Protopic® Ointment for Burns

Overseen By Julia Yao, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vanderbilt University Medical Center

Must not be taking: Tacrolimus, Bacitracin

Disqualifiers: Pregnancy, Immunosuppression, Incarceration, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of tacrolimus ointment (also known as Protopic® or Tacrus) for individuals with deep partial-thickness burns on their hands. The goal is to prevent these burns from worsening, as deeper burns can lead to more complications. Participants will receive either the tacrolimus ointment, bacitracin ointment, or a hydrocolloid dressing after standard wound cleaning. Those with deep partial-thickness burns on their hands from sources like fire or hot liquids, who have not received other treatments, may find this trial suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this 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. However, if you are on medications that cause immunosuppression or require aggressive treatment for infections, you may not be eligible to participate.

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

Previous studies have used tacrolimus ointment to treat skin conditions like eczema. Patients generally tolerate it well. Common side effects include a burning or stinging sensation at the application site, which are usually mild and resolve on their own.

Avoid using the ointment on open cuts or scrapes, and those allergic to tacrolimus should not use it. The FDA has approved this ointment for other skin issues, indicating its relative safety. Consult a doctor if there are concerns about side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for burns?

Unlike the standard burn treatments, which often involve antibiotics like bacitracin, Tacrolimus Ointment 0.03% is unique because it uses an immunosuppressant to potentially reduce inflammation and improve healing. This ointment works differently by targeting the immune response, which could lead to faster recovery times and better outcomes for burn patients. Researchers are excited about Tacrolimus Ointment because its novel mechanism might offer a more effective way to manage burns compared to traditional antibiotic ointments.

What evidence suggests that tacrolimus ointment might be an effective treatment for burns?

This trial will compare Tacrolimus Ointment 0.03% with hydrocolloid dressing to other burn treatments. Research has shown that tacrolimus ointment can help with skin problems. It has been particularly effective in treating atopic dermatitis, a common form of eczema, and outperforms standard hydrocortisone treatments. Large studies demonstrated that tacrolimus ointment improved skin conditions without introducing new safety issues. For burns, tacrolimus may help by reducing inflammation, which is crucial to prevent worsening. Early results from burn studies suggest it can reduce symptoms like burning and redness, indicating its potential usefulness for treating deeper burns by managing inflammation. ^{5 6 7 8 9}

Who Is on the Research Team?

Wesley Thayer, MD, PhD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for men and women aged 50-75 with deep partial-thickness burns on their hands, covering ≤5% of their body. They must be able to start treatment within 24-48 hours after the burn and commit to the study's duration. Exclusions include pregnancy, breastfeeding, certain infections or conditions that affect safety/data quality, immunosuppression, prior treatments or studies involving the burn wound(s), allergies to tacrolimus or bacitracin.

Inclusion Criteria

For females of reproductive potential, confirmed negative urine pregnancy test at enrollment

I am between 50 and 75 years old.

Provision of signed and dated informed consent form by the subject or Legally Authorized Representative

Exclusion Criteria

I have not participated in any burn wound studies in the last 60 days.

My burn is caused by friction, chemicals, or electricity.

Subject is incarcerated

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tacrolimus ointment or other standard treatments for deep partial-thickness burns

3 weeks

Weekly visits for wound assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tacrolimus Ointment

Trial Overview The trial tests Tacrolimus ointment's effectiveness in preventing deepening of partial-thickness burns. The goal is to see if this immunosuppressive agent can reduce complications by managing inflammation after a burn injury.

How Is the Trial Designed?

Group I: Tacrolimus Ointment 0.03% with hydrocolloid dressing Experimental Treatment 1 Intervention

Standard out-patient wound cleaning followed by application of tacrolimus ointment over the burn and hydrocolloid dressing on the treated area.

Group II: Bacitracin ointment Active Control 1 Intervention

Standard out-patient wound cleaning followed by application of bacitracin ointment over the burn and hydrocolloid dressing on the treated area.

Group III: Hydrocolloid dressing Active Control 1 Intervention

Standard out-patient wound cleaning followed by application of hydrocolloid dressing on the burned area.

Tacrolimus Ointment is already approved in United States for the following indications:

Approved in United States as Protopic for:

• Moderate to severe atopic dermatitis in non-immunocompromised adults and children aged 2 to 15 years

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Tacrolimus 0.03% ointment was successfully used to treat a 32-year-old man with severe atopic keratoconjunctivitis that had not responded to multiple previous treatments, leading to symptom resolution and a decrease in giant papillae size after 2 months.

The treatment was well-tolerated with no reported side effects, and the patient remained asymptomatic for 8 months after completing the therapy, suggesting that tacrolimus may be a safe and effective alternative for refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical tacrolimus ointment for treatment of intractable atopic keratoconjunctivitis: a case report and review of the literature. García, DP., Alperte, JI., Cristóbal, JA., et al.[2022]

Topical tacrolimus 0.03% ointment effectively managed acute rejection episodes in all 4 high-risk corneal transplant patients over a mean follow-up of 33 months, with no further graft rejections observed during treatment.

The treatment was well-tolerated with no adverse effects reported, suggesting that tacrolimus can be a safe and effective second-line immunosuppressive option for patients who have failed traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term use of topical tacrolimus (FK506) in high-risk penetrating keratoplasty. Dhaliwal, JS., Mason, BF., Kaufman, SC.[2013]

Tacrolimus, originally used to prevent organ rejection in transplants, has been successfully developed into an ointment for treating atopic dermatitis, demonstrating its versatility as an immunomodulator.

The approval of 0.03% and 0.1% tacrolimus ointment (Protopic) as a first-in-class treatment was supported by extensive nonclinical pharmacology and toxicology studies, ensuring its safety and efficacy for patients with atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus pharmacology and nonclinical studies: from FK506 to protopic. Bekersky, I., Lilja, H., Lawrence, I.[2021]

Topical tacrolimus 0.03% ointment was effective in treating two cases of refractory phlyctenular keratoconjunctivitis in children, showing improvement within a week and complete resolution after three weeks.

The treatment was well-tolerated with no reported side effects, suggesting that tacrolimus can be a safe alternative for patients who do not respond to corticosteroids and other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus ointment 0.03% for treatment of refractory childhood phlyctenular keratoconjunctivitis. Kymionis, GD., Kankariya, VP., Kontadakis, GA.[2013]

FK506 ointment effectively suppresses dermatitis in a mouse model of atopic dermatitis by reducing local inflammatory markers like IL-4 and IFN-gamma, indicating its therapeutic potential.

The treatment works locally without causing systemic immune suppression, which is important for maintaining overall immune function while managing skin inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical application of FK506 (tacrolimus) ointment inhibits mite antigen-induced dermatitis by local action in NC/Nga mice. Sasakawa, T., Higashi, Y., Sakuma, S., et al.[2017]

In a study of 11 patients with severe atopic keratoconjunctivitis (AKC), 0.1% tacrolimus ointment showed significant improvement in symptoms and signs within one week, with nearly all patients achieving complete resolution by six weeks.

Tacrolimus ointment was well-tolerated, with no serious side effects reported, and it may serve as a safe alternative to steroid treatments for managing refractory AKC, as eight patients remained symptom-free for up to three years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of tacrolimus ointment for treatment of atopic keratoconjunctivitis. Al-Amri, AM.[2014]

Tacrolimus ointment is a safe and effective treatment for atopic dermatitis in both children and adults, working by inhibiting calcineurin to reduce T-cell activation and inflammation.

Unlike topical corticosteroids, tacrolimus does not cause skin thinning or atrophy, allowing for long-term use on sensitive areas like the face without the risk of adverse effects associated with corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus ointment (Protopic) for atopic dermatitis. Pascual, JC., Fleisher, AB.[2014]

FK-506 ointment (Protopic) therapy demonstrated a comparable ability to prolong skin graft survival (16.7 days) compared to intravenous FK-506 (Prograf) injection (15.8 days) in a rat model, suggesting its efficacy in preventing allograft rejection.

The ointment resulted in significantly lower blood levels of tacrolimus (<0.2 ng/mL) compared to the injection (0.45 ng/mL), indicating a potentially safer option with reduced systemic exposure while maintaining similar immunosuppressive effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of FK506 ointment (Protopic) on rat skin allograft model. Kim, YE., Eun, SC.[2014]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05856994

Clinical Assessment of Protopic® Ointment in Deep Partial- ... This study is a randomized clinical trial of the usage of tacrolimus ointment for the treatment of deep partial-thickness burns with comprehensive assessments ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3047937/

Topical tacrolimus as treatment of atopic dermatitis - PMC Both 0.03% and 0.1% tacrolimus ointments were significantly more effective than 1% hydrocortisone acetate when applied for 3 weeks in children. The efficacy of ...

3. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/422043

Effect of Oral Acetylsalicylic Acid on Burning Caused by ... All patients experienced significantly less burning of the skin after tacrolimus treatment with aspirin therapy. Three patients reported no burning, while 3 ...

4. medicaljournals.se medicaljournals.se/acta/content/html/10.2340/00015555-2699

Disrupted Skin Barrier is Associated with Burning ... In general, the burning sensation, pruritus and erythema resolve within one week of initiating topical tacrolimus and occur more frequently in ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0190962205013460

Tacrolimus ointment is safe and effective in the treatment of ... Tacrolimus ointment monotherapy in almost 8000 pediatric and adult patients led to continuous improvement in AD and revealed no change in the safety profile.

6. mayoclinic.org mayoclinic.org/drugs-supplements/tacrolimus-topical-route/description/drg-20068159

Tacrolimus (topical route) - Side effects & dosage Do not use on skin areas that have cuts or scrapes. If it does get on ... burning or stinging sensation of the face; change in size, shape, or color of ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/050777s018lbl.pdf

Protopic (tacrolimus) label - accessdata.fda.gov PROTOPIC (tacrolimus) Ointment is contraindicated in patients with a history of hypersensitivity to tacrolimus or any other component of the ointment. WARNINGS.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7992708/

Incidence of Topical Tacrolimus Adverse Effects in Chronic ... The incidence of burning sensation after application of 0.1% tacrolimus was 19%~59%, followed by pruritus. However, these are generally transient and have mild ...

9. webmd.com webmd.com/drugs/2/drug-20330/tacrolimus-topical/details

Tacrolimus topical (Protopic) – Uses, Side Effects, and More What are the most common side effects of topical tacrolimus? · Burning, tingling, itching, soreness, or redness where it is applied · Acne ...