Clinical Assessment of Protopic® Ointment in Deep Partial-Thickness Burns

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.

Study Overview

• Status: Recruiting
• Conditions: Burn Injury
• Intervention / Treatment: Drug: Tacrolimus ointment

Detailed Description

Patients who sustain burn injuries are some of the most complex patients to care for, often requiring a multidisciplinary team of providers specialized in burn pathophysiology. While many facets of burn care must be accounted for including fluid management, nutrition, respiratory status, immunologic and cardiovascular function, innovation in the treatment for deep partial thickness burns is of paramount importance.

Burn depth conversion is a phenomenon where superficial partial-thickness burns spontaneously convert into deep partial-thickness or full-thickness burns, which are associated with higher complications and morbidity. The most common theory attributes this depth conversion to the prolonged inflammatory response that occurs after burn injury. Excess inflammation worsens the injury through various mechanisms, including cytokine production, delayed inflammatory cell apoptosis, and reactive oxidative species production.

Protopic® (tacrolimus) Ointment is a macrolide immunosuppressant and a calcineurin inhibitor. Tacrolimus inhibits T-lymphocyte activation, a key cell in the body's immune response. A prolonged inflammatory response is theorized to contribute to a worse recovery outcome in partial- to full-thickness burns. Therefore, tacrolimus possesses properties that could slow the acute inflammatory response and potentially improve clinical outcomes in deep partial-thickness burns. There has yet to be a clinical study to investigate the use of tacrolimus in burn treatment. However, our group recently published an animal study that found a significant reduction in burn depth using tacrolimus topically (White-Dzuro et al. Burns 2022). This study is a randomized clinical trial of the usage of tacrolimus ointment for the treatment of deep partial-thickness burns with comprehensive assessments of healing and functional outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wesley Thayer, MD, PhD; Phone Number: 6159360160; Email: wesley.thayer@vumc.org
• Study Contact Backup: Name: Julia Yao, BSN; Phone Number: 6153438426; Email: jun.yao@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form by the subject or Legally Authorized Representative.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female aged 50 to 75 at time of screening visit.
• For females of reproductive potential, confirmed negative urine pregnancy test at enrollment.
• Presence of deep partial-thickness burns to one or both dorsal hands (burns may be present on other areas of the body, so long as all regions combined are ≤ 5% Total Body Surface Area [TBSA], using the Browder and Lund Chart).
• Thermal burn (caused by fire, hot objects, steam or hot liquids [scalding]) etiology, located on one or both dorsal hands.
• Ability to implement treatment within 24-48 hours days of the initial burn.

Exclusion Criteria:

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study, if applicable.
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Allergy or hypersensitivity to tacrolimus or other components of the ointment (per subject report) or personal preference.
• Allergy or hypersensitivity to bacitracin and/or any of its drug formulation components. Patients with known hypersensitivity to neomycin may also be sensitive to bacitracin.
• Subject is incarcerated.
• Friction, chemical or electric burn etiology.
• Immunosuppression, as determined by the Principal Investigator.
• Presence of a local and/or systemic infection that, in the Investigator's opinion, requires aggressive treatment which would warrant exclusion from participating in this study.
• Subject is unwilling or unable to follow study related procedures and/or follow-up visits.
• Prior treatment to the burn wound(s) on the hand(s) considered for this trial with another product (treatment failure).
• Subject report of previous participation in another interventional burn wound study within 60 days prior to the Screening Visit.
• Subject report of concurrent participation in another clinical trial that involves an investigational drug or device that would interfere with this study.
• The subject has any physical or psychiatric condition that in the Investigator's opinion would warrant exclusion from the study or prevent the subject from completing the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tacrolimus Ointment 0.03% with hydrocolloid dressing; Standard out-patient wound cleaning followed by application of tacrolimus ointment over the burn and hydrocolloid dressing on the treated area.	Drug: Tacrolimus ointment; For the active comparator group, the wound(s) will be cleaned and bacitracin ointment will be applied to the wound. External dressings on all treated wounds will be placed based on the current standard of care. For the control group, the wound(s) will be cleaned and a hydrocolloid Dressing will be affixed to the burn and treated area. For the treatment group, the wound(s) will be cleaned and tacrolimus (0.03%) ointment will be applied over the burn. Hydrocolloid Dressing will be affixed to the burn and treated area. External dressings on all treated wounds will be placed based on the current standard of care.; Other Names: Protopic® ointment
No Intervention: Bacitracin ointment; Standard out-patient wound cleaning followed by application of bacitracin ointment over the burn and hydrocolloid dressing on the treated area.
No Intervention: Hydrocolloid dressing; Standard out-patient wound cleaning followed by application of hydrocolloid dressing on the burned area.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to complete wound healing	Clinical burn wound assessment	21 days

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Wesley Thayer, MD, PhD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: May 3, 2023
• First Submitted That Met QC Criteria: May 3, 2023
• First Posted (Actual): May 12, 2023

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Burns; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 222242

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No