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

NCT ID: NCT03713528

Last Updated: 2025-03-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ENROLLING_BY_INVITATION

Clinical Phase

PHASE4

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-14

Study Completion Date

2026-06-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Joint Infection

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

multicenter, single arm, retrospective/prospective clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type OTHER

Intraoperative Intraosseous Vancomycin

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Vancomycin

Eligibility Criteria

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Inclusion Criteria

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


V. Any patient \>18 years old

Exclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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American Association of Hip and Knee Surgeons

OTHER

Sponsor Role collaborator

OrthoCarolina Research Institute, Inc.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas Fehring, MD

Role: PRINCIPAL_INVESTIGATOR

OrthoCarolina Research Institute, Inc.

Locations

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University of California, San Francisco

San Francisco, California, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Cleveland Clinic Florida

Weston, Florida, United States

Site Status

Rush University

Chicago, Illinois, United States

Site Status

University of Nebraska

Omaha, Nebraska, United States

Site Status

New York University - Langone

New York, New York, United States

Site Status

Atrium Mercy Hospital

Charlotte, North Carolina, United States

Site Status

OrthoCarolina Research Institute/OrthoCarolina

Charlotte, North Carolina, United States

Site Status

Novant Health Charlotte Orthopedic Hospital

Charlotte, North Carolina, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 1959257 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19553077 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22552768 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29206791 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29221840 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22773397 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23666589 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26224291 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29529618 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29655497 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24360339 (View on PubMed)

Other Identifiers

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9140

Identifier Type: -

Identifier Source: org_study_id

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