Antimicrobial Treatments for Frostbite

(Frostbite Trial)

Overseen By Tracey MacDermott

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must not be taking: Glycopeptide antibiotics

Disqualifiers: Pregnancy, Prisoners, CKD Stage IV/V, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which treatment better prevents infections from frostbite: aloe vera or long-acting silver dressings. It will also assess the safety and effectiveness of Dalbavancin, an antibiotic, for treating infections that develop from frostbite. Additionally, researchers will study how frostbite affects kidney processing of medications. Individuals with a recent frostbite injury or a confirmed or suspected infected frostbite wound, receiving treatment at the UCH Burn Center, might be suitable for this trial. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, helping to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have allergies to aloe, silver, or certain antibiotics like dalbavancin, you may not be eligible to participate.

What is the safety track record for these treatments?

Earlier studies have found Dalbavancin generally safe for treating skin and soft tissue infections. However, it can rarely cause ear damage, known as ototoxicity. Dalbavancin already has FDA approval for other uses, indicating its well-documented safety.

Research has shown that long-acting silver dressings are safe for short-term use on wounds, up to four weeks. These dressings are well-tolerated and effective in treating moderate wounds. Both treatments have good safety records, but discussing the benefits and risks with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard frostbite treatments, which typically involve warming and wound care, Dalbavancin offers a unique approach as an antibiotic given in a single intravenous dose. This method is particularly promising because it targets bacterial infections that can complicate frostbite, potentially reducing the need for prolonged antibiotic courses. Researchers are excited about Dalbavancin's long-acting properties, which might provide effective coverage with just one dose, simplifying treatment and improving patient compliance. Meanwhile, long-acting silver dressings provide sustained antimicrobial protection with fewer applications, and Aloe Vera offers a natural, soothing option applied directly to the skin. Each treatment brings a novel angle to managing frostbite, potentially enhancing outcomes and patient comfort.

What evidence suggests that this trial's treatments could be effective for frostbite?

Research has shown that dalbavancin, an antibiotic, effectively treats skin and other infections. One study found that 93% of patients were cured after using dalbavancin. In this trial, one group will receive a single 1500mg dose of dalbavancin intravenously. Another group will test long-lasting silver dressings, which have been found to help wounds heal faster and reduce infection rates. Studies indicate that these dressings can speed up healing and lower the risk of infection. Both treatments have shown promising results in fighting infections, which is important for treating frostbite injuries. ^{1 6 7 8 9}

Who Is on the Research Team?

Arek Wiktor, MD

Principal Investigator

University of Colorado Anschtuz

Are You a Good Fit for This Trial?

This trial is for individuals with frostbite who are at risk of infection. Participants must have sustained frostbite recently and be in a condition where they can receive the treatments being tested. Specific criteria about who can or cannot participate, such as age range, severity of frostbite, or other health conditions that might affect their participation, were not provided.

Inclusion Criteria

Aim 1: Admitted to UCH Burn Center with acute (within 4 days of cold exposure) frostbite injury

I am admitted to the UCH Burn center for a frostbite wound that is infected or suspected to be.

Exclusion Criteria

Anticipated death within 48 hours of admission

Inability to obtain consent from patient, legally authorized representative, or proxy

I was admitted for frostbite after five days, have an infection, or am allergic to aloe or silver.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Aloe Vera applied twice daily or Long-Acting Silver Dressings applied every 4 days to frostbitten tissues. Additionally, participants may receive a single 1500mg dose of Dalbavancin intravenously.

8 weeks

Multiple visits for wound culture assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including Dalbavancin concentration measurements and renal clearance evaluations.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dalbavancin

Trial Overview The study is testing the effectiveness of aloe vera versus long-acting silver wound dressings in preventing infections from frostbite injuries. Additionally, it's evaluating how well Dalbavancin—an FDA-approved antibiotic—treats those who develop infections and studying drug clearance from the body post-frostbite.

How Is the Trial Designed?

Group I: Aim 2: Dalbavancin Experimental Treatment 1 Intervention

Participants will receive one 1500mg dose of Dalbavancin intravenously.

Group II: Aim 1: Long-Acting Silver Dressings Experimental Treatment 1 Intervention

Long-Acting Silver dressings will be applied topically to participant's frostbitten tissues every 4 days.

Group III: Aim 1: Aloe Vera Active Control 1 Intervention

Aloe Vera will be applied topically to participant's frostbitten tissues twice daily.

Dalbavancin is already approved in United States for the following indications:

Approved in United States as Dalvance for:

• Acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible strains of Gram-positive microorganisms

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Congressionally Directed Medical Research Programs

Collaborator

Trials

59

Recruited

10,600+

Published Research Related to This Trial

Dalbavancin has shown an excellent safety profile in treating acute bacterial skin and skin structure infections (ABSSSI), with no significant differences in adverse events compared to other treatments in five Phase 3 clinical trials and additional studies.

It is a cost-effective option for patients with ABSSSI who might otherwise require hospitalization, although more extensive real-life studies are needed to fully understand its safety, particularly for rare adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: A Safety Profile of Dalbavancin for On- and Off-Label Utilization. Simonetti, O., Rizzetto, G., Molinelli, E., et al.[2022]

Dalbavancin, a new antibiotic for treating skin infections, shows high efficacy against gram-positive bacteria, with 99.6% of Staphylococcus aureus and 99.0% of beta-hemolytic streptococci being susceptible to it.

The study suggests that vancomycin susceptibility testing can reliably predict dalbavancin susceptibility, making it a useful surrogate until specific tests for dalbavancin are available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of vancomycin as a surrogate for dalbavancin in vitro susceptibility testing: results from the DISCOVER studies. Dunne, MW., Sahm, D., Puttagunta, S.[2022]

Dalbavancin demonstrated strong in vitro activity against a wide range of Gram-positive bacteria associated with infective endocarditis, showing 100% susceptibility against Staphylococcus aureus and high susceptibility rates for Enterococcus faecalis and viridans group streptococci.

The study analyzed 626 bacterial isolates from patients across the USA and Europe, indicating that dalbavancin has lower minimum inhibitory concentration (MIC) values compared to other antibiotics, suggesting it could be a potent option for treating this serious infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial activity of dalbavancin tested against Gram-positive organisms isolated from patients with infective endocarditis in US and European medical centres. Sader, HS., Mendes, RE., Pfaller, MA., et al.[2020]

In a study of 125 adult patients treated with dalbavancin for acute bacterial skin infections in a rural emergency department, only 12.8% were admitted to the hospital within 30 days, indicating that dalbavancin is effective in reducing hospital admissions after treatment.

Despite the low admission rate, 30-day readmission was notably higher among patients with certain conditions like abnormal white blood cell counts, congestive heart failure, hypertension, and diabetes, suggesting that these factors may influence treatment outcomes and the need for tailored local treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world utilization of Dalbavancin at a rural community emergency department. Dolan, A., Kuge, E., Bremmer, E., et al.[2022]

Dalbavancin is a potent new antibiotic that shows greater in vitro effectiveness than vancomycin against various bacteria, including Staphylococcus aureus and Enterococcus spp., making it a promising treatment for serious infections.

In clinical trials, dalbavancin demonstrated comparable efficacy to established antibiotics like linezolid and vancomycin for treating complicated skin infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalbavancin, a long-acting lipoglycopeptide for the treatment of multidrug-resistant Gram-positive bacteria. Decousser, JW., Bourgeois-Nicolaos, N., Doucet-Populaire, F.[2014]

In a study involving 39 patients with uncomplicated S. aureus bacteremia, dalbavancin demonstrated a 100% clearance rate of the bloodstream infection, outperforming the 95% clearance rate seen in patients treated with comparators like vancomycin or linezolid.

Dalbavancin also showed a high clinical success rate of 92% at the end of treatment, comparable to the 78% success rate of the comparator therapies, indicating its efficacy as a treatment option for serious bacterial infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in Patients with Staphylococcus aureus Bacteremia Treated with Dalbavancin in Clinical Trials. Gonzalez, PL., Rappo, U., Akinapelli, K., et al.[2022]

Dalbavancin is an effective antibiotic for treating acute bacterial skin and skin-structure infections caused by Gram-positive bacteria, and it has been in use since 2014 in the USA and 2015 in the EU.

In clinical practice, dalbavancin is also beneficial for treating complex infections related to cardiac devices and prosthetics, particularly when biofilm formation is a concern, suggesting its versatility in managing hard-to-treat infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current trends in the real-life use of dalbavancin: report of a study panel. Durante-Mangoni, E., Gambardella, M., Iula, VD., et al.[2021]

In a study of 23 patients (22 with bacteremia and 1 with endocarditis), Dalbavancin was effective in clearing infections, with all 22 patients showing confirmed culture clearance and no reported side effects.

The results suggest that Dalbavancin could be a safe and effective outpatient treatment option for patients unable to undergo prolonged hospitalization, as there were no readmissions or deaths related to the infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful use of dalbavancin in the treatment of gram positive blood stream infections: a case series. Evins, C., Lancaster, H., Schnee, AE.[2022]

Dalbavancin, an antibiotic effective against skin and soft tissue infections, was used off-label in a 55-year-old man for a prosthetic joint infection, but it led to a rare case of bilateral sensorineural hearing loss after a cumulative dose of 2500 mg.

This case underscores the need for caution when using dalbavancin beyond its approved dosing guidelines, as it may pose risks such as ototoxicity, highlighting the importance of monitoring patients closely during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ototoxicity associated with extended dalbavancin treatment for a shoulder prosthetic joint infection. Lange, A., Thunberg, U., Söderquist, B.[2023]

Dalbavancin is an effective antibiotic for treating acute bacterial skin infections, particularly against gram-positive bacteria like MRSA, with a much lower minimum inhibitory concentration than most other MRSA treatments.

Its extended half-life allows for a convenient dosing schedule of just two doses over a week, making it a practical option compared to traditional antibiotics like vancomycin, while showing similar efficacy in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalbavancin: A Novel Lipoglycopeptide Antibiotic with Extended Activity Against Gram-Positive Infections. Smith, JR., Roberts, KD., Rybak, MJ.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06266494

Prevention and Treatment of Frostbite Infection With ... The investigators will also study the safety and effectiveness of Dalbavancin, an FDA approved antibiotic used for treating people who develop frostbite ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9501058/

Clinical Effectiveness and Pharmacokinetics of ... This work aimed to study the clinical effectiveness and tolerability of DBV in outpatients with ABSSSIs, osteoarticular (OA), or other infections.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9726471/

Clinical outcomes following dalbavancin administration in ... Median antibiotic duration prior to dalbavancin administration was 7 days. Within 90 days, 93% achieved clinical cure, 12% were readmitted, 12% developed ...

4. mdpi.com mdpi.com/2079-6382/13/11/1063

Safety and Efficacy of Dalbavancin in Real Life Results: A total of 100 patients treated with dalbavancin and followed up for 6 months after treatment (58% male; median age 63.5 years, median Charlson ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8059686/

Dalbavancin Efficacy and Impact on Hospital Length-of-Stay ... The study aimed to evaluate the impact of dalbavancin therapy on both hospital length-of-stay (LOS) and treatment-related costs, as well as to describe the ...

6. trial.medpath.com trial.medpath.com/clinical-trial/660be8723ad99de9/nct06266494-prevention-treatment-frostbite-infection-antimicrobial

Prevention and Treatment of Frostbite Infection ... - MedPath The investigators will also study the safety and effectiveness of Dalbavancin, an FDA approved antibiotic used for treating people who develop frostbite ...

7. withpower.com withpower.com/trial/phase-4-frostbite-1-2024-6a08c

Antimicrobial Treatments for Frostbite Dalbavancin is generally considered safe for treating skin and soft tissue infections, but there is a rare case of ototoxicity (ear damage) reported with ...

8. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT06266494?keyword=%22Frostbite%22

Prevention and Treatment of Frostbite Infection With ... The investigators will also study the safety and effectiveness of Dalbavancin, an FDA approved antibiotic used for treating people who develop frostbite ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39596758/

Safety and Efficacy of Dalbavancin in Real Life The overall clinical success rate was 84%-91% for registered and 82% for unregistered indications. The prescription of higher loading doses was ...