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?

This trial explores a new treatment to prevent infections in people with open fractures of the lower leg. Researchers compare a special calcium sulfate antibiotic mix (Intramedullary Calcium Sulfate Antibiotic Depot) with usual care to determine its effectiveness in stopping infections. Individuals with a type II or III open tibia fracture requiring intramedullary nail fixation may qualify for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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

Research shows that a special treatment using calcium sulfate with antibiotics, designed for open leg bone fractures, looks promising in fighting infections. This treatment delivers antibiotics directly into the bone, helping to kill bacteria and stop them from growing. This is important for healing fractures without complications.

In animal studies, these calcium sulfate antibiotics effectively cleared infections and reduced the formation of biofilms, protective layers that bacteria create to shield themselves from antibiotics. This suggests the treatment might work well in humans too.

Additionally, research has shown high success rates in patients treated with this type of antibiotic along with standard antibiotics. Most patients experienced healing of their fractures, and infections were kept under control.

While the treatment looks promising, it's important to know that researchers are still testing it for safety and effectiveness in humans. The current trial phase suggests some evidence of safety, but more information is being gathered to confirm this. Always consult with a healthcare provider to discuss potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the intramedullary calcium sulfate antibiotic depot because it offers a novel approach to treating open tibia fractures. This treatment combines calcium sulfate with antibiotics like vancomycin and tobramycin, allowing for localized drug delivery directly to the fracture site. Unlike standard treatments that rely solely on surgical hardware like intramedullary nails, this depot can potentially reduce infection rates by delivering antibiotics precisely where they are needed. This targeted delivery could lead to faster healing and fewer complications, making it a promising alternative to current care options.

What evidence suggests that the intramedullary calcium sulfate antibiotic depot is effective for preventing infection in open tibia fractures?

Research shows that using a calcium sulfate antibiotic depot inside the bone may help prevent infections in open leg fractures. In this trial, one group of participants will receive the intramedullary calcium sulfate antibiotic depot before intramedullary nailing. Studies have found that calcium sulfate with antibiotics can treat infections, suggesting it might also prevent them. In a study of patients with fractures that weren't healing, 93.3% experienced bone healing after receiving a similar calcium sulfate treatment. This indicates that the treatment might not only prevent infections but also aid in bone healing. Overall, these findings suggest that placing an antibiotic depot in the bone could help prevent infections in open leg fractures. ^{1 4 6 7 8}

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

Hypercalcemia

No email, phone, or other point of contact

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 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]

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 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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10134749/

The efficacy of antibiotic-impregnated calcium sulfate ... Of the 80 non-union patients who received OSTEOSET®-T, 93.3 % achieved bony union at an average time of 6.9 months. The 74 non-union patients who received ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05766670/intramedullary-calcium-sulfate-antibiotic-depot

Intramedullary Calcium Sulfate Antibiotic Depot This research is a randomized clinical trial aimed to reduce the frequency of fracture related infections following open tibia fracture.

3. journals.lww.com journals.lww.com/jorthotrauma/fulltext/2021/08000/intramedullary_antibiotic_depot_does_not_preclude.16.aspx

Intramedullary Antibiotic Depot Does Not Preclude... We present a technique of IM lengthening or compression using a nail plus IM antibiotic delivery with an absorbable calcium sulfate depot.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05766670

Intramedullary Calcium Sulfate Antibiotic Depot This research is a randomized clinical trial aimed to reduce the frequency of fracture related infections following open tibia fracture. The proposed test ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7594263/

Intramedullary reaming and irrigation and antibiotic-loaded ... Intramedullary nail removal, medullary reaming and irrigation, and antibiotic-loaded calcium sulfate implantation seems effective in the treatment of infection ...

6. trialx.com trialx.com/clinical-trials/listings/296099/intramedullary-calcium-sulfate-antibiotic-depot/

Intramedullary Calcium Sulfate Antibiotic Depot This prospective randomized clinical trial will compare outcomes between patients treated with an antibiotic depot placed inside the bone at ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8253503/

Intramedullary Antibiotic Depot Does Not Preclude ... Calcium sulfate delivered antibiotics have been shown to eradicate osteomyelitis in animal infection models and reduce immature biofilm formation in vitro.

8. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05766670/

Trial | NCT05766670 This prospective randomized clinical trial will compare outcomes between patients treated with an antibiotic depot placed inside the bone at the time of final ...