Prevention of Arrhythmia Device Infection Trial (PADIT)

Link to ClinicalTrials.gov

Purpose

The goal of the study is to compare whether a center-wide policy of incremental antibiotic therapy will reduce CIED infection rate compared to a policy of conventional antibiotic prophylaxis in high-risk patients undergoing arrhythmia device procedures. All antibiotics used are approved for use and readily available.

Primary Outcome Measures:

  • Hospitalization attributed to device infection

Secondary Outcome Measures:

  • 1. Proven device infection not requiring surgical intervention (medically treated device infection).
  • 2. Any treatment with antibiotics for suspected device infection.
  • 3. Antibiotic-related adverse events including culture or antigen proven C. difficile infection.
  • 4. Prolongation of hospitalization due to proven or suspected adverse events from the antibiotic therapy.
  • 5. Cost benefit analysis
  • 6. Rate of device/lead extraction 12 months post patient's procedure (regardless of the cause).

Estimated Enrollment: 10800; Current Enrollment: 8,225; Study Start Date: December 2012; Estimated Study Completion Date: March 2018; Estimated Primary Completion Date: December 2017 (Final data collection date primary outcome measure)

Detailed Description:

This is a randomized prospective cluster crossover trial to track outcomes of high infection risk patients undergoing arrhythmia device procedures. Centres will be randomized to either conventional antibiotic therapy or incremental antibiotic therapy. Patients will not be randomized. Centres will be randomized to one therapy and then cross over to the next after 6 months. At one year they will randomize again and then cross over for the final time at 18 months. During each treatment period the randomized antibiotic therapy will be used on all centre patients undergoing a device implant procedure.

Ethics approval has been obtained in the all sites for waiver of consent with notification of the study (i.e. data collection is taking place to track infection rates). A third of sites obtain consent after the procedure for collection of data (but not for care, since either arm is the standard of care).

Study Groups:

Experimental Arm 1: Conventional. Preoperative Antibiotics: Cefazolin preoperative, vancomycin in penicillin allergic patients.
Experimental Arm 2: Incremental. Preoperative antibiotics (Cefazolin and vancomycin), Bacitracin pocket wash and 2 days of oral Cefalexin post operative.

Eligibility:

Ages Eligible for Study: 18 Years and older; Gender Eligible for Study: Both; Accepts Healthy Volunteers: Yes

Criteria:
Inclusion Criteria:

  1. Age 18 years or older
  2. Received one of the following procedures:
    a) A second or subsequent procedure on the arrhythmia device pocket: ICD, pacemaker, CRT-P, CRT-D generator and/or lead replacement 
    b) Pocket or lead revision
    c) System upgrade (insertion or attempted insertion of leads)
    d) New cardiac resynchronization therapy device implant (pacemaker or ICD)
  3. Patient is not known to have device infection at the time of the surgery

Locations
26 centers in Canada, 5 centers in Europe

Coordinating Center:
Population Health Research Institute: Recruiting
Hamilton, Ontario, Canada, L8L 2X2
Principal Investigator: Andrew Krahn 

Sponsors and Collaborators:
Population Health Research Institute
Canadian Institutes of Health Research (CIHR)

Investigators
Principal Investigator: Andrew Krahn, MD, University of British Columbia

Abstract

Randomized cluster crossover trials for reliable, efficient, comparative effectiveness testing: Design of the Prevention of Arrhythmia Device Infection Trial (PADIT).

Connolly SJ, Philippon F, Longtin Y, Casanova A, Birnie DH, Exner DV, Dorian P, Prakash R, Alings M, Krahn AD.

Can J Cardiol. 2013;29:652-8.

Link to abstract on PubMed

Randomized clinical trials are a major advance in clinical research methodology. However, there are myriad important questions about the effectiveness of treatments used in daily practice that are not informed by the results of randomized trials. This is in part because of important limitations inherent in the methodology of randomized efficacy trials which are performed with tight control of inclusion, exclusion, treatment, and follow-up. This approach enhances evaluation of clinical efficacy (performance in controlled situations) but increases complexity and is not well suited to test clinical effectiveness (performance under conditions of actual use). The cluster crossover trial is a new concept for efficient comparative effectiveness testing. Deep tissue infection occurs in 2% of patients after arrhythmia device implantation, usually requires system extraction, and increases mortality. There is variation in antibiotic prophylaxis used to reduce implanted device infections. To efficiently evaluate the comparative effectiveness of antibiotic strategies now in use, we designed a cluster crossover clinical trial, which randomized implanting centres to 1 of 2 prophylactic antibiotic strategies, which became the standard care at the centre for 6 months, followed by crossover to the other strategy, rerandomization, and second crossover. This method greatly reduces trial complexity because it aligns study procedures with usual clinical care and increases generalizability. Pilot studies have tested the feasibility and an 10,800-patient trial, funded by the Canadian Institutes of Health Research, is now under way. The cluster crossover randomized trial design is well suited to efficiently test comparative effectiveness of existing treatments where there is variability of practice, clinical equipoise, and minimal risk.

PMID: 23702356