Antibiotic Beads vs Negative Pressure Therapy for Open Tibia Fracture

(BeadsvsVac Trial)

Recruiting at 27 trial locations

Overseen By Heather Phipps, MPS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Maryland, Baltimore

Must not be taking: Vancomycin, Tobramycin

Disqualifiers: Chronic infection, Pregnancy, Incarceration, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

312 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatment methods for severe open tibia fractures, where the bone pierces the skin. One method uses antibiotic beads in the wound to prevent infection, while the other uses a vacuum-sealed dressing to aid healing. The goal is to determine which treatment improves leg healing over six months. Suitable participants have a severe open tibia fracture requiring multiple surgeries to clean the wound. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that antibiotic cement bead pouches help prevent infections in open fractures. This treatment places small beads filled with antibiotics directly into the wound to combat bacteria. Research has found these beads effective in controlling infections, particularly in severe bone infections like chronic osteomyelitis, a long-lasting bone infection.

Negative Pressure Wound Therapy (NPWT) has also been studied and shown to reduce infection risk and speed up healing in open fractures. This method uses a vacuum to aid wound healing by removing fluid.

Both treatments have been tested and are considered safe for managing open fractures. Patients using antibiotic beads and NPWT have generally tolerated them well, with no significant increase in side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for open tibia fractures because they offer new ways to prevent infection and promote healing. The Antibiotic Cement Bead Pouch delivers antibiotics directly to the wound site using handmade beads loaded with vancomycin and tobramycin, which can be tailored to the size of the wound. This method contrasts with standard systemic antibiotic treatments by concentrating the antibiotics right where they're needed most. On the other hand, Negative Pressure Wound Therapy (NPWT) uses a vacuum seal to remove excess fluid and shrink the wound, which helps in faster healing by maintaining an optimal wound environment. These innovative approaches could potentially improve recovery times and reduce complications compared to traditional methods.

What evidence suggests that this trial's treatments could be effective for open tibia fractures?

This trial will compare the effectiveness of two treatments for open tibia fractures. Research has shown that antibiotic cement bead pouches, one of the treatments in this trial, can greatly lower the risk of infection and reduce the need for additional surgeries due to infections. Meanwhile, negative pressure wound therapy (NPWT), the other treatment option, helps wounds heal faster by removing fluid and keeping the wound closed. Studies also indicate that NPWT can lower infection rates and reduce the need for additional surgeries. Both treatments have shown promising results in treating severe open tibia fractures. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with severe open tibia fractures needing multiple cleanings and debridement surgeries. They must plan to have internal or external fixation, receive initial surgery within 72 hours of injury, and all procedures done by a participating surgeon.

Inclusion Criteria

I am scheduled for surgery to fix a bone fracture.

Informed consent obtained

My fracture surgery will be done by a participating surgeon.

Exclusion Criteria

I cannot use antibiotic beads due to health reasons.

My surgeon thinks saving my limb is unlikely to succeed for more than 6 months.

Incarceration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either an antibiotic bead pouch or negative pressure wound therapy (NPWT) for open fracture wound management

6 weeks

Multiple visits for irrigation and debridement surgeries

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Assessments at 6 weeks, 3 months, and 6 months post-surgery

What Are the Treatments Tested in This Trial?

Interventions

• Antibiotic Cement Bead Pouch
• Negative Pressure Wound Therapy

Trial Overview The study compares two treatments for managing temporary wounds in severe open tibia fractures: an antibiotic cement bead pouch versus negative pressure wound therapy (NPWT). Participants are randomly assigned to one of the treatments and followed up at several intervals post-surgery.

How Is the Trial Designed?

Group I: Antibiotic Cement Bead Pouch Experimental Treatment 1 Intervention

The antibiotic cement bead pouch involves placing temporary non-absorbable antibiotic-laden cement beads into the open fracture wound and sealing the wound with a large occlusive dressing for prophylaxis against bacteria. The antibiotic beads used will be prepared intraoperatively by the surgical team. The bead recipe will be comprised of a ratio of 2 grams of vancomycin, 2.4 grams of tobramycin, and 40g (one bag) of PMMA cement. The beads will be handmade and approximately 10-mm in diameter. The number of beads placed in the wound will be at the discretion of the treating surgeon based on recipient wound size. As commonly practiced, the antibiotic beads may be exchanged for new beads at each subsequent irrigation and debridement surgery. The number of beads, the number of replaced beads, and the removal of the antibiotic beads will be recorded.

Group II: Negative Pressure Wound Therapy (NPWT) Active Control 1 Intervention

The NPWT system is a sealed dressing placed over the open fracture wound that includes an occlusive plastic wound dressing connected to a vacuum pump, tubing, and a canister to collect fluid. The pump creates a vacuum seal and exerts negative pressure on the wound to remove fluid and maintain a sealed environment. NPWT promotes wound healing through four primary mechanisms: 1) wound shrinkage or macrodeformation; 2) microdeformation at the foam-wound surface interface; 3) fluid removal; and 4) stabilization of the wound environment. 125 mmHg continuous negative pressure is the recommended NPWT device setting; however, the treating surgeon will be allowed to adjust these settings as clinically necessary. The frequency and timing of NPWT changes will also be at the surgeon's discretion but is expected to primarily coincide with the timing of repeat debridement, typically every 24-72 hours until definitive management has occurred.

Antibiotic Cement Bead Pouch is already approved in European Union, United States for the following indications:

Approved in European Union as Antibiotic Bead Pouch for:

• Open fractures with gross contamination
• Large zone of injury
• Devitalization of tissue
• Prevention of osteomyelitis

Approved in United States as Antibiotic Cement Bead Pouch for:

• Severe open tibia fractures requiring multiple irrigation and debridement surgeries
• Prevention of fracture-related infections

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Published Research Related to This Trial

Antibiotic bead pouches (ABPs) can deliver high concentrations of local antibiotics, potentially reducing infection rates in patients with open fractures, which is crucial for improving outcomes and lowering healthcare costs.

Vacuum-assisted closure (VAC) therapy enhances the success of surgical procedures for severe traumatic wounds, helping to minimize complications and improve healing when primary closure is not possible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wound management for severe open fractures: use of antibiotic bead pouches and vacuum-assisted closure. Prasarn, ML., Zych, G., Ostermann, PA.[2010]

Negative pressure wound therapy (NPWT) did not reduce local antibiotic concentrations in wound drainage when used with antibiotic-impregnated PMMA beads in a study involving 20 anesthetized pigs.

However, when the fascia was left open, NPWT resulted in significantly lower total elution of vancomycin and tobramycin, suggesting that fascial closure may be important for optimizing antibiotic delivery in this treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of negative pressure wound therapy on the elution of antibiotics from polymethylmethacrylate beads in a porcine simulated open femur fracture model. Large, TM., Douglas, G., Erickson, G., et al.[2016]

In a study of 60 children with acute hematogenous osteomyelitis, treatment with vancomycin-loaded calcium sulfate beads combined with negative-pressure wound therapy (NPWT) showed a similar success rate (75%) compared to conventional treatment (71.4%).

The vancomycin group experienced a significantly faster reduction in inflammatory markers (CRP levels) to 50% of initial levels in an average of 4.8 days, compared to 13 days in the conventional group, suggesting improved recovery and potentially reducing the need for prolonged antibiotic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of vancomycin-loaded calcium sulfate versus conventional surgical debridement for pediatric acute osteomyelitis: a retrospective study. Wang, B., Cheng, W., Liu, F., et al.[2023]

Negative-pressure wound therapy (NPWT) using the VAC System significantly improves healing in patients with high-grade open tibia fractures and extensive soft tissue damage, which traditionally have a high risk of complications.

By promoting wound cleaning, reducing swelling, and enhancing blood flow, NPWT can facilitate faster recovery and, in some cases, eliminate the need for more complex microsurgical procedures, allowing for limb salvage in less experienced orthopedic teams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Application of negative-pressure wound therapy in complex therapy of open tibia fractures IIIB and IIIC with massive soft tissue loss]. Babiak, I., Zakiewicz, W., Luterek, M.[2014]

In a study comparing two treatment methods for massive extremity wounds in combat injuries, the antibiotic bead pouch was found to be a safer and more cost-effective alternative to the Vacuum-Assisted Closure (VAC) Therapy system, with fewer infections and surgeries required.

The VAC Therapy system was associated with a higher rate of late infections (30%) and more unanticipated returns to the operating room, costing an additional $12,000 for 12 patients compared to the antibiotic bead pouch.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of vacuum-assisted closure to the antibiotic bead pouch for the treatment of blast injury of the extremity. Warner, M., Henderson, C., Kadrmas, W., et al.[2011]

In a study involving goats with infected wounds, wounds treated with antibiotic beads alone showed significantly lower bacterial contamination (11% of baseline) compared to those treated with both antibiotic beads and negative pressure wound therapy (67% of baseline), indicating that NPWT may reduce the effectiveness of local antibiotic treatments.

The findings suggest that surgeons should consider the potential negative impact of NPWT on local antibiotic efficacy when choosing adjunctive therapies for wound management, tailoring treatment based on the specific challenges of each case.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Negative pressure wound therapy reduces the effectiveness of traditional local antibiotic depot in a large complex musculoskeletal wound animal model. Stinner, DJ., Hsu, JR., Wenke, JC.[2012]

In a study of 21 severe compound tibia shaft fractures treated with the antibiotic bead pouch technique, only one patient developed a wound infection, indicating a high level of safety for this method in preventing infections.

At a mean follow-up of 26 months, the treatment resulted in positive outcomes, with 4 excellent, 11 good, and only 3 poor results, demonstrating the efficacy of the combined approach of antibiotic beads, external fixation, and surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of 2d and 3d degree complicated tibial shaft fractures with the PMMA bead pouch technic]. Ostermann, PA., Henry, SL., Seligson, D.[2013]

In a study of 113 patients with type IIIB open tibial shaft fractures, using an antibiotic bead pouch (ABP) for initial wound management was linked to a lower risk of fracture-related infection (FRI) requiring further surgery compared to negative pressure wound therapy (NPWT) alone or in combination with ABP.

The results suggest that initial treatment with ABP significantly reduces the odds of needing debridement or amputation due to FRI, highlighting its potential as a safer and more effective option for managing these complex fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic bead pouch versus negative pressure wound therapy at initial management of AO/OTA 42 type IIIB open tibia fracture may reduce fracture related infection: A retrospective analysis of 113 patients. Patterson, JT., Becerra, JA., Brown, M., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10561378/

The antibiotic bead pouch – a useful technique for ... The antibiotic bead pouch technique is a reasonable surgical approach for managing temporary soft tissue defects following adequate surgical debridement.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0020138322009238

Antibiotic bead pouch versus negative pressure wound ... Antibiotic bead pouch for initial coverage of type IIIB open tibial shaft fractures requiring flap coverage was associated with a lower risk of FRI requiring ...

3. trialx.com trialx.com/clinical-trials/listings/263931/antibiotic-cement-bead-pouch-versus-negative-pressure-wound-therapy/

Antibiotic Cement Bead Pouch Versus Negative Pressure ... The Beads vs Vac trial is a multi-centre randomized controlled trial of 312 participants with a severe open tibia fracture requiring multiple ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05615844/antibiotic-cement-bead-pouch-versus-negative-pressure-wound-therapy

Antibiotic Cement Bead Pouch Versus Negative Pressure ... The primary objective of this trial is to determine if the antibiotic bead pouch, compared to NPWT application, is more effective at reducing ...

5. research-studies.allinforhealth.info research-studies.allinforhealth.info/us/en/listing/12050/a-randomized-controlled-trial-7/

A Randomized Controlled Trial Comparing Antibiotic Cement ... Emerging comparative studies suggest that the antibiotic bead pouch may significantly reduce the risk of open fracture infection and its related ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12494307/

Basic science and current management for fracture ... Antibiotic bead pouches have been demonstrated to outperform negative pressure wound therapy in the management of severe open fractures.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8046830/

Outcome analysis of antibiotic-loaded poly methyl ... Antibiotics containing PMMA beads are effective in the treatment of chronic osteomyelitis and in preventing the recurrence of infection.

8. journals.lww.com journals.lww.com/jorthotrauma/fulltext/2020/08002/the_production_of_antibiotic_cement_beads.22.aspx

The Production of Antibiotic Cement Beads Antibiotic beads have demonstrated decreased rates of infection in open fractures. 1 Other indications include severe soft tissue infections and bone defects ...