Clinical trial NCT02277990: World-wide Randomized Antibiotic Envelope Infection Prevention Trial
Official title: Cardiac Implantable Electronic Device (CIED) Antibiotic Envelope Infection Prevention Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: CIED Related Infection
Lead sponsor: Medtronic Cardiac Rhythm and Heart Failure
Sponsor class: INDUSTRY
Collaborators: name: The Cleveland Clinic
First posted: 2014-10-29
Enrollment: 7075
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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:

  a. 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

  i. Subjects planned to have leads added, or extracted and added for upgrades can be enrolled OR

  b. Patient will undergo a de novo Medtronic CRT-D system implant per approved indications

OR

c. 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.

Primary outcomes:
measure: 12 Month Kaplan-Meier Estimate of Major CIED Infection Rate
timeFrame: Implant to 12 months
Secondary outcomes:
measure: 12 Month Kaplan-Meier Estimate of Major or Minor CIED Infection
timeFrame: Implant to 12 months
measure: 12 Month Kaplan-Meier Estimate of a CIED Procedure Related or System Related Complication
timeFrame: Implant to 12 months
measure: Kaplan-Meier Estimate of a Major Infection Throughout Follow-up
timeFrame: Throughout study follow-up Kaplan-Meier Estimate is at 36 Months
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Heart Institute
state: Alaska
city: Mesa
country: United States
facility: Tri-City Cardiology Consultants
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Arrhythmia Consultants
state: Arizona
city: Chula Vista
country: United States
facility: Chula Vista Cardiac Center
state: California
city: Fresno
country: United States
facility: Cardiovascular Consultants Heart Center
state: California
city: La Jolla
country: United States
facility: UCSD Medical Center
state: California
city: Rancho Mirage
country: United States
facility: Eisenhower Desert Cardiology Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco UCSF Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Hospital & Clinics
state: California
city: Stockton
country: United States
facility: Saint Joseph's Medical Center
state: California
city: Colorado Springs
country: United States
facility: Penrose St. Francis Hospital
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Lafayette
country: United States
facility: SCL Physicians Heart Institute of Colorado
state: Colorado
city: Danbury
country: United States
facility: Danbury Hospital
state: Connecticut
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Atlantis
country: United States
facility: Florida Electrophysiology Associates
state: Florida
city: Clearwater
country: United States
facility: Clearwater Cardiovascular & Interventional Consultants
state: Florida
city: Gainesville
country: United States
facility: The Cardiac & Vascular Institute
state: Florida
city: Gainesville
country: United States
facility: University of Florida Health Shands Hospital
state: Florida
city: Coeur d'Alene
country: United States
facility: Kootenai Heart Clinics Northwest
state: Idaho
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Springfield
country: United States
facility: Prairie Education & Research Cooperative (Springfield IL)
state: Illinois
city: Indianapolis
country: United States
facility: Saint Vincent Medical Group
state: Indiana
city: West Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Kansas City
country: United States
facility: The University Kansas Medical Center Research Institute Inc
state: Kansas
city: Lexington
country: United States
facility: Lexington Cardiac Research Foundation
state: Kentucky
city: Louisville
country: United States
facility: Norton Cardiovascular Associates
state: Kentucky
city: Baton Rouge
country: United States
facility: Cardiovascular Research Foundation of Louisiana
state: Louisiana
city: Shreveport
country: United States
facility: Advanced Cardiovascular Specialists
state: Louisiana
city: Scarborough
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Salisbury
country: United States
facility: Delmarva Heart Research Foundation Inc
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Lansing
country: United States
facility: Sparrow Clinical Research Institute
state: Michigan
city: Marquette
country: United States
facility: DLP Marquette Physicians Practices Inc
state: Michigan
city: Marquette
country: United States
facility: Upper Michigan Cardiovascular Associates PC
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Hospital - Royal Oak
state: Michigan
city: Saint Joseph
country: United States
facility: Great Lakes Heart and Vascular Institute PC
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Robbinsdale
country: United States
facility: North Memorial Heart and Vascular Institute
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Heart & Vascular Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Heart and Vascular Clinic
state: Minnesota
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic/ Forrest General
state: Mississippi
city: Kansas City
country: United States
facility: Mid America Heart Institute (MAHI)
state: Missouri
city: Saint Louis
country: United States
facility: Saint Anthonys Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Englewood
country: United States
facility: Englewood Hospital & Medical Center
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: Voorhees
country: United States
facility: Lourdes Cardiology Services
state: New Jersey
city: Liverpool
country: United States
facility: Saint Joseph's Hospital Health Center
state: New York
city: New York
country: United States
facility: Cornell University Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Saint Luke's Hospital
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: NYU
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Asheville
country: United States
facility: Asheville Cardiology Associate PA
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Heart and Vascular Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center (DUMC)
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Cardiology Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Forsyth Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences / Baptist Medical Center / North Carolina Baptist Hospital
state: North Carolina
city: Akron
country: United States
facility: Akron General Medical Center
state: Ohio
city: Akron
country: United States
facility: Northeast Ohio Cardiovascular Specialists
state: Ohio
city: Cincinnati
country: United States
facility: The Lindner Research Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Riverside Methodist Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Poland
country: United States
facility: Saint Elizabeth Health Center
state: Ohio
city: Westerville
country: United States
facility: Mount Carmel East
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Heart Hospital Research Foundation
state: Oklahoma
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Science Center (OUHSC)
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Portland
country: United States
facility: Legacy Medical Group
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University Hospital
state: Oregon
city: Portland
country: United States
facility: Providence Health & Services
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital Cedar Crest
state: Pennsylvania
city: Bethlehem
country: United States
facility: Saint Luke's Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Doylestown
country: United States
facility: Doylestown Cardiology Associates - VIAA
state: Pennsylvania
city: Erie
country: United States
facility: University of Pittsburgh Medical Center UPMC Hamot
state: Pennsylvania
city: Newtown
country: United States
facility: Saint Mary Medical Center (Langhorne PA)
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center UPMC Presbyterian
state: Pennsylvania
city: East Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Germantown
country: United States
facility: The Stern Cardiovascular Foundation
state: Tennessee
city: Jackson
country: United States
facility: Jackson Clinic
state: Tennessee
city: Kingsport
country: United States
facility: Wellmont CVA Heart Institute
state: Tennessee
city: Nashville
country: United States
facility: Centennial Heart Cardiovascular Consultants LLC
state: Tennessee
city: Nashville
country: United States
facility: Saint Thomas Research Institute
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Heart Group
state: Texas
city: Corpus Christi
country: United States
facility: Cardiology Associates of Corpus Christi
state: Texas
city: Dallas
country: United States
facility: Baylor Heart & Vascular Hospital
state: Texas
city: Dallas
country: United States
facility: North Texas Heart Center
state: Texas
city: Fort Worth
country: United States
facility: Plaza Medical Center of Fort Worth
state: Texas
city: Longview
country: United States
facility: Longview Regional Medical Center
state: Texas
city: Plano
country: United States
facility: Baylor Research Institute
state: Texas
city: Temple
country: United States
facility: Scott & White Health Science Ctr
state: Texas
city: The Woodlands
country: United States
facility: EP Heart LLC
state: Texas
city: Burlington
country: United States
facility: The University of Vermont Medical Center Inc
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System
state: Virginia
city: Huntington
country: United States
facility: Saint Mary's Medical Center
state: West Virginia
city: Green Bay
country: United States
facility: Aurora BayCare Medical Center
state: Wisconsin
city: Green Bay
country: United States
facility: Bellin Memorial Hospital, Inc.
state: Wisconsin
city: Krems
country: Austria
facility: Universitätsklinikum Krems
city: Brussel
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Genk
country: Belgium
facility: Ziekenhuis Oost Limburg - Campus St.-Jan
city: Liège
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Vancouver
country: Canada
facility: Saint Paul's Hospital (Vancouver BC)
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton General Hospital / Hamilton Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)
city: Santiago
country: Chile
facility: Hospital San Juan de Dios
city: Hong Kong
country: China
facility: Grantham Hospital
city: Hong Kong
country: China
facility: Princess Margaret Hospital
city: København
country: Denmark
facility: Rigshospitalet
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Turku
country: Finland
facility: Turun Yliopistollinen keskussairaala
city: Lille
country: France
facility: Centre Hospitalier Régional Universitaire de Lille
city: Marseille
country: France
facility: Hôpital de la Timone - Centre Hospitalier Universitaire de Marseille
city: Nantes
country: France
facility: Nouvelles Cliniques Nantaises
city: Rouen Cedex 1
country: France
facility: CHU Hôpiteaux de Rouen - Hôpital Charles Nicolle
city: Saint Priest en Jarez
country: France
facility: Centre Hospitalier Universitaire Saint Étienne - Hôpital Nord
city: Bad Krozingen
country: Germany
facility: Universitäts-Herz-Zentrum Freiburg - Bad Krozingen
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion
city: Ioannina
country: Greece
facility: University Hospital of Ioannina
city: Kallithea
country: Greece
facility: Onassis Cardiac Surgery Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Hospital
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Bologna
country: Italy
facility: Policlinico Sant' Orsola - Malpighi
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Como
country: Italy
facility: Presidio Ospedaliero Sant'Anna
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello
city: Alor Setar
country: Malaysia
facility: Hospital Sultanah Bahiyah
state: Kedah
city: Kuala Lumpur
country: Malaysia
facility: Institut Jantung Negara - National Heart Institute
city: Kuala Lumpur
country: Malaysia
facility: Universiti Malaya Medical Centre
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Bergen
country: Norway
facility: Helse Bergen HF - Haukeland Universitetssjukehus
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
city: Poznań
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria-Centro Hospitalar Lisboa Norte, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Center
city: Singapore
country: Singapore
facility: Changi General Hospital
city: Singapore
country: Singapore
facility: National Heart Centre Singapore
city: Banska Bystrica
country: Slovakia
facility: Stredoslovensky ustav srdcovych a cievnych chorob a.s
city: Bratislava 37
country: Slovakia
facility: Narodny ustav srdcovych a cievnych chorob, a.s. (NUSCH)
city: Kosice
country: Slovakia
facility: Vychodoslovensky ustav srdcovych a cievnych chorob, a.s.
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital Universitari Bellvitge
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Goteborg
country: Sweden
facility: Alingsås Lasarett
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset
city: Varberg
country: Sweden
facility: Sjukhuset i Varberg
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Lugano
country: Switzerland
facility: Cardiocentro Ticino
city: St. Gallen
country: Switzerland
facility: Kantonsspital St.Gallen
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust - Harefield Hospital
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS - Manchester Royal Infirmary
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital
Study officials:
affiliation: The Cleveland Clinic
name: Bruce Wilkoff, MD
role: STUDY_CHAIR
affiliation: The Cleveland Clinic
name: Khaldoun Tarakji, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Poole JE, Swerdlow CD, Tarakji KG, Mittal S, Ellenbogen KA, Greenspon AJ, Kennergren C, Philbert BT, Moore J, Jones RC, Schaller RD, Hansalia R, Simmers T, Mihalcz A, DeBus B, Lexcen DR, Gunderson B, Wilkoff BL. Clinical performance of implantable cardioverter-defibrillator lead monitoring diagnostics. Heart Rhythm. 2022 Mar;19(3):363-371. doi: 10.1016/j.hrthm.2021.10.032. Epub 2021 Nov 9.
citation: Sohail MR, Corey GR, Wilkoff BL, Poole JE, Mittal S, Kennergren C, Greenspon AJ, Cheng A, Lande JD, Lexcen DR, Tarakji KG. Clinical Presentation, Timing, and Microbiology of CIED Infections: An Analysis of the WRAP-IT Trial. JACC Clin Electrophysiol. 2021 Jan;7(1):50-61. doi: 10.1016/j.jacep.2020.07.021. Epub 2020 Oct 28.
citation: Wilkoff BL, Boriani G, Mittal S, Poole JE, Kennergren C, Corey GR, Krahn AD, Schloss EJ, Gallastegui JL, Pickett RA, Evonich RF, Roark SF, Sorrentino DM, Sholevar DP, Cronin EM, Berman BJ, Riggio DW, Khan HH, Silver MT, Collier J, Eldadah Z, Holbrook R, Lande JD, Lexcen DR, Seshadri S, Tarakji KG. Cost-Effectiveness of an Antibacterial Envelope for Cardiac Implantable Electronic Device Infection Prevention in the US Healthcare System From the WRAP-IT Trial. Circ Arrhythm Electrophysiol. 2020 Oct;13(10):e008503. doi: 10.1161/CIRCEP.120.008503. Epub 2020 Sep 11.
citation: Wilkoff BL, Boriani G, Mittal S, Poole JE, Kennergren C, Corey GR, Love JC, Augostini R, Faerestrand S, Wiggins SS, Healey JS, Holbrook R, Lande JD, Lexcen DR, Willey S, Tarakji KG; WRAP-IT Investigators. Impact of Cardiac Implantable Electronic Device Infection: A Clinical and Economic Analysis of the WRAP-IT Trial. Circ Arrhythm Electrophysiol. 2020 May;13(5):e008280. doi: 10.1161/CIRCEP.119.008280. Epub 2020 Apr 12.
citation: Mittal S, Wilkoff BL, Kennergren C, Poole JE, Corey R, Bracke FA, Curnis A, Addo K, Martinez-Arraras J, Issa ZF, Redpath C, Moubarak J, Khelae SK, Boersma LVA, Korantzopoulos P, Krueger J, Lande JD, Morss GM, Seshadri S, Tarakji KG. The World-wide Randomized Antibiotic Envelope Infection Prevention (WRAP-IT) trial: Long-term follow-up. Heart Rhythm. 2020 Jul;17(7):1115-1122. doi: 10.1016/j.hrthm.2020.02.011. Epub 2020 Feb 19.
citation: Tarakji KG, Mittal S, Kennergren C, Corey R, Poole JE, Schloss E, Gallastegui J, Pickett RA, Evonich R, Philippon F, McComb JM, Roark SF, Sorrentino D, Sholevar D, Cronin E, Berman B, Riggio D, Biffi M, Khan H, Silver MT, Collier J, Eldadah Z, Wright DJ, Lande JD, Lexcen DR, Cheng A, Wilkoff BL; WRAP-IT Investigators. Antibacterial Envelope to Prevent Cardiac Implantable Device Infection. N Engl J Med. 2019 May 16;380(20):1895-1905. doi: 10.1056/NEJMoa1901111. Epub 2019 Mar 17.