Antibiotic Eluting Graft for Joint Infections

(MAGIC Trial)

Recruiting at 12 trial locations

Overseen By Eva Serio, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Elute, Inc.

Must not be taking: Aminoglycosides

Disqualifiers: Severe renal impairment, Uncontrolled diabetes, HIV, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

204 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with infections around knee or hip implants, known as periprosthetic joint infections (PJIs). The study compares an experimental treatment using special granules with the antibiotic Tobramycin against the usual treatment method. Participants may qualify if they have a known infection in a replaced knee or hip and can attend follow-up visits. The goal is to determine if these granules can more effectively clear infections than standard methods. As an unphased trial, this study allows participants to contribute to innovative research that could enhance future treatment options.

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 prior data suggests that the EP Granules with Tobramycin device is safe for treating periprosthetic joint infections?

EP Granules with Tobramycin delivers antibiotics directly to the infection site. This targeted method can be more effective than traditional treatments. Past studies have used EP Granules with Tobramycin to treat bone infections, showing promising results.

The treatment promotes bone growth even in the presence of infection. The FDA has approved its use in clinical trials for difficult-to-treat bone infections, indicating a certain level of safety. However, as research continues, more information on its safety and effectiveness is being gathered. Always consult medical professionals to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the EP Granules with Tobramycin because they offer a novel approach to tackling joint infections. Unlike the standard of care, which typically involves leaving voids empty and using a bone cement spacer, this treatment involves using granules infused with the antibiotic tobramycin, which are placed directly into the voids. This unique delivery method could enhance the direct targeting of infections, potentially leading to more effective and faster eradication of bacteria compared to traditional methods. This innovative approach has the potential to improve patient outcomes by reducing infection rates and shortening recovery times.

What evidence suggests that this trial's treatments could be effective for periprosthetic joint infections?

Research has shown that EP Granules with Tobramycin can effectively treat infections at the source. In this trial, participants in the treatment arm will receive these granules during the first stage of a two-part surgery for infected joints. The granules deliver antibiotics directly to the infected area, potentially offering more effectiveness than traditional treatments. Patients who used these granules demonstrated promising results. This treatment not only fights infection but also promotes new bone growth, even in infected areas. This dual action could make it a strong option for treating difficult joint infections. ^{1 2 3 4 6}

Who Is on the Research Team?

Bruce Evans, MD

Principal Investigator

Holy Cross Jordan Valley Hospital

Are You a Good Fit for This Trial?

Adults at least 22 years old with infected artificial joints (PJI) and bone voids visible on X-rays can join. They must be able to follow the study plan, live in a stable location, and have a life expectancy of over a year. People with severe kidney issues, allergies to certain antibiotics or materials used in the graft, uncontrolled diabetes, metabolic disorders affecting bone growth, neuromuscular conditions, untreated cancer or those undergoing cancer treatment are excluded.

Inclusion Criteria

Life expectancy of at least 1 year

Candidates with known infected TKA, according to MSIS standard, with elevated erythrocyte sedimentation rate and C-reactive protein followed by selective aspiration of the joint if clinical suspicion is high

Radiographs demonstrating bone voids on the preoperative X-ray in patients with known Prosthetic Joint Infection (PJI)

Exclusion Criteria

Adult patients requiring a legal guardian to sign informed consent form

I have had a bone infection in the affected limb before.

I have a condition like Paget's disease that affects bone formation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 Surgery and Initial Treatment

Stage 1 surgery involves placing the device in voids for the treatment arm or leaving voids empty with a bone cement spacer for the control arm, followed by IV therapy for about six weeks.

6 weeks

Assessment and Stage 2 Surgery

Assessment of infection through pathology or needle aspiration, followed by Stage 2 surgery where revision implants are affixed.

3 weeks

Follow-up

Participants are monitored for new bone growth and absence of infection, with assessments at 12 and 24 months post Stage 1 surgery.

24 months

What Are the Treatments Tested in This Trial?

Interventions

• EP Granules with Tobramycin

Trial Overview The trial is testing EP Granules with Tobramycin as part of a two-stage surgery for joint infections against standard surgical care. Participants are randomly assigned to either receive this new treatment or undergo regular care without knowing which group they're in.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

The device will be placed in voids at Stage 1. This will be followed by IV therapy for about six weeks, followed by assessment of infection, with a stage 2 surgery to follow. (For 1.5-stage, stage 2 procedure is optional). During the stage 2 surgery, the surgeon completes the procedure with affixing the revision implants.

Group II: Control Arm Active Control 1 Intervention

In the standard of care arm, voids are left empty and a bone cement spacer placed during stage 1 surgery. This is followed by IV therapy for a minimum of six weeks, followed by a pathology assessment of infection by needle aspiration, after week 8, with a stage 2 surgery scheduled after week 9. During the stage 2 surgery, the spacer is removed and procedure completed by affixing the revision implants. For 1.5-stage procedures, the stage 2 procedure is optional.

EP Granules with Tobramycin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Tobramycin for:

• Bacterial infections
• Cystic fibrosis
• Bone and joint infections

Approved in United States as Tobramycin for:

• Bacterial infections
• Cystic fibrosis
• Bone and joint infections

Approved in Canada as Tobramycin for:

• Bacterial infections
• Bone and joint infections

Who Is Running the Clinical Trial?

Elute, Inc.

Lead Sponsor

Trials

1

Recruited

200+

Published Research Related to This Trial

In a study comparing tobramycin-impregnated cancellous bone grafts to standard cancellous bone grafts, the presence of local tobramycin did not negatively impact the healing process of the grafts.

Various methods, including imaging and biomechanical testing, confirmed that the incorporation and healing characteristics of the bone grafts remained normal despite the antibiotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of antibiotic-impregnated autogeneic cancellous bone graft on bone healing. Lindsey, RW., Probe, R., Miclau, T., et al.[2013]

Rifampicin was released the slowest from albumin- and gelatin-sealed vascular grafts, maintaining antibiotic activity for up to 48 hours, indicating its potential for prolonged effectiveness in preventing infections.

Glycopeptides showed rapid elution from sealants, losing activity within 24 hours, while pefloxacin, pristinamycin, and fusidic acid were quickly released from collagen or gelatin but retained better binding to albumin, suggesting that the choice of sealant significantly affects antibiotic retention and release rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elution of six antibiotics bonded to polyethylene vascular grafts sealed with three proteins. Galdbart, JO., Branger, C., Andreassian, B., et al.[2004]

In a study involving ten patients undergoing total hip replacement, systemic absorption of neomycin sulfate was observed when used as a wound irrigating solution.

The use of neomycin in this way poses potential risks of ototoxicity (hearing damage) and nephrotoxicity (kidney damage), highlighting the need for caution in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic absorption of neomycin irrigating solution. Weinstein, AJ., McHenry, MC., Gavan, TL.[2018]

In a study involving 15 patients undergoing total hip replacement, adding 1.2 g of tobramycin to powdered polymethylmethacrylate resulted in effective antibacterial concentrations in wound drainage fluid without raising serum levels significantly.

The use of tobramycin-impregnated bone cement showed no signs of toxicity or adverse reactions, suggesting it is a safe option for preventing infections in hip replacement surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tobramycin-impregnated cement in total hip replacements. Pritchett, JW., Bortel, DT.[2013]

Tobramycin-impregnated PMMA discs showed a reduction in bacterial adhesion by 1 log compared to control discs, indicating some level of efficacy in inhibiting bacterial colonization.

However, the results suggest that tobramycin-impregnated PMMA may not be significantly effective in preventing colonization, raising concerns about its suitability as a drug delivery vehicle for treating infections in biomaterials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The inhibition of bacterial adhesion to a tobramycin-impregnated polymethylmethacrylate substratum. Oga, M., Arizono, T., Sugioka, Y., et al.[2013]

Using a degradable polycaprolactone (PCL) polymer coating on bone grafts allows for controlled and sustained local delivery of the antibiotic tobramycin, which can improve treatment efficacy for orthopedic infections.

This method addresses the limitations of traditional antibiotic therapies by reducing burst release and maintaining effective drug levels over time, potentially decreasing the risk of persistent bacteria and antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assay method for polymer-controlled antibiotic release from allograft bone to target orthopaedic infections - biomed 2010. Sevy, JO., Slawson, MH., Grainger, DW., et al.[2010]

In vitro studies showed that vascular grafts soaked with vancomycin or tobramycin can effectively release these antibiotics for up to 3 days, with significant initial elution depending on the antibiotic concentration used.

Both antibiotics demonstrated the ability to inhibit Staphylococcus aureus growth for up to 24 hours, suggesting that local application of these antibiotics on grafts could be a promising strategy to prevent infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elution of vancomycin and tobramycin bonded to vascular grafts. Leblebicioglu, H., Sencan, I., Gunaydin, M., et al.[2013]

Local delivery of antibiotics using Vitamin D3 granules impregnated with Tobramycin or a combination of Tobramycin and Vancomycin has proven to be a simple, effective, and low-cost method for treating difficult bone and soft tissue infections, with all patients in the study responding successfully.

Vitamin D3 not only serves as a carrier for the antibiotics but also enhances immunity, promotes tissue healing, and produces an antibiotic-like substance called Cathelicidin, which helps kill bacteria and supports bone growth and mineral density.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Innovative Technique in Local Antibiotic Delivery Method in Open Infected Wounds of the Musculoskeletal System. Shekhar, C.[2020]

In a canine model of established vascular graft infections, a combination therapy of rifampin and clindamycin was found to be highly effective, resulting in all grafts being sterile after 28 days of treatment, compared to untreated controls where infections persisted.

Cefazolin treatment showed some effectiveness, with five out of seven grafts free of infection, but it was not as effective as the combination therapy, highlighting the importance of using antibiotics that concentrate in leukocytes for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of established prosthetic vascular graft infection with antibiotics preferentially concentrated in leukocytes. Wakefield, TW., Schaberg, DR., Pierson, CL., et al.[2013]

Generic tobramycin elutes more than two times faster from antibiotic-loaded polymethylmethacrylate (AL-PMMA) compared to proprietary tobramycin, based on elution studies with 1.2 g doses of each type.

The faster elution of generic tobramycin is attributed to its larger volume, which increases the amount available for release, potentially leading to higher local concentrations in tissues, although this may compromise the mechanical integrity of the PMMA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generic tobramycin elutes from bone cement faster than proprietary tobramycin. McLaren, RL., McLaren, AC., Vernon, BL.[2021]

In a study of 44 patients with resistant periprosthetic joint infections (PJIs), the use of Daptomycin/Tobramycin-impregnated PMMA beads resulted in a high clinical cure rate of 92% for infections caused by methicillin-resistant staphylococci.

The combination of tobramycin with daptomycin significantly enhanced the local antibiotic concentration in the joint, with increases of up to 3374% for onsite fabricated beads, demonstrating their potential effectiveness in treating difficult infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daptomycin-Tobramycin Cement Beads have Lethal Local Antibacterial Effect in Resistant Periprosthetic Joint Infections. Jagadale, V., Achilike, R., Nord, KM.[2020]

Tobramycin-impregnated PMMA bone cement beads provide a reliable local delivery system for antibiotics, showing effective release over 21 days, especially within the first 48 hours.

The beads maintain adequate compressive strength to prevent fragmentation during clinical use and demonstrate sustained antibacterial activity against a range of bacteria, except for Enterococcus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro characteristics of tobramycin-PMMA beads: compressive strength and leaching. Kirkpatrick, DK., Trachtenberg, LS., Mangino, PD., et al.[2022]

Citations

1. withpower.com withpower.com/trial/antibiotic-eluting-graft-for-joint-infections-ad24e

Antibiotic Eluting Graft for Joint Infections (MAGIC Trial) EP Granules with Tobramycin is unique because it delivers antibiotics directly to the infection site, which can be more effective than traditional methods that ...

2. elutinc.com elutinc.com/clinical-study/

Clinical Study Efficacy and Safety of EP Granules with Tobramycin in the 2-stage treatment of peri-prosthetic joint infections. This is a pivotal, prospective, multicenter ...

3. ctv.veeva.com ctv.veeva.com/study/multicenter-trial-of-antibiotic-eluting-graft-for-promoting-new-bone-growth-in-near-infected-bone-ca

Multicenter Trial of Antibiotic Eluting Graft for Promoting New ... The study has two arms: a treatment arm (where subjects will be treated with the EP Granules with Tobramycin investigational device in the 1st ...

4. athenaeumpub.com athenaeumpub.com/a-novel-bone-void-filler-for-use-in-prosthetic-joint-infections/

Novel Bone Void Filler for Use in Prosthetic A novel BVF, EP Granules with Tobramycin, was designed to fulfill the need for successful bone growth when infection is present.

5. elutinc.com elutinc.com/elute-inc-announces-first-clinical-trial-authorization-by-fda-for-use-of-its-antibiotic-eluting-bone-void-filler-product/

Elute, Inc. Announces First Clinical Trial Authorization by ... This is the first FDA authorization to use EP Granules with Tobramycin in patients with such difficult to treat bone infections. “We are pleased ...

6. trial.medpath.com trial.medpath.com/clinical-trial/11e9c836e74affe4/nct05361941-multicenter-trial-antibiotic-eluting-graft

Multicenter Trial of Antibiotic Eluting Graft for Promoting New ... The study has two arms: a treatment arm (where subjects will be treated with the EP Granules with Tobramycin investigational device in the 1st stage of the ...