World-wide Randomized Antibiotic Envelope Infection Prevention Trial

Study Overview
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Brief Summary
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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.

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

Conditions
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CIED Related Infection

Intervention / Treatment
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* Device: TYRX™ Absorbable Antibacterial Envelope


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TYRX™ envelope<br>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<br> <br> |
| No Intervention: Control<br>No TYRX™ envelope, bare CIED | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12 Month Kaplan-Meier Estimate of Major or Minor CIED Infection | 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 | Implant to 12 months | 
| 12 Month Kaplan-Meier Estimate of a CIED Procedure Related or System Related Complication | 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 | Implant to 12 months | 
| Kaplan-Meier Estimate of a Major Infection Throughout Follow-up | 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 | Throughout study follow-up Kaplan-Meier Estimate is at 36 Months |