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

Trial Summary

What is the purpose of this trial?

There is currently no standard treatment to prevent burn depth conversion in partial-thickness burns. Conversion into deeper wounds is associated with higher complications and morbidity. The most common theory attributes this depth conversion to the prolonged inflammatory response that occurs after burn injury. Therefore, the investigators propose testing the safety and efficacy of tacrolimus ointment (an immunosuppressive agent) in patients with deep partial-thickness burns.

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.

What data supports the effectiveness of the drug Protopic® Ointment for treating burns?

Research shows that tacrolimus ointment (Protopic) is effective in treating skin conditions like atopic dermatitis and preventing rejection in skin grafts, suggesting it may help with healing and reducing inflammation in burns. ^{1 2 3 4 5}

Is Protopic® Ointment (Tacrolimus) generally safe for use in humans?

Protopic® Ointment (Tacrolimus) is generally safe for use in humans, with common side effects being a temporary burning sensation and itching at the application site. It does not cause skin thinning, making it safe for long-term use on all skin areas, including sensitive ones like the face. ^{1 2 3 6 7}

How is the drug Protopic® Ointment unique for treating burns?

Protopic® Ointment (tacrolimus) is unique because it is primarily used for skin conditions like atopic dermatitis and works by suppressing the immune response, which may help reduce inflammation in burns. Unlike standard burn treatments that focus on infection prevention and wound healing, tacrolimus targets the immune system to potentially reduce inflammation. ^{1 2 3 5 8}

Research Team

Wesley Thayer, MD, PhD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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.

Ability to implement treatment within 24-48 hours days of the initial burn

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

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

Long-term use of topical tacrolimus (FK506) in high-risk penetrating keratoplasty. [2013]

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

Topical tacrolimus ointment for treatment of intractable atopic keratoconjunctivitis: a case report and review of the literature. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Topical application of FK506 (tacrolimus) ointment inhibits mite antigen-induced dermatitis by local action in NC/Nga mice. [2017]

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

Effect of FK506 ointment (Protopic) on rat skin allograft model. [2014]

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

Tacrolimus ointment 0.03% for treatment of refractory childhood phlyctenular keratoconjunctivitis. [2013]

6. Canada pubmed.ncbi.nlm.nih.gov

Tacrolimus ointment (Protopic) for atopic dermatitis. [2014]

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

Tacrolimus pharmacology and nonclinical studies: from FK506 to protopic. [2021]

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

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