Articulating Spacers for Knee Infections

Overseen By Melissa J Shauver, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Disqualifiers: Inability to consent, Allergies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

153 Participants Needed

Trial Summary

What is the purpose of this trial?

In the US, if an infection in an artificial knee joint doesn't heal with antibiotics alone, the standard treatment is a two-stage revision of the artificial knee. In the first stage, the surgeon will remove the artificial knee and clean out the area around the knee. They will then place an antibiotic spacer. An antibiotic spacer is a type of artificial joint that will release antibiotics into the knee space continuously over time. The spacer allows only very basic function of the knee. The patient may need to use crutches or a walker while the antibiotic spacer is in place. After surgery to place the antibiotic spacer, the surgeon may prescribe a course of antibiotics as well. Because the antibiotic spacer is not as durable as a regular artificial joint, after the infection is gone, another surgery is required to take the spacer out and put a new artificial knee joint in. There is another way for artificial joint infections to be treated. This is a one-stage revision. In this treatment, the surgeon will remove the artificial knee and clean out the area around the knee. Then the surgeon will place a new artificial knee in using a special kind of cement that contains antibiotics. The cement will release antibiotics into the knee space continuously over time (the surgeon may prescribe a course of antibiotics as well). The new artificial joint with antibiotic cement will function almost the same as the original artificial knee. This means that while the infection is healing the patient will be able to do most of the regular daily activities. However, the antibiotic cement is not as durable as what is normally used to implant an artificial knee. The artificial knee with the antibiotic cement may need to be replaced with a regular artificial knee. When replacement will need to be done is dependent on patient weight, bone strength and activity level, among other things. When it is time to replace the antibiotic cement artificial knee, the patient will have another surgery where the surgeon will take the antibiotic cement artificial knee and put a new artificial knee joint in. Investigators know that both the one- and two-stage revision work equally well to heal the infection, but investigators don't know which patients prefer or which provides better function after many years. This study will randomly assign patients to receive either a one-stage or two-stage revision and then follow them for 5 years to ask them about pain, function, and satisfaction.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Articulating Spacers for Knee Infections?

Articulating antibiotic spacers have shown an infection eradication rate of about 90% and provide better knee movement and fewer complications compared to nonarticulating spacers. They help maintain joint motion and improve patient satisfaction during the treatment of infected knee replacements. ^{1 2 3 4 5}

Is the use of articulating antibiotic spacers for knee infections safe?

Articulating antibiotic spacers are generally considered safe for treating knee infections, with studies showing high infection control rates and lower complication rates compared to nonarticulating spacers. However, there are concerns about mechanical complications and cement debris, but these are not well addressed in long-term studies. ^{1 3 5 6 7}

What makes the articulating antibiotic spacer treatment unique for knee infections?

The articulating antibiotic spacer treatment is unique because it allows for joint movement while delivering antibiotics directly to the infection site, which helps preserve knee function and improve patient satisfaction. It has a high success rate in controlling infections, especially when compared to nonarticulating spacers, and offers better range of motion and lower complication rates. ^{1 2 3 5 8}

Research Team

Adam I Edelstein, MD

Principal Investigator

Assistant Professor of Orthopaedic Surgery

Eligibility Criteria

This trial is for patients with a chronic infection in their artificial knee joint after initial replacement surgery, who are planning to have the infected joint replaced with an antibiotic spacer. They must meet specific infection criteria and be able to consent. Those with allergies to study materials, soft tissue or bone issues at the site can't participate.

Inclusion Criteria

PJI defined according to Musculoskeletal Infection Society (MSIS) 2018 Consensus Criteria

I have a long-term infection after knee replacement and need surgery to place an antibiotic device.

Exclusion Criteria

I am unable to give consent by myself.

Allergies to study materials (cement, vancomycin, tobramycin)

I have an infection at my knee replacement site.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Treatment

Surgery to remove the artificial knee and place an antibiotic spacer or new artificial knee with antibiotic cement, followed by 6 weeks of IV antibiotics

6 weeks

1 visit (in-person) for surgery, followed by regular monitoring

Postoperative Monitoring

Participants are monitored for complications and recovery progress, with questionnaires administered at 6 weeks, 6 months, 12 months, and 24 months

24 months

Multiple visits (in-person and virtual) at specified intervals

Follow-up

Participants are monitored for long-term outcomes, including pain, function, and satisfaction

5 years

Treatment Details

Interventions

• All-cement articulating spacer
• Real-component articulating spacer

Trial Overview The study compares two treatments for infected knee replacements: one-stage revision using a special cement that releases antibiotics, allowing near-normal activity but may need future replacement; versus two-stage revision which uses a temporary spacer then later surgery for durable joint placement.

Participant Groups

Group I: Observation Experimental Treatment 3 Interventions

Patients who do not wish to be randomized or who meet the randomization-specific exclusion criteria will be offered enrolment into the non-randomized, prospective observational arm of the study. The participant and their surgeon will collaboratively decide which of the 2 treatments the participant will receive.

Group II: All-cement articulating spacer Active Control 1 Intervention

An articulating spacer with a tibial and femoral component made of cement using molds, that are cemented in place; use of highdose antibiotic cement (at least 2g/batch, including vancomycin and tobramycin); use of dowels at discretion of surgeon; 6 weeks IV antibiotics; intent to reimplant definitive prosthesis if infection eradicated.

Group III: Durable, real-component articulating spacer Active Control 1 Intervention

Uses metal (or ceramicized metal) on plastic for bearing surface; use of high-dose antibiotic cement (at least 2g/batch, including vancomycin and tobramycin); no cones/sleeves, no pressurized cement in canal; use of stems/dowels/augments and level of constraint at discretion of surgeon; 6 weeks IV antibiotics; intent to leave in situ indefinitely/until clinical failure.

All-cement articulating spacer is already approved in United States, European Union for the following indications:

Approved in United States as Antibiotic spacer for:

• Periprosthetic knee infection

Approved in European Union as Articulating antibiotic spacer for:

• Chronic periprosthetic knee infection
• Infected total knee arthroplasty

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Findings from Research

Articulating cement spacers can be safely maintained for up to 7 years in patients with severe knee conditions, providing pain relief and improved function without major complications or signs of recurrent infection during that time.

However, the case highlights the risk of progressive bone loss and the potential for mechanical issues, such as fractures, necessitating careful monitoring and consideration for future surgeries like total knee arthroplasty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic-impregnated articulating cement spacer maintained for 7 years in situ for two-stage primary total knee arthroplasty: a case report. Park, YB., Ha, CW., Jang, JW., et al.[2020]

The use of self-made, antibiotic-loaded cement articulating spacers in 22 patients with infected total knee arthroplasty resulted in a 100% infection control rate after implantation, with no recurrence of infection during an average follow-up of 29.8 months.

Patients showed significant improvement in knee function, with the HSS score increasing from an average of 40.5 to 88.7 after treatment, and a high satisfaction rate of 95.3%, indicating the effectiveness and reliability of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of infected total knee arthroplasty with a self-made, antibiotic-loaded cement articulating spacer]. Zhang, Q., Zhou, YG., Chen, JY., et al.[2013]

Articulating antibiotic spacers used during two-stage exchange arthroplasty for infected total knee and hip replacements have an infection eradication rate of about 90%, making them highly effective.

These spacers also lead to better outcomes, including a higher range of motion after reimplantation and lower complication rates compared to nonarticulating spacers, indicating their safety and efficacy in appropriate patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Point/Counterpoint: Nonarticulating vs Articulating Spacers for Resection Arthroplasty of the Knee or Hip. Wyles, CC., Abdel, MP.[2021]

A new method for creating intraoperatively-made cement-on-cement antibiotic-loaded articulating spacers for infected total knee arthroplasty was developed, allowing for customization in size and antibiotic delivery without increasing surgical time.

In a study of 17 patients treated between 2004 and 2007, this method showed potential benefits in improving knee mobility and function during the recovery period, although one patient required amputation due to persistent infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperatively-made cement-on-cement antibiotic-loaded articulating spacer for infected total knee arthroplasty. Shen, H., Zhang, X., Jiang, Y., et al.[2016]

In a study of 141 patients with prosthetic knee infections, posterior-stabilized (PS) spacers showed a significantly lower rate of mechanical complications (9.3%) compared to cruciate-retaining (CR) spacers (45.5%), indicating better safety for PS spacers.

PS spacers also resulted in better functional outcomes, with higher Hospital of Special Surgery (HSS) knee scores (72.3 vs. 63.8) and greater range of motion (90.3° vs. 80.6°) compared to CR spacers, while both types effectively controlled infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cruciate-Retaining vs Posterior-Stabilized Antibiotic Cement Articulating Spacers for Two-Stage Revision of Prosthetic Knee Infection: A Retrospective Cohort Study. Lin, TL., Tsai, CH., Fong, YC., et al.[2021]

Antibiotic-loaded cement spacers are highly effective in managing periprosthetic hip and knee joint infections, achieving infection control rates over 90% with two-stage exchange arthroplasty.

The review highlights important factors such as the indications for using spacers, their production methods, and the pharmacokinetics of the antibiotics used, which are crucial for ensuring clinical success and minimizing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Use of Antibiotic-loaded Bone Cement in the Treatment of Hip and Knee Joint Infections. Anagnostakos, K.[2022]

A two-stage total knee arthroplasty (TKA) using a colistin-loaded antibiotic-impregnated cement spacer effectively managed a vancomycin-resistant Pseudomonas aeruginosa infection in a 71-year-old patient, demonstrating its efficacy in treating complex joint infections.

The local delivery of colistin via the cement spacer minimized systemic side effects, allowing for effective infection control without causing acute kidney injury, which is a common risk with systemic colistin administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-stage approach to total knee arthroplasty using colistin-loaded articulating cement spacer for vancomycin-resistant Pseudomonas aeruginosa infection in an arthritic knee. Chang, MJ., Song, MK., Shin, JH., et al.[2020]

In a study of two-stage revision total knee arthroplasty using antibiotic-impregnated articulating spacers, over 95% of cases achieved successful infection control while maintaining good functional outcomes.

However, the presence of methicillin-resistant organisms was associated with higher failure rates, indicating a need for careful management of infections caused by these resistant bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Articulating antibiotic impregnated spacers in two-stage revision of infected total knee arthroplasty. Munro, JT., Garbuz, DS., Masri, BA., et al.[2012]

References

1. England pubmed.ncbi.nlm.nih.gov

Antibiotic-impregnated articulating cement spacer maintained for 7 years in situ for two-stage primary total knee arthroplasty: a case report. [2020]

2. China pubmed.ncbi.nlm.nih.gov

[Treatment of infected total knee arthroplasty with a self-made, antibiotic-loaded cement articulating spacer]. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Point/Counterpoint: Nonarticulating vs Articulating Spacers for Resection Arthroplasty of the Knee or Hip. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Intraoperatively-made cement-on-cement antibiotic-loaded articulating spacer for infected total knee arthroplasty. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Cruciate-Retaining vs Posterior-Stabilized Antibiotic Cement Articulating Spacers for Two-Stage Revision of Prosthetic Knee Infection: A Retrospective Cohort Study. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Therapeutic Use of Antibiotic-loaded Bone Cement in the Treatment of Hip and Knee Joint Infections. [2022]

7. France pubmed.ncbi.nlm.nih.gov

Two-stage approach to total knee arthroplasty using colistin-loaded articulating cement spacer for vancomycin-resistant Pseudomonas aeruginosa infection in an arthritic knee. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Articulating antibiotic impregnated spacers in two-stage revision of infected total knee arthroplasty. [2012]