World-wide Randomized Antibiotic Envelope Infection Prevention Trial
WRAP-IT
Cardiac Implantable Electronic Device (CIED) Antibiotic Envelope Infection Prevention Trial
1 other identifier
interventional
7,075
25 countries
181
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Jan 2015
Longer than P75 for phase_4
181 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 22, 2014
CompletedFirst Posted
Study publicly available on registry
October 29, 2014
CompletedStudy Start
First participant enrolled
January 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2018
CompletedResults Posted
Study results publicly available
October 24, 2019
CompletedNovember 5, 2019
October 1, 2019
3.7 years
October 22, 2014
October 2, 2019
October 23, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
12 Month Kaplan-Meier Estimate of Major CIED Infection Rate
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
Implant to 12 months
Secondary Outcomes (3)
12 Month Kaplan-Meier Estimate of Major or Minor CIED Infection
Implant to 12 months
12 Month Kaplan-Meier Estimate of a CIED Procedure Related or System Related Complication
Implant to 12 months
Kaplan-Meier Estimate of a Major Infection Throughout Follow-up
Throughout study follow-up Kaplan-Meier Estimate is at 36 Months
Study Arms (2)
TYRX™ envelope
ACTIVE COMPARATORThe 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.
Control
NO INTERVENTIONNo TYRX™ envelope, bare CIED
Interventions
Eligibility Criteria
You may qualify if:
- 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
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Medtronic Cardiac Rhythm and Heart Failurelead
- The Cleveland Cliniccollaborator
Study Sites (181)
Alaska Heart Institute
Anchorage, Alaska, United States
Tri-City Cardiology Consultants
Mesa, Arizona, United States
Arizona Arrhythmia Consultants
Scottsdale, Arizona, United States
Chula Vista Cardiac Center
Chula Vista, California, United States
Cardiovascular Consultants Heart Center
Fresno, California, United States
UCSD Medical Center
La Jolla, California, United States
Eisenhower Desert Cardiology Center
Rancho Mirage, California, United States
University of California San Francisco UCSF Medical Center
San Francisco, California, United States
Stanford Hospital & Clinics
Stanford, California, United States
Saint Joseph's Medical Center
Stockton, California, United States
Penrose St. Francis Hospital
Colorado Springs, Colorado, United States
Swedish Medical Center
Englewood, Colorado, United States
SCL Physicians Heart Institute of Colorado
Lafayette, Colorado, United States
Danbury Hospital
Danbury, Connecticut, United States
Hartford Hospital
Hartford, Connecticut, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, United States
Florida Electrophysiology Associates
Atlantis, Florida, United States
Clearwater Cardiovascular & Interventional Consultants
Clearwater, Florida, United States
The Cardiac & Vascular Institute
Gainesville, Florida, United States
University of Florida Health Shands Hospital
Gainesville, Florida, United States
Kootenai Heart Clinics Northwest
Coeur d'Alene, Idaho, United States
NorthShore University Health System
Evanston, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
Prairie Education & Research Cooperative (Springfield IL)
Springfield, Illinois, United States
Saint Vincent Medical Group
Indianapolis, Indiana, United States
Iowa Heart Center
West Des Moines, Iowa, United States
The University Kansas Medical Center Research Institute Inc
Kansas City, Kansas, United States
Lexington Cardiac Research Foundation
Lexington, Kentucky, United States
Norton Cardiovascular Associates
Louisville, Kentucky, United States
Cardiovascular Research Foundation of Louisiana
Baton Rouge, Louisiana, United States
Advanced Cardiovascular Specialists
Shreveport, Louisiana, United States
Maine Medical Center
Scarborough, Maine, United States
MedStar Health Research Institute
Baltimore, Maryland, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, United States
Delmarva Heart Research Foundation Inc
Salisbury, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
Sparrow Clinical Research Institute
Lansing, Michigan, United States
DLP Marquette Physicians Practices Inc
Marquette, Michigan, United States
Upper Michigan Cardiovascular Associates PC
Marquette, Michigan, United States
Beaumont Hospital - Royal Oak
Royal Oak, Michigan, United States
Great Lakes Heart and Vascular Institute PC
Saint Joseph, Michigan, United States
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, United States
University of Minnesota Medical Center
Minneapolis, Minnesota, United States
North Memorial Heart and Vascular Institute
Robbinsdale, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
CentraCare Heart & Vascular Center
Saint Cloud, Minnesota, United States
United Heart and Vascular Clinic
Saint Paul, Minnesota, United States
Hattiesburg Clinic/ Forrest General
Hattiesburg, Mississippi, United States
Mid America Heart Institute (MAHI)
Kansas City, Missouri, United States
Mercy Hospital Springfield
Springfield, Missouri, United States
Saint Anthonys Medical Center
St Louis, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
University of Nebraska
Omaha, Nebraska, United States
Englewood Hospital & Medical Center
Englewood, New Jersey, United States
Jersey Shore University Medical Center
Neptune City, New Jersey, United States
Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States
The Valley Hospital
Ridgewood, New Jersey, United States
Lourdes Cardiology Services
Voorhees Township, New Jersey, United States
Saint Joseph's Hospital Health Center
Liverpool, New York, United States
Cornell University Medical Center
New York, New York, United States
Mount Sinai Saint Luke's Hospital
New York, New York, United States
New York Presbyterian Hospital
New York, New York, United States
NYU
New York, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
Westchester Medical Center
Valhalla, New York, United States
Asheville Cardiology Associate PA
Asheville, North Carolina, United States
Novant Health Heart and Vascular Institute
Charlotte, North Carolina, United States
Duke University Medical Center (DUMC)
Durham, North Carolina, United States
Raleigh Cardiology Associates
Raleigh, North Carolina, United States
Novant Health Forsyth Medical Center
Winston-Salem, North Carolina, United States
Wake Forest University Health Sciences / Baptist Medical Center / North Carolina Baptist Hospital
Winston-Salem, North Carolina, United States
Akron General Medical Center
Akron, Ohio, United States
Northeast Ohio Cardiovascular Specialists
Akron, Ohio, United States
The Lindner Research Center
Cincinnati, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
University Hospitals Case Medical Center
Cleveland, Ohio, United States
OhioHealth Riverside Methodist Hospital
Columbus, Ohio, United States
The Ohio State University
Columbus, Ohio, United States
Saint Elizabeth Health Center
Poland, Ohio, United States
Mount Carmel East
Westerville, Ohio, United States
Oklahoma Heart Hospital Research Foundation
Oklahoma City, Oklahoma, United States
University of Oklahoma Health Science Center (OUHSC)
Oklahoma City, Oklahoma, United States
Oklahoma Heart Institute
Tulsa, Oklahoma, United States
Legacy Medical Group
Portland, Oregon, United States
Oregon Health & Science University Hospital
Portland, Oregon, United States
Providence Health & Services
Portland, Oregon, United States
Lehigh Valley Hospital Cedar Crest
Allentown, Pennsylvania, United States
Saint Luke's Hospital
Bethlehem, Pennsylvania, United States
Geisinger Medical Center
Danville, Pennsylvania, United States
Doylestown Cardiology Associates - VIAA
Doylestown, Pennsylvania, United States
University of Pittsburgh Medical Center UPMC Hamot
Erie, Pennsylvania, United States
Saint Mary Medical Center (Langhorne PA)
Newtown, Pennsylvania, United States
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States
Pennsylvania Hospital
Philadelphia, Pennsylvania, United States
Temple University Hospital
Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States
University of Pittsburgh Medical Center UPMC Presbyterian
Pittsburgh, Pennsylvania, United States
The Miriam Hospital
East Providence, Rhode Island, United States
The Stern Cardiovascular Foundation
Germantown, Tennessee, United States
Jackson Clinic
Jackson, Tennessee, United States
Wellmont CVA Heart Institute
Kingsport, Tennessee, United States
Centennial Heart Cardiovascular Consultants LLC
Nashville, Tennessee, United States
Saint Thomas Research Institute
Nashville, Tennessee, United States
Amarillo Heart Group
Amarillo, Texas, United States
Cardiology Associates of Corpus Christi
Corpus Christi, Texas, United States
Baylor Heart & Vascular Hospital
Dallas, Texas, United States
North Texas Heart Center
Dallas, Texas, United States
Plaza Medical Center of Fort Worth
Fort Worth, Texas, United States
Longview Regional Medical Center
Longview, Texas, United States
Baylor Research Institute
Plano, Texas, United States
Scott & White Health Science Ctr
Temple, Texas, United States
EP Heart LLC
The Woodlands, Texas, United States
The University of Vermont Medical Center Inc
Burlington, Vermont, United States
Virginia Commonwealth University Health System
Richmond, Virginia, United States
Saint Mary's Medical Center
Huntington, West Virginia, United States
Aurora BayCare Medical Center
Green Bay, Wisconsin, United States
Bellin Memorial Hospital, Inc.
Green Bay, Wisconsin, United States
Universitätsklinikum Krems
Krems, Austria
Universitair Ziekenhuis Brussel
Brussels, Belgium
Ziekenhuis Oost Limburg - Campus St.-Jan
Genk, Belgium
Centre Hospitalier Regional de la Citadelle
Liège, Belgium
Saint Paul's Hospital (Vancouver BC)
Vancouver, British Columbia, Canada
Hamilton General Hospital / Hamilton Health Sciences
Hamilton, Ontario, Canada
University of Ottawa Heart Institute
Ottawa, Ontario, Canada
Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)
Québec, Canada
Hospital San Juan de Dios
Santiago, Chile
Grantham Hospital
Hong Kong, China
Princess Margaret Hospital
Hong Kong, China
Rigshospitalet
Copenhagen, Denmark
Helsinki University Hospital
Helsinki, Finland
Turun Yliopistollinen keskussairaala
Turku, Finland
Centre Hospitalier Régional Universitaire de Lille
Lille, France
Hôpital de la Timone - Centre Hospitalier Universitaire de Marseille
Marseille, France
Nouvelles Cliniques Nantaises
Nantes, France
CHU Hôpiteaux de Rouen - Hôpital Charles Nicolle
Rouen, France
Centre Hospitalier Universitaire Saint Étienne - Hôpital Nord
Saint-Priest-en-Jarez, France
Universitäts-Herz-Zentrum Freiburg - Bad Krozingen
Bad Krozingen, Germany
Universitätsmedizin Rostock
Rostock, Germany
University General Hospital of Heraklion
Heraklion, Greece
University Hospital of Ioannina
Ioannina, Greece
Onassis Cardiac Surgery Center
Kallithea, Greece
Rabin Medical Center - Beilinson Hospital
Petah Tikva, Israel
Chaim Sheba Medical Center
Ramat Gan, Israel
Policlinico Sant' Orsola - Malpighi
Bologna, Italy
Azienda Ospedaliera Spedali Civili di Brescia
Brescia, Italy
Presidio Ospedaliero Sant'Anna
Como, Italy
Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello
Pisa, Italy
Hospital Sultanah Bahiyah
Alor Star, Kedah, Malaysia
Institut Jantung Negara - National Heart Institute
Kuala Lumpur, Malaysia
Universiti Malaya Medical Centre
Kuala Lumpur, Malaysia
Catharina Ziekenhuis
Eindhoven, Netherlands
St. Antonius Ziekenhuis
Nieuwegein, Netherlands
Helse Bergen HF - Haukeland Universitetssjukehus
Bergen, Norway
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
Lublin, Poland
Szpital Kliniczny Przemienienia Panskiego
Poznan, Poland
Hospital de Santa Maria-Centro Hospitalar Lisboa Norte, EPE
Lisbon, Portugal
Centro Hospitalar do Porto
Porto, Portugal
King Faisal Specialist Hospital & Research Center
Riyadh, Saudi Arabia
Changi General Hospital
Singapore, Singapore
National Heart Centre Singapore
Singapore, Singapore
Stredoslovensky ustav srdcovych a cievnych chorob a.s
Banská Bystrica, Slovakia
Narodny ustav srdcovych a cievnych chorob, a.s. (NUSCH)
Bratislava, Slovakia
Vychodoslovensky ustav srdcovych a cievnych chorob, a.s.
Košice, Slovakia
Hospital Marqués de Valdecilla
Santander, Cantabria, Spain
Hospital Universitari Bellvitge
Barcelona, Spain
Hospital Universitario La Paz
Madrid, Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain
Alingsås Lasarett
Gothenburg, Sweden
Sahlgrenska Universitetssjukhuset
Gothenburg, Sweden
Karolinska Universitetssjukhuset
Stockholm, Sweden
Sjukhuset i Varberg
Varberg, Sweden
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland
Cardiocentro Ticino
Lugano, Switzerland
Kantonsspital St.Gallen
Sankt Gallen, Switzerland
Liverpool Heart and Chest Hospital NHS Foundation Trust
Liverpool, United Kingdom
Royal Brompton & Harefield NHS Foundation Trust - Harefield Hospital
London, United Kingdom
Central Manchester University Hospitals NHS - Manchester Royal Infirmary
Manchester, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital
Newcastle upon Tyne, United Kingdom
Related Publications (6)
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.
PMID: 34767985DERIVEDSohail 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.
PMID: 33478712DERIVEDWilkoff 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.
PMID: 32915063DERIVEDWilkoff 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.
PMID: 32281393DERIVEDMittal 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.
PMID: 32087357DERIVEDTarakji 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.
PMID: 30883056DERIVED
Results Point of Contact
- Title
- Daniel Lexcen, Sr. Clinical Program Manager
- Organization
- Medtronic
Study Officials
- STUDY CHAIR
Bruce Wilkoff, MD
The Cleveland Clinic
- PRINCIPAL INVESTIGATOR
Khaldoun Tarakji, MD
The Cleveland Clinic
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 22, 2014
First Posted
October 29, 2014
Study Start
January 1, 2015
Primary Completion
September 1, 2018
Study Completion
September 1, 2018
Last Updated
November 5, 2019
Results First Posted
October 24, 2019
Record last verified: 2019-10