Can Intraosseous Antibiotics Improve the Results of Irrigation & Debridement and Prosthetic Retention for PJI?

April 1, 2024 updated by: OrthoCarolina Research Institute, Inc.

Purpose of Study: In order to improve upon the variable results seen in irrigation and debridement for periprosthetic infection, we ask if the use of intraosseous regional administration of antibiotics at the time of irrigation and debridement will improve the modest success of standard irrigation and debridement. We will use the existing literature on standard irrigation and debridement procedures to compare with the results of the irrigation and debridement with the use of intraosseous antibiotics.

Impact Question:

How will this study benefit the patient? Currently when an I&D fails, the patient needs to undergo two more major procedures: 1) implant removal and 2) reimplantation of the prosthesis. Any improvement in the results of a standard irrigation and debridement procedure may decrease the number of patients having to go through further extensive procedures to cure their infection.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Type of Study:

This is a multicenter, single arm, retrospective/prospective clinical trial.

Treatment Group:

• The treatment group includes any patient with an acute perioperative infection, an acute hematogenous, or a chronic infection with unresectable components and treated with intraoperative intraosseous vancomycin during a one-stage debridement protocol. Additionally, patients will be treated with at least 4 weeks of IV antibiotics under guidance of an infectious disease specialist, and indefinite antibiotic chronic suppression.

Surgical and Antibiotic Administration Technique:

Initially, all patients will receive standard weight based cefazolin (1 gram for patients < 80kg, 2 grams for patients between 80-120kg, and 3 grams for patients over 120kg) preoperatively. Our protocol for MRSA positive patients is to use cefazolin and vancomycin preoperatively. Because irrigation and debridement in patients with gram positive infections are frequently done urgently before exact organism identification and sensitivities are available it is important to cover the patient broadly with cefazolin and vancomycin initially.

The treatment group will receive post debridement intraosseous vancomycin as described below. In total knee infections a pneumatic tourniquet must be used for the procedure. After entering the knee joint the following process is followed:

  1. Fluid is collected in four syringes and placed into two sets of aerobic and anaerobic adult blood culture bottles,
  2. Two synovial tissue cultures from different areas of the joint are obtained and sent for culture,
  3. If not enough fluid is obtained send an additional tissue culture,
  4. Remaining tissue is sent for final pathologic analysis at the end of the case.

After obtaining cultures radical synovial debridement is performed debriding the inner surface of the entire knee capsule including the posterior capsule of the knee. Modular parts will be removed, that is the polyethylene insert for knees.

Debridement and Irrigation Protocol:

After a complete synovectomy is performed along with extraction of modular parts any exposed metallic parts will be scrubbed with a sterile brush soaked in dilute betadine. A 5-step irrigation protocol will then be used for all surgeries:

  1. Pulse lavage with 3 liters of normal saline (NS),
  2. Lavage with 100 cc's of 3% H202 and 100 cc's of sterile water, a 50/50 solution left in wound for 2 minutes,
  3. Lavage 3 liters NS,
  4. Lavage with 1 liter of dilute, sterile Betadine (22.5 ml Betadine/liter NS) - left in wound for 3 minutes
  5. Pulse lavage with 3 liters of NS

After debridement and irrigation the interventional group will receive intraosseous vancomycin 500mg in 150ml of normal saline. This dose was selected based on the studies of Young (10) and Clarke (11) who used this dose in two high risk groups (revision TKA and high BMI patients) with no significant side effects or red man syndromes. This solution will be prepared by the hospital pharmacy and administered via an EZ-IO intraosseous cannula. In total knees the cannula will be placed in the proximal medial tibia using a starter drill slightly smaller than the diameter of the cannula to ensure a press fit just distal to the tibia implant in the vicinity of the pes anserine tendons. 75ccs of the vancomycin solution will be injected as a bolus. Subsequent to this the remaining 75ccs will be placed in the distal femur just proximal to the femoral component evenly split between the medial and lateral femoral condyles.

After irrigation and debridement the wound will be closed over a betadine soaked lap sponge placed between the components. Contaminated drapes and instruments will be removed and the patient will be re-prepped with new drapes. New instruments will be used to insert the new modular parts. After opening the wound and prior to inserting new modular parts the wound will be irrigated this time with the following regime:

  1. Pulse lavage with 3 liters of normal saline (NS),
  2. Lavage with 100 cc's of 3% H202 and 100 cc's of sterile water, a 50/50 solution left in wound for 2 minutes,
  3. Lavage 1 liters NS,
  4. Lavage with 1 liter of dilute, sterile Betadine (22.5 ml Betadine/liter NS) - left in wound for 3 minutes
  5. Pulse lavage with 3 liters of NS

After the modular parts are reinserted the wound is closed with monofilament sutures over drains.

Post-operative treatment will be managed by an infectious disease specialist with at least four weeks of intravenous antibiotics followed by indefinite chronic suppression as recommended by the Musculoskeletal Infection Society (Table 1). Baseline creatinine will be obtained preoperatively and on postop days 1 and 2. Infectious disease consultants will monitor peak and trough levels based on the specific antibiotic administered and they will adjust dosage as indicated.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Florida
      • Gainesville, Florida, United States, 32607
        • University of Florida
      • Weston, Florida, United States, 33331
        • Cleveland Clinic Florida
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University
    • Nebraska
      • Omaha, Nebraska, United States, 68105
        • University of Nebraska
    • New York
      • New York, New York, United States, 10279
        • New York University - Langone
    • North Carolina
      • Charlotte, North Carolina, United States, 28207
        • Atrium Mercy Hospital
      • Charlotte, North Carolina, United States, 28207
        • OrthoCarolina Research Institute/OrthoCarolina
      • Charlotte, North Carolina, United States, 28209
        • Novant Health Charlotte Orthopedic Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria (to be completed at time of consent) I. Acute perioperative periprosthetic infection in the first 90 days following primary surgery OR, II. Acute hematogenous infection with symptoms less than four weeks OR, III. Any patient with a chronic periprosthetic knee infection, or a prosthetic knee that is considered unresectable due to the presence of extremely difficult to extract implants such as cones/sleeves/or long cemented or cementless stems and indicated for an irrigation debridement procedure.

IV. Patients indicated for an irrigation debridement procedure of a knee periprosthetic knee joint infection as defined by the inclusion criteria noted above with a gram positive organism susceptible to vancomycin, defined as:

  1. A sinus communicating with the prosthesis, OR
  2. Two positive cultures obtained from the prosthesis, OR
  3. 3 of 5 criteria:

i. Elevated ESR (>30mm/hr) and CRP (>10mg/L) ii. Elevated synovial leukocyte count (>3000 cells/µL) or change of ++ on leukocyte esterase strip iii. Elevated synovial neutrophil percentage (>80%) iv. One positive culture v. Positive histological analysis of periprosthetic tissue (>5 neutrophils per high power field in 5 high power fields x400) We understand that on occasion, irrigation & debridement is performed emergently, therefore enrollment may continue without all laboratory/cultures completed. All inclusion criteria in this situation will be confirmed postoperatively.

V. Any patient >18 years old

Exclusion Criteria I. Surgical wound that cannot be closed. II. Patients with an acute PJI greater than 90 days following primary surgery (using standard implants).

III. Hematogenous infection with symptoms greater than four weeks IV. Know hypersensitivity to Vancomycin V. Major Renal disease defined as creatinine > 2.0 (See previous comments, No Red Man syndrome in 2 subsequent studies on intraosseous vancomycin in revision TKA and High BMI patients respectively (9). Additionally, systemic levels were 8 times lower with intraosseous antibiotics than IV Vancomycin.) VI. Unable to use a tourniquet due to vascular disease VII. Pregnant women VIII. Allergy to antibiotic

Screen Failure (following initial procedure):

IX. Culture negative infections whereby the infecting organism was not identified OR X. Vancomycin-resistant organisms

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Treatment Group
The treatment group includes any patient with an acute perioperative periprosthetic infection, acute hematogenous infection, or unresectable infection with a gram positive organism sensitive to vancomycin and treated with intraoperative intraosseous vancomycin. Additionally, patients will be treated with at least 4 weeks of IV antibiotics under guidance of an infectious disease specialist, and indefinite antibiotic chronic suppression.
Drug: Intraoperative Intraosseous Vancomycin
After debridement and irrigation the interventional group will receive intraosseous vancomycin 500mg in 150ml of normal saline. This solution will be prepared by the hospital pharmacy and administered via an EZ-IO intraosseous cannula. 75ccs of the vancomycin solution will be injected as a bolus. Subsequent to this the remaining 75ccs will be placed in the distal femur just proximal to the femoral component evenly split between the medial and lateral femoral condyles in knees.
Other Names:
  • Vancomycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence of Infection
Time Frame: 1 year
The primary outcome measured will be the recurrence of infection by the same organism or reinfection with a new organism as determined by the criteria using the International Consensus Meeting on PJI (1 year follow-up).
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

OrthoCarolina Research Institute, Inc.

Collaborators

American Association of Hip and Knee Surgeons

Investigators

  • Principal Investigator: Thomas Fehring, MD, OrthoCarolina Research Institute, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 14, 2020

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

October 18, 2018

First Submitted That Met QC Criteria

October 18, 2018

First Posted (Actual)

October 19, 2018

Study Record Updates

Last Update Posted (Actual)

April 2, 2024

Last Update Submitted That Met QC Criteria

April 1, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9140 (Fred Hutch/University of Washington Cancer Consortium)

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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