Calcium Sulfate Antibiotic Depot for Open Tibia Fractures

Recruiting at 10 trial locations

Overseen By Rachel B Seymour, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Wake Forest University Health Sciences

Disqualifiers: Allergy to vancomycin, Hypercalcemia, Pregnant, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: During index hospitalization

497 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this randomized clinical trial is to study the best treatment for open lower leg fractures to prevent infection. The main questions it aims to answer is if treating tibia fracture patients with a calcium sulfate antibiotic depot is better at preventing infection that the standard of care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is the Calcium Sulfate Antibiotic Depot safe for use in humans?

Research on calcium sulfate antibiotic depots, like Stimulan, shows they are generally safe for treating bone infections, with some studies noting moderate to intense inflammatory reactions and fibrosis (thickening of tissue) in animal models. No significant changes in blood calcium levels were observed, suggesting a good safety profile. ^{1 2 3 4 5}

What makes the Intramedullary Calcium Sulfate Antibiotic Depot treatment unique for open tibia fractures?

This treatment is unique because it uses a calcium sulfate-based material to locally deliver high concentrations of antibiotics directly to the fracture site, which helps reduce infection and promote bone healing without the systemic side effects of traditional antibiotic treatments. ^{2 3 6 7 8}

What data supports the effectiveness of the treatment Intramedullary Calcium Sulfate Antibiotic Depot, STIMULAN, Calcium Sulfate Antibiotic Depot for open tibia fractures?

Research shows that antibiotic-loaded calcium sulfate is effective in treating severe open fractures by reducing infection and aiding in bone healing. It has been used successfully in combat-related injuries and chronic bone infections, demonstrating its potential to deliver high local doses of antibiotics and promote fracture healing. ^{2 3 6 7 9}

Who Is on the Research Team?

Rachel Seymour, PhD

Principal Investigator

Wake Forest University Health Sciences

Jessica Rivera, MD

Principal Investigator

Louisiana State University Health Science Center

Are You a Good Fit for This Trial?

Adults over 18 with a Type II or III open tibia fracture needing an intramedullary nail can join. Excluded are those under 18, allergic to vancomycin/tobramycin, with high blood calcium levels, without contact info, prisoners, non-English/Spanish speakers, and pregnant or breastfeeding women.

Inclusion Criteria

I have a severe open fracture in my shinbone needing surgery with a metal rod.

Exclusion Criteria

Allergy to vancomycin or tobramycin

I am under 18 years old.

Hypercalcemia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a calcium sulfate antibiotic depot or standard intramedullary nailing during definitive fixation of open tibia fractures

During index hospitalization

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with data capture at multiple time points

12 months

5 visits (in-person) at baseline, 6 weeks, 3 months, 6 months, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Intramedullary Calcium Sulfate Antibiotic Depot

Trial Overview The trial is testing if using calcium sulfate mixed with antibiotics (vancomycin hydrochloride or gentamicin) inside the bone is better at preventing infections compared to the usual treatment in patients with severe lower leg fractures.

How Is the Trial Designed?

Group I: Standard of care intramedullary nail (SN) Experimental Treatment 1 Intervention

Standard of care intramedullary nail

Group II: Intramedullary calcium sulfate antibiotic depot prior to Intramedullary nailing (IMN) placement (CS) Experimental Treatment 2 Interventions

The intramedullary calcium sulfate antibiotic depot will be mixed sterilely to include at minimum 20cc calcium sulfate powder mixed with 1g of vancomycin powder and 1.2g of tobramycin powder per 10cc of calcium sulfate.

Intramedullary Calcium Sulfate Antibiotic Depot is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as STIMULAN for:

• Bone and soft tissue infections
• Osteomyelitis
• Musculoskeletal defects created by surgery, cyst, tumor, osteomyelitis or traumatic injury

Approved in United States as STIMULAN for:

• Bone voids or defects of the skeletal system created by surgery, cyst, tumor, osteomyelitis or traumatic injury

Approved in Canada as STIMULAN for:

• Bacterial infection in surrounding soft tissue

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

In a study involving 13 patients with long bone fracture-related infections, the use of a novel calcium sulphate-based local antibiotic delivery system resulted in a 100% infection remission rate over an average follow-up of 19.7 months.

All patients with unhealed fractures achieved bone union within an average of 8 months, demonstrating the efficacy and safety of this single-stage treatment protocol using the Stimulan Bullet Mat and Introducer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intramedullary application of local antibiotic bullets for the treatment of long bone fracture related infection. Patel, P., Iliadis, AD., Vris, A., et al.[2023]

The use of antibiotic-loaded calcium sulfate (CS) implants in the treatment of chronic osteomyelitis (COM) resulted in a high overall eradication rate of 92% across 16 studies involving 917 patients.

Postoperative complications were relatively low, with delayed wound healing being the most common issue, but the type of antibiotic used (tobramycin or vancomycin combined with gentamicin) did not significantly impact eradication rates or complication incidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic-loaded calcium sulfate in clinical treatment of chronic osteomyelitis: a systematic review and meta-analysis. Shi, X., Wu, Y., Ni, H., et al.[2022]

Fast-resorbing calcium sulfate pellets loaded with antibiotics can effectively deliver high local doses of medication to prevent infection in open fractures, dissolving within 12-16 hours and maintaining therapeutic levels against bacteria like P. aeruginosa and S. aureus.

In comparison to conventional calcium sulfate pellets, which take 4-6 days to dissolve and provide limited antibiotic efficacy, the new pellets show a significant advantage in rapidly inhibiting bacterial growth, suggesting they could be a valuable adjunctive therapy during surgical debridement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary in vitro evaluation of an adjunctive therapy for extremity wound infection reduction: rapidly resorbing local antibiotic delivery. Jackson, SR., Richelsoph, KC., Courtney, HS., et al.[2014]

In a study involving 15 patients with 17 comminuted open fractures, antibiotic-impregnated calcium sulfate was used successfully as a bone graft substitute, leading to clinical and radiographic evidence of fracture healing in 12 cases over an average follow-up of 8.5 months.

The use of this treatment reduced infection rates and assisted in fracture union, although 22.2% of patients required further surgical intervention for infection and 17.6% developed heterotopic ossification at the graft site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic-impregnated calcium sulfate use in combat-related open fractures. Helgeson, MD., Potter, BK., Tucker, CJ., et al.[2022]

Calcium sulphate is gaining popularity as a local antibiotic delivery system in orthopaedic and trauma surgery due to its advantages like predictable antibiotic release, quick biodegradation, and good biocompatibility, which help combat infections caused by antibiotic-resistant bacteria.

Current research and clinical use of calcium-sulphate-based products show promise in effectively treating and preventing surgical site and implant-associated infections, highlighting their potential as a valuable adjuvant therapy alongside traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of calcium-sulphate-based ceramics and synthetic bone substitutes used for antibiotic delivery in PJI and osteomyelitis treatment. Ene, R., Nica, M., Ene, D., et al.[2021]

In a study involving 106 patients treated for bone and joint infections, the use of local antibiotic-impregnated calcium sulphate beads resulted in a 95% success rate in controlling infections after surgical debridement.

The approach was found to be safe, with only 5.6% of patients experiencing severe complications, and no significant side effects reported from the calcium sulphate beads themselves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of Stimulan in bone and joint infections. Mereddy, P., Nallamilli, SR., Gowda, VP., et al.[2023]

In a study involving 72 New Zealand rabbits with MRSA-induced osteomyelitis, the combination of Stimulan (a synthetic calcium sulfate) and moxifloxacin significantly reduced bacterial growth compared to control and Stimulan-only groups.

The use of moxifloxacin-impregnated Stimulan not only led to lower bacterial counts but also resulted in greater fibrosis and inflammatory response, indicating its effectiveness in treating bone infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus with a synthetic carrier of calcium sulphate (Stimulan) releasing moxifloxacin. Kanellakopoulou, K., Galanopoulos, I., Soranoglou, V., et al.[2018]

In a study involving New Zealand white rabbits with Staphylococcus aureus infections, calcium sulfate pellets containing 10% tobramycin sulfate led to a significantly higher infection eradication rate (11 out of 13 rabbits) compared to other treatments, including debridement alone and placebo pellets.

The use of calcium sulfate as a biodegradable delivery system for tobramycin resulted in effective local antibiotic concentrations, peaking at 11.9 mg/ml in wound exudate on day 1, suggesting its potential as a targeted treatment for musculoskeletal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of experimental osteomyelitis by surgical debridement and the implantation of calcium sulfate tobramycin pellets. Nelson, CL., McLaren, SG., Skinner, RA., et al.[2022]

The novel calcium sulfate carrier effectively delivers high local concentrations of antibiotics (tobramycin and vancomycin) that are significantly above the minimum inhibitory concentration (MIC) needed to combat biofilm-related infections in periprosthetic joint infections (PJIs).

Serum concentrations of the antibiotics were largely undetectable, indicating that this delivery method minimizes the risk of systemic toxicity, making it a safe option for use in revision surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elution Profiles of Synthetic CaSO4 Hemihydrate Beads Loaded with Vancomycin and Tobramycin. Maale, GE., Eager, JJ., Mohammadi, DK., et al.[2021]

Citations

1. France pubmed.ncbi.nlm.nih.gov

Intramedullary application of local antibiotic bullets for the treatment of long bone fracture related infection. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Antibiotic-loaded calcium sulfate in clinical treatment of chronic osteomyelitis: a systematic review and meta-analysis. [2022]

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

Preliminary in vitro evaluation of an adjunctive therapy for extremity wound infection reduction: rapidly resorbing local antibiotic delivery. [2014]

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

Antibiotic-impregnated calcium sulfate use in combat-related open fractures. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Review of calcium-sulphate-based ceramics and synthetic bone substitutes used for antibiotic delivery in PJI and osteomyelitis treatment. [2021]

6. England pubmed.ncbi.nlm.nih.gov

The use of Stimulan in bone and joint infections. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus with a synthetic carrier of calcium sulphate (Stimulan) releasing moxifloxacin. [2018]

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

The treatment of experimental osteomyelitis by surgical debridement and the implantation of calcium sulfate tobramycin pellets. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Elution Profiles of Synthetic CaSO4 Hemihydrate Beads Loaded with Vancomycin and Tobramycin. [2021]