Antibiotic Beads vs Negative Pressure Therapy for Open Tibia Fracture

(BeadsvsVac Trial)

Recruiting at 19 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

Trial Summary

What is the purpose of this trial?

The Beads vs Vac trial is a multi-centre randomized controlled trial of 312 participants with a severe open tibia fracture requiring multiple irrigation and debridement surgeries. Eligible participants will be randomized to receive either an antibiotic bead pouch or negative pressure wound therapy (NPWT) for their temporary open fracture wound management. Outcomes will be assessed at 6 weeks, 3 months, and 6 months post-surgery. The primary outcome will be a composite outcome to evaluate clinical status six months after randomization. Components of the composite outcome will be hierarchically assessed in the following order: 1) all-cause mortality, 2) injury-related amputation of the lower extremity, 3) unplanned reoperation to manage wound complications, infection, or delayed fracture healing, and 4) clinical fracture healing as assessed using the Functional IndeX for Trauma (FIX-IT) instrument. The secondary outcomes will independently assess the four components of the primary outcome. This is a Phase III trial.

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 Antibiotic Beads vs Negative Pressure Therapy for Open Tibia Fracture?

Research suggests that using antibiotic bead pouches can provide high concentrations of local antibiotics, which may help reduce infection rates in severe open fractures. Additionally, negative pressure wound therapy (NPWT) has been shown to improve healing by removing infectious material and promoting tissue growth, potentially reducing complications and costs in managing severe open fractures. ^{1 2 3 4 5}

Is the use of antibiotic beads and negative pressure therapy generally safe for treating open fractures?

Both antibiotic beads and negative pressure therapy have been used safely in treating open fractures. Antibiotic beads provide high local antibiotic levels, and negative pressure therapy can help with wound healing, though it may require more resources and trained staff. Some studies noted infections, but these treatments are generally considered safe with proper medical supervision. ^{1 3 5 6 7}

How is the treatment for open tibia fractures using antibiotic beads and negative pressure therapy different from other treatments?

This treatment combines antibiotic beads, which release antibiotics directly at the fracture site, with negative pressure wound therapy (a method that uses suction to help wounds heal), potentially reducing infection risk more effectively than using either method alone. ^{3 4 5 6 8}

Eligibility Criteria

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

I had surgery to clean a wound within 3 days of getting hurt.

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.

Anticipated problems, in the judgment of research personnel, with maintaining follow-up with the patient

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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 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]

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]

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 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 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 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]

References

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

Wound management for severe open fractures: use of antibiotic bead pouches and vacuum-assisted closure. [2010]

2. Poland 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]. [2014]

3. Netherlands 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. [2023]

4. United States 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. [2012]

5. United States 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. [2016]

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

[Treatment of 2d and 3d degree complicated tibial shaft fractures with the PMMA bead pouch technic]. [2013]

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

Comparison of vacuum-assisted closure to the antibiotic bead pouch for the treatment of blast injury of the extremity. [2011]

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

Efficacy and safety of vancomycin-loaded calcium sulfate versus conventional surgical debridement for pediatric acute osteomyelitis: a retrospective study. [2023]