Treatment of Acute Periprosthetic Joint Infection Comparing Single and Planned Double-Debridement Antibiotics and Implant Retention Followed by Chronic Antibiotic Suppression

Single vs Planned Double-Debridement Antibiotics and Implant Retention Followed by Chronic Antibiotic Suppression for the Treatment of Acute Periprosthetic Joint Infection: A Prospective, Multicenter, Randomized Clinical Trial

The purpose of this research is to evaluate two different standard of care surgeries in treating periprosthetic joint infection (PJI) after total hip and knee arthroplasty. Researchers are looking at differences in outcomes following single versus planned double debridement, antibiotics, and implant retention (DAIR) for acutely infected total hip arthroplasty (THA), and total knee arthroplasties (TKAs).

Study Overview

• Status: Enrolling by invitation
• Conditions: Periprosthetic Joint Infection
• Intervention / Treatment: Procedure: Single Debridement, Antibiotics and Implant Retention; Procedure: Planned Double Debridement, Antibiotics and Implant Retention

• Study Type: Interventional
• Enrollment (Estimated): 490
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ben Mallinger, BS; Phone Number: (507) 293-7918; Email: mallinger.benjamin@mayo.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
      • Contact: Stephanie Giles; Phone Number: 904-953-9406; Email: giles.stephanie@mayo.edu
      • Principal Investigator: Cameron K Ledford, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Minnesota
      • Contact: Ben Mallinger, BS; Phone Number: 507-293-7918; Email: mallinger.benjamin@mayo.edu
      • Principal Investigator: Matthew P Abdel, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who speak English and are willing to sign the consent form

• Patients with acute early postoperative infection (symptoms ≤ 4 weeks from surgery; symptoms < 4 weeks in duration) and acute hematogenous infection (greater than 4 weeks from surgery; symptoms < 3 weeks in duration) of a primary total knee or total hip arthroplasty, defined as:

  • A sinus communicating with the prosthesis OR
  • Two positive cultures obtained from the prosthesis OR
  • 4 of 5 criteria: Elevated ESR (> 30mm/hr) and CRP (> 10mg/L); Elevated synovial leukocyte count (>3000 cells/μL) or change of ++ on; leukocyte esterase strip; Elevated synovial neutrophil percentage (> 80%); One positive culture; Positive histological analysis of periprosthetic tissue (> 5 neutrophils per high; Power field in 5 high power fields x 400).
• OR Patient with an acute infection diagnosed clinically by an orthopedic surgeon treated with DAIR

Exclusion Criteria:

• Patients with a chronic PJI, defined as: presentation of symptoms > 4 weeks in duration.
• Revision surgery or previous two-stage reimplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Single DAIR Surgery Arm; Subjects will undergo a single Debridement Antibiotics and Implant Retention (DAIR) surgical procedure, along with IV antibiotics and followed by oral suppressive antibiotics. This method is currently used and considered to be standard of care.	Procedure: Single Debridement, Antibiotics and Implant Retention; Surgical debridement and wash out of infected joint. The polyethylene (plastic) insert, which acts as the articulating surface (modular component) of the prosthesis, will be removed and the exposed surfaces scrubbed, sterilized, and soaked. A new modular component will be placed with additional irrigation and antiseptic soak. Tissue cultures will be sent to the lab for further evaluation and antibiotic guidance. After the operation subjects will continue six weeks of IV antibiotics followed by oral antibiotic suppression for the life of the implant or at least two years after operation.
Active Comparator: Double DAIR Surgery Arm; Subjects will undergo planned double Debridement Antibiotics and Implant Retention (DAIR) surgical procedure, along with IV antibiotics and followed by oral suppressive antibiotics. This method is currently used and considered to be standard of care.	Procedure: Planned Double Debridement, Antibiotics and Implant Retention; Surgical debridement and wash out of infected joint with an additional irrigation and debridement scheduled for approximately 5 days after the initial DAIR. During the first washout, antibiotic cement beads will be placed in the joint and these will remain in the interim until they are removed during the second washout. During the second DAIR, the antibiotic beads are removed, and the modular components are once again removed and replaced with new components. Exposed surfaces are again irrigated and debrided following a standardized protocol. A six-week course of IV antibiotics will follow the DAIR with additional oral antibiotics for the life of the component (standard of care) or at least a minimum of two years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects free from failure	Total number of subjects considered failure free at one year from surgical DAIR procedure. Failure is defined as reoperation for infection within one year from surgical procedure.	1 year following DAIR.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Readmission within 90 days of the surgical DAIR procedure	Total number of subjects to required hospital readmission within 90 days of DAIR.	90 days following DAIR procedure
1-year surgical reoperation rate	Total number of subjects to require reoperation or revision with or without infection within one year from the surgical DAIR procedure.	1 year following DAIR procedure
5-year surgical reoperation rate	Total number of subjects to require reoperation or revision with or without infection within five years from the surgical DAIR procedure.	5 years following DAIR procedure
10-year surgical revision rate	Total number of subjects to require reoperation or revision with or without infection within ten years from the surgical DAIR procedure.	10 years following DAIR procedure
Hospital length of stay	Total number of days subjects were admitted to the hospital	Approximately 2 weeks following DAIR procedure
Resource analysis	Hospital admission cost comparison between the two study arms	Approximately 2 weeks following DAIR procedure
Clinical Outcome Scores	Evaluation of patient reported Harris Hip or Knee Society Scores	1, 5, and 10 years following DAIR procedure
Adverse events	Total number of subjects to experience adverse events related to either drug or the surgical procedure	10 years following DAIR procedure
Survivorship	Total number of subject deaths post-surgical DAIR procedure	10 years following DAIR procedure

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Matthew Abdel, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2023
• Primary Completion (Estimated): March 1, 2032
• Study Completion (Estimated): March 1, 2032

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: November 28, 2022
• First Posted (Actual): December 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Total knee arthroplasty; Total hip arthroplasty
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Arthritis; Infections; Communicable Diseases; Arthritis, Infectious; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: 22-006739

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No