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

NCT03713528 | Enrolling By Invitation Phase 4 DMC FDA Drug

• 1 other identifier: 9140
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Joint Infection

Outcome Measures

Primary Outcomes (1)

• Recurrence of Infection

  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

Study Arms (1)

Treatment Group

OTHER

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

Interventions

Intraoperative Intraosseous Vancomycin DRUG

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.

Also known as: Vancomycin

Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A sinus communicating with the prosthesis, OR
• Two positive cultures obtained from the prosthesis, OR
• of 5 criteria:
• V. Any patient \>18 years old

You may not qualify if:

• 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

Sponsors & Collaborators

• OrthoCarolina Research Institute, Inc.: lead
• American Association of Hip and Knee Surgeons: collaborator

Study Sites (10)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Florida

Gainesville, Florida, 32607, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

University of Nebraska

Omaha, Nebraska, 68105, United States

Location

New York University - Langone

New York, New York, 10279, United States

Location

Atrium Mercy Hospital

Charlotte, North Carolina, 28207, United States

Location

OrthoCarolina Research Institute/OrthoCarolina

Charlotte, North Carolina, 28207, United States

Location

Novant Health Charlotte Orthopedic Hospital

Charlotte, North Carolina, 28209, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (11)

• Hartman MB, Fehring TK, Jordan L, Norton HJ. Periprosthetic knee sepsis. The role of irrigation and debridement. Clin Orthop Relat Res. 1991 Dec;(273):113-8.

  PMID: 1959257 BACKGROUND

• Bradbury T, Fehring TK, Taunton M, Hanssen A, Azzam K, Parvizi J, Odum SM. The fate of acute methicillin-resistant Staphylococcus aureus periprosthetic knee infections treated by open debridement and retention of components. J Arthroplasty. 2009 Sep;24(6 Suppl):101-4. doi: 10.1016/j.arth.2009.04.028. Epub 2009 Jun 24.

  PMID: 19553077 BACKGROUND

• Fehring TK, Odum SM, Berend KR, Jiranek WA, Parvizi J, Bozic KJ, Della Valle CJ, Gioe TJ. Failure of irrigation and debridement for early postoperative periprosthetic infection. Clin Orthop Relat Res. 2013 Jan;471(1):250-7. doi: 10.1007/s11999-012-2373-9.

  PMID: 22552768 BACKGROUND

• Bryan AJ, Abdel MP, Sanders TL, Fitzgerald SF, Hanssen AD, Berry DJ. Irrigation and Debridement with Component Retention for Acute Infection After Hip Arthroplasty: Improved Results with Contemporary Management. J Bone Joint Surg Am. 2017 Dec 6;99(23):2011-2018. doi: 10.2106/JBJS.16.01103.

  PMID: 29206791 BACKGROUND

• Urish KL, Bullock AG, Kreger AM, Shah NB, Jeong K, Rothenberger SD; Infected Implant Consortium. A Multicenter Study of Irrigation and Debridement in Total Knee Arthroplasty Periprosthetic Joint Infection: Treatment Failure Is High. J Arthroplasty. 2018 Apr;33(4):1154-1159. doi: 10.1016/j.arth.2017.11.029. Epub 2017 Nov 21.

  PMID: 29221840 BACKGROUND

• Young SW, Zhang M, Freeman JT, Vince KG, Coleman B. Higher cefazolin concentrations with intraosseous regional prophylaxis in TKA. Clin Orthop Relat Res. 2013 Jan;471(1):244-9. doi: 10.1007/s11999-012-2469-2.

  PMID: 22773397 BACKGROUND

• Young SW, Zhang M, Freeman JT, Mutu-Grigg J, Pavlou P, Moore GA. The Mark Coventry Award: Higher tissue concentrations of vancomycin with low-dose intraosseous regional versus systemic prophylaxis in TKA: a randomized trial. Clin Orthop Relat Res. 2014 Jan;472(1):57-65. doi: 10.1007/s11999-013-3038-z.

  PMID: 23666589 BACKGROUND

• Young SW, Roberts T, Johnson S, Dalton JP, Coleman B, Wiles S. Regional Intraosseous Administration of Prophylactic Antibiotics is More Effective Than Systemic Administration in a Mouse Model of TKA. Clin Orthop Relat Res. 2015 Nov;473(11):3573-84. doi: 10.1007/s11999-015-4464-x. Epub 2015 Jul 30.

  PMID: 26224291 BACKGROUND

• Young SW, Zhang M, Moore GA, Pitto RP, Clarke HD, Spangehl MJ. The John N. Insall Award: Higher Tissue Concentrations of Vancomycin Achieved With Intraosseous Regional Prophylaxis in Revision TKA: A Randomized Controlled Trial. Clin Orthop Relat Res. 2018 Jan;476(1):66-74. doi: 10.1007/s11999.0000000000000013.

  PMID: 29529618 BACKGROUND

• Chin SJ, Moore GA, Zhang M, Clarke HD, Spangehl MJ, Young SW. The AAHKS Clinical Research Award: Intraosseous Regional Prophylaxis Provides Higher Tissue Concentrations in High BMI Patients in Total Knee Arthroplasty: A Randomized Trial. J Arthroplasty. 2018 Jul;33(7S):S13-S18. doi: 10.1016/j.arth.2018.03.013. Epub 2018 Mar 15.

  PMID: 29655497 BACKGROUND

• Lichstein P, Gehrke T, Lombardi A, Romano C, Stockley I, Babis G, Bialecki J, Bucsi L, Cai X, Cao L, de Beaubien B, Erhardt J, Goodman S, Jiranek W, Keogh P, Lewallen D, Manner P, Marczynski W, Mason JB, Mulhall K, Paprosky W, Patel P, Piccaluga F, Polkowski G, Pulido L, Stockley I, Suarez J, Thorey F, Tikhilov R, Velazquez JD, Winkler H. One-stage vs two-stage exchange. J Arthroplasty. 2014 Feb;29(2 Suppl):108-11. doi: 10.1016/j.arth.2013.09.048. Epub 2013 Oct 1. No abstract available.

  PMID: 24360339 BACKGROUND

MeSH Terms

Interventions

Vancomycin

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Thomas Fehring, MD

  OrthoCarolina Research Institute, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: multicenter, single arm, retrospective/prospective clinical trial

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: October 19, 2018
• Study Start: January 14, 2020
• Primary Completion: January 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)