
Perichondritis	1/3495 (0%)		0/3488 (0%)
Pneumonia	0/3495 (0%)		5/3488 (0.1%)
Staphylococcal skin infection	1/3495 (0%)		0/3488 (0%)
Stitch abscess	3/3495 (0.1%)		1/3488 (0%)
Upper respiratory tract infection	1/3495 (0%)		0/3488 (0%)
Urinary tract infection	1/3495 (0%)		1/3488 (0%)
Wound infection	1/3495 (0%)		2/3488 (0.1%)
Injury, poisoning and procedural complications
Ankle fracture	0/3495 (0%)		1/3488 (0%)
Cardiac procedure complication	1/3495 (0%)		0/3488 (0%)
Cardiac vein dissection	0/3495 (0%)		1/3488 (0%)
Incision site complication	1/3495 (0%)		0/3488 (0%)
Incision site haematoma	2/3495 (0.1%)		5/3488 (0.1%)
Incision site haemorrhage	3/3495 (0.1%)		1/3488 (0%)
Incision site pain	0/3495 (0%)		1/3488 (0%)
Incision site pruritus	2/3495 (0.1%)		0/3488 (0%)
Incision site vesicles	1/3495 (0%)		0/3488 (0%)
Laceration	1/3495 (0%)		0/3488 (0%)
Post procedural contusion	1/3495 (0%)		0/3488 (0%)
Procedural anxiety	0/3495 (0%)		1/3488 (0%)
Procedural complication	0/3495 (0%)		1/3488 (0%)
Procedural hypotension	1/3495 (0%)		0/3488 (0%)
Suture related complication	1/3495 (0%)		0/3488 (0%)
Wound dehiscence	2/3495 (0.1%)		1/3488 (0%)
Investigations
Blood creatinine increased	1/3495 (0%)		0/3488 (0%)
Musculoskeletal and connective tissue disorders
Flank pain	1/3495 (0%)		0/3488 (0%)
Muscular weakness	1/3495 (0%)		0/3488 (0%)
Musculoskeletal chest pain	0/3495 (0%)		1/3488 (0%)
Musculoskeletal pain	1/3495 (0%)		2/3488 (0.1%)
Neck pain	0/3495 (0%)		1/3488 (0%)
Pain in extremity	1/3495 (0%)		0/3488 (0%)
Nervous system disorders
Presyncope	1/3495 (0%)		0/3488 (0%)
Syncope	1/3495 (0%)		1/3488 (0%)
Product Issues
Device capturing issue	4/3495 (0.1%)		3/3488 (0.1%)
Device dislocation	2/3495 (0.1%)		0/3488 (0%)
Device electrical finding	1/3495 (0%)		0/3488 (0%)
Device electrical impedance issue	7/3495 (0.2%)		4/3488 (0.1%)
Device inappropriate shock delivery	3/3495 (0.1%)		3/3488 (0.1%)
Device lead damage	1/3495 (0%)		1/3488 (0%)
Device lead issue	3/3495 (0.1%)		3/3488 (0.1%)
Device malfunction	1/3495 (0%)		0/3488 (0%)
Device pacing issue	7/3495 (0.2%)		9/3488 (0.3%)
Device signal detection issue	2/3495 (0.1%)		0/3488 (0%)
Device stimulation issue	44/3495 (1.3%)		37/3488 (1.1%)
Electromagnetic interference	1/3495 (0%)		0/3488 (0%)
Lead dislodgement	2/3495 (0.1%)		0/3488 (0%)
Oversensing	11/3495 (0.3%)		10/3488 (0.3%)
Undersensing	3/3495 (0.1%)		0/3488 (0%)
Renal and urinary disorders
Acute kidney injury	0/3495 (0%)		1/3488 (0%)
Reproductive system and breast disorders
Breast tenderness	1/3495 (0%)		0/3488 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/3495 (0.1%)		0/3488 (0%)
Pneumonia aspiration	0/3495 (0%)		1/3488 (0%)
Pneumothorax	2/3495 (0.1%)		0/3488 (0%)
Pulmonary vascular disorder	1/3495 (0%)		0/3488 (0%)
Respiratory failure	1/3495 (0%)		0/3488 (0%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	1/3495 (0%)		4/3488 (0.1%)
Ischaemic skin ulcer	1/3495 (0%)		0/3488 (0%)
Keloid scar	1/3495 (0%)		0/3488 (0%)
Pruritus	1/3495 (0%)		0/3488 (0%)
Rash	2/3495 (0.1%)		2/3488 (0.1%)
Skin discolouration	0/3495 (0%)		1/3488 (0%)
Vascular disorders
Deep vein thrombosis	3/3495 (0.1%)		2/3488 (0.1%)
Haematoma	1/3495 (0%)		0/3488 (0%)
Hypotension	1/3495 (0%)		1/3488 (0%)
Jugular vein thrombosis	1/3495 (0%)		0/3488 (0%)
Subclavian vein thrombosis	0/3495 (0%)		1/3488 (0%)
Thrombophlebitis	0/3495 (0%)		1/3488 (0%)
Thrombosis	1/3495 (0%)		2/3488 (0.1%)
Venous occlusion	1/3495 (0%)		0/3488 (0%)
Venous stenosis	1/3495 (0%)		0/3488 (0%)
Venous thrombosis limb	0/3495 (0%)		2/3488 (0.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

In most cases, the contract allows the principal investigator to publish their data after release of a multi-center publication per the publication strategy following Medtronic's review for disclosure of confidential information ("CI"), technical correctness, disclosure of patentable or copyrightable material, and selection and order of publications by the publications committee. Any such CI and/or item identified as not technically correct is deleted prior to publication/presentation.

Results Point of Contact

Name/Title	Daniel Lexcen, Sr. Clinical Program Manager
Organization	Medtronic
Phone	+17635269702
Email	daniel.lexcen@medtronic.com

Responsible Party:

Medtronic Cardiac Rhythm and Heart Failure

ClinicalTrials.gov Identifier:

NCT02277990

Other Study ID Numbers:

WRAP-IT

First Posted:

Oct 29, 2014

Last Update Posted:

Nov 5, 2019

Last Verified:

Oct 1, 2019

WRAP-IT: World-wide Randomized Antibiotic Envelope Infection Prevention Trial

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact