Vancomycin Powder for Fractures

(POWDER Trial)

Recruiting at 1 trial location

Overseen By Robert A De Lorenzo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: High-potency antibiotics

Disqualifiers: Pregnancy, Prisoners, Others

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

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: 1

Duration: Immediate (single application)

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This is the first prospective controlled study to determine whether the topical application of vancomycin powder reduces infection-related complications when applied to open fracture injuries in the acute emergency department setting.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are using a high-potency antibiotic powder or solution on your wound, you may not be eligible to participate.

What data supports the effectiveness of the drug Vancomycin Powder for treating fractures?

Research shows that using vancomycin powder can reduce the risk of infections after surgery, including in fractures and other surgeries, by lowering the presence of harmful bacteria like Staphylococcus aureus. ^{1 2 3 4 5}

Is vancomycin powder safe for use in humans?

Vancomycin powder has been shown to be safe in children and is used to treat serious infections. However, it can cause side effects like ototoxicity (hearing damage) if blood levels are too high. ^{2 6 7 8 9}

How is the drug Vancomycin Powder unique for treating fractures?

Vancomycin Powder is unique because it is applied directly to the surgical site during fracture surgery, which helps reduce the risk of infection, particularly from Staphylococcus aureus, without causing significant side effects like nephrotoxicity (kidney damage). This local application is different from traditional systemic antibiotic treatments that are taken orally or injected. ^{2 10 11 12 13}

Research Team

Robert A De Lorenzo, MD

Principal Investigator

University of Texas

Eligibility Criteria

Adults over 18 with open fractures of certain bones who can consent to the study within 24 hours of injury. Excluded are those treated with high-potency antibiotics, allergic to vancomycin, pregnant women, prisoners, and subjects already operated on for the fracture elsewhere.

Inclusion Criteria

I have an open fracture in one of my major bones.

I am 18 years old or older.

My injury occurred less than 24 hours ago.

Exclusion Criteria

Time from injury > 24 hours.

I had surgery for an open fracture at another hospital.

I do not speak English or Spanish.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive usual care plus topical application of 2 grams of vancomycin powder to open fracture wounds in the emergency room

Immediate (single application)

1 visit (in-person)

Follow-up

Participants are monitored for infection-related complications and other outcomes

12 months

Multiple visits as needed for monitoring

Treatment Details

Interventions

• Vancomycin

Trial Overview The trial is testing if applying vancomycin powder directly into open fractures in the emergency room can reduce infection-related complications compared to not using it or standard treatments.

Participant Groups

Group I: Intervention Arm Experimental Treatment 1 Intervention

Subjects randomized to the Intervention Arm will receive usual care plus two (2) grams of Vancomycin powder administered topically. In the emergency room prior to surgical intervention, a qualified member of the study team or clinical team member will apply 2 grams of vancomycin powder directly to the open fracture site such that all visible surfaces of the wound are completely and uniformly covered, including bone edges.

Group II: Observational Arm Active Control 1 Intervention

Subjects who otherwise meet the criteria to be included in the study but are not able to provide consent, either themselves or through a Legally Authorized Representative, will be placed in the Observational Arm and receive usual care with no experimental intervention.

Group III: Control Arm Active Control 1 Intervention

Subjects randomized to the Control Arm will receive usual care for open long bone fracture as determined by the treating physician.

Vancomycin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Vancocin for:

• Severe infections caused by susceptible strains of methicillin-resistant staphylococci
• Enterocolitis caused by Staphylococcus aureus
• Staphylococcal endocarditis

Approved in European Union as Vancomycin for:

• Severe infections caused by Gram-positive bacteria
• Endocarditis
• Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD)

Approved in Canada as Vancomycin for:

• Severe infections caused by susceptible strains of methicillin-resistant staphylococci
• Enterocolitis caused by Staphylococcus aureus

Approved in Japan as Vancomycin for:

• Severe infections caused by Gram-positive bacteria
• Endocarditis

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

United States Army Institute of Surgical Research

Collaborator

Trials

30

Recruited

1,800+

San Antonio Military Medical Center

Collaborator

Trials

22

Recruited

4,800+

Findings from Research

In a review of 16 studies involving 2,171 cases of uninstrumented spine surgery, the use of intra-wound vancomycin powder did not significantly reduce the overall rate of surgical site infections (SSI) compared to controls, with infection rates of 1.26% for vancomycin and 1.45% for controls.

However, in specific studies with higher baseline infection rates, vancomycin showed a significant reduction in infections, suggesting it may be beneficial in high-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical site infection prophylaxis with intra-wound vancomycin powder for uninstrumented spine surgeries: a meta-analysis. Zale, C., Nicholes, M., Hu, S., et al.[2023]

In a study of 143 patients with surgical site infections after fracture surgery, those who received topical vancomycin powder had a significantly lower rate of Staphylococcus aureus infections (10%) compared to those who did not receive it (50%).

The use of vancomycin powder may change the bacteriology of infections, potentially reducing the presence of methicillin-resistant Staphylococcus aureus, although further research in larger trials is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Vancomycin Powder Decreases the Proportion of Staphylococcus aureus Found in Culture of Surgical Site Infections in Operatively Treated Fractures. Qadir, R., Costales, T., Coale, M., et al.[2021]

A case study of a 62-year-old woman revealed that vancomycin powder, while effective in reducing surgical site infections, can cause serious complications such as surgical drain occlusion, which occurred post-surgery in this patient.

The obstruction was due to vancomycin powder residue in the drain, leading to a lack of drainage and potential risks like epidural hematoma; this highlights the need for careful management of antibiotic powders in surgical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drain blockage by topical vancomycin powder-a case report of a potentially catastrophic complication in spine surgery. Shea, GK.[2023]

The POWDER study is a multicenter clinical trial involving 200 patients with open long bone fractures, aiming to evaluate the efficacy of topical vancomycin powder in preventing infections when applied within 24 hours of injury.

If effective, topical vancomycin could serve as a simple and cost-effective method to reduce infection rates in open fractures, which are currently high in both military and civilian contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placement of Antibiotic Powder in Open Fracture Wounds during the Emergency Room (POWDER): Design and Rationale for an Investigation of the Acute Application of Topical Antibiotic Powder in Open Fracture Wounds for Infection Prophylaxis. Wheeler, AR., Burbank, KM., April, MD., et al.[2023]

In a study of 419 patients undergoing deep brain stimulation surgery, the use of vancomycin powder significantly reduced the rate of postoperative surgical site infections (SSIs) from 3.1% to 0.38%.

No complications were associated with the use of vancomycin powder, suggesting it is a safe and effective adjunct to standard antibiotic prophylaxis in DBS surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Utility of Vancomycin Powder in Reducing Surgical Site Infections in Deep Brain Stimulation Surgery. Kochanski, RB., Nazari, P., Sani, S.[2019]

In a study of 228 patients with orthopedic infections, transitioning from parenteral vancomycin to oral antibiotics significantly reduced the rate of adverse drug events (ADE), with 5.87 ADE per 1000 patient-days on vancomycin compared to only 1.49 ADE per 1000 patient-days on oral therapy.

Patients who switched to oral therapy within 4 weeks did not experience higher rates of unplanned hospital readmissions or treatment failures, suggesting that oral antibiotics can effectively minimize toxicity while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching from intravenous vancomycin to oral antibiotics reduces adverse events in a retrospective cohort of outpatients with orthopedic infections. Gallagher, CK., Cummins, H., Benefield, RJ., et al.[2023]

A retrospective study of 36 patients undergoing 191 procedures for early-onset scoliosis found that using vancomycin powder significantly reduced the rate of surgical site infections (SSIs) from 13.8% in the control group to 4.8% in the vancomycin group (p = 0.038).

The study suggests that vancomycin powder is effective in preventing SSIs in growing spine surgery, with an estimated 10.9 procedures needed to prevent one infection, indicating its potential as a safe and beneficial intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Vancomycin Powder Decrease Surgical Site Infections in Growing Spine Surgery?: A Preliminary Study. Thompson, GH., Poe-Kochert, C., Hardesty, CK., et al.[2022]

Vancomycin is an effective antibiotic for treating serious staphylococcal infections, especially when other antibiotics like penicillins and cephalosporins cannot be used, making it a crucial alternative therapy.

While vancomycin is generally safe, it can cause ototoxicity if serum levels exceed 30 micrograms/ml, highlighting the importance of monitoring drug levels during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin. Hermans, PE., Wilhelm, MP.[2019]

Vancomycin is regaining attention due to its effectiveness against resistant gram-positive bacteria and improvements in its drug purity, making it a valuable option in treating infections.

The review highlights vancomycin's antimicrobial activity, pharmacokinetics, clinical uses, dosing regimens, and potential side effects, providing a comprehensive overview for healthcare professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin. A new old agent. Ingerman, MJ., Santoro, J.[2013]

In a study of 58 patients undergoing fracture surgery, the use of topical vancomycin powder did not result in detectable serum levels of vancomycin, indicating low systemic absorption.

The application of topical vancomycin powder was not associated with nephrotoxicity, as most patients showed no significant increase in serum creatinine levels post-surgery, suggesting it is a safe option for preventing infections in orthopedic procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Absorption and Nephrotoxicity Associated With Topical Vancomycin Powder for Fracture Surgery. O'Toole, RV., Degani, Y., Carlini, AR., et al.[2022]

This phase III clinical trial aims to evaluate the effectiveness of local vancomycin powder in preventing surgical site infections (SSIs) after fracture surgery, specifically in patients with tibial plateau or pilon fractures, involving a total of 1000 participants (500 per treatment group).

The study will not only assess the rate of deep SSIs six months post-surgery but also analyze bacterial species and their susceptibilities, potentially leading to a better understanding of infection risks and improved prevention strategies in orthopedic trauma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter, Randomized, Controlled Trial (VANCO Study). OʼToole, RV., Joshi, M., Carlini, AR., et al.[2022]

Locally administered vancomycin powder achieves significantly higher concentrations in surrounding soft tissues and bone compared to systemic intravenous dosing, with peak concentrations occurring at 4 hours post-administration.

The effective local delivery of vancomycin lasts for about 48 hours, after which the drug levels drop rapidly to undetectable levels, suggesting a potential for effective prophylaxis against surgical site infections in the early post-operative period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone penetrance of locally administered vancomycin powder in a rat femur fracture model. Working, ZM., Frederiksen, H., Drew, A., et al.[2022]

In a study of 289 patients undergoing posterior cervical fusion surgeries, the use of local vancomycin powder did not significantly reduce the rate of deep wound infections compared to those who did not receive the treatment (5.2% vs. 6.9%).

Logistic regression analysis confirmed that the application of vancomycin powder had no meaningful impact on the development of surgical site infections, suggesting that its routine use may not be effective in preventing infections in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with intrawound vancomycin powder for posterior cervical fusion surgery. Martin, JR., Adogwa, O., Brown, CR., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Surgical site infection prophylaxis with intra-wound vancomycin powder for uninstrumented spine surgeries: a meta-analysis. [2023]

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

Topical Vancomycin Powder Decreases the Proportion of Staphylococcus aureus Found in Culture of Surgical Site Infections in Operatively Treated Fractures. [2021]

3. China pubmed.ncbi.nlm.nih.gov

Drain blockage by topical vancomycin powder-a case report of a potentially catastrophic complication in spine surgery. [2023]

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

Placement of Antibiotic Powder in Open Fracture Wounds during the Emergency Room (POWDER): Design and Rationale for an Investigation of the Acute Application of Topical Antibiotic Powder in Open Fracture Wounds for Infection Prophylaxis. [2023]

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

The Utility of Vancomycin Powder in Reducing Surgical Site Infections in Deep Brain Stimulation Surgery. [2019]

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

Switching from intravenous vancomycin to oral antibiotics reduces adverse events in a retrospective cohort of outpatients with orthopedic infections. [2023]

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

Does Vancomycin Powder Decrease Surgical Site Infections in Growing Spine Surgery?: A Preliminary Study. [2022]

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

Vancomycin. [2019]

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

Vancomycin. A new old agent. [2013]

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

Systemic Absorption and Nephrotoxicity Associated With Topical Vancomycin Powder for Fracture Surgery. [2022]

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

Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter, Randomized, Controlled Trial (VANCO Study). [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Bone penetrance of locally administered vancomycin powder in a rat femur fracture model. [2022]

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

Experience with intrawound vancomycin powder for posterior cervical fusion surgery. [2022]