Topical Clobetasol for the Treatment of Toxic Epidermal Necrolysis

Brief Title

Topical Clobetasol for the Treatment of Toxic Epidermal Necrolysis

Official Title

A Randomized Placebo Controlled Split-body Double-blind Phase II Clinical Trial to Investigate the Safety and Efficacy of Clobetasol 0.05% Ointment for the Treatment of Toxic Epidermal Necrolysis (TEN)

Brief Summary

      The primary objectives of this study are to investigate the efficacy and safety of topical
      steroid ointment (clobetasol 0.05%) for the treatment of the cutaneous manifestations of
      toxic epidermal necrolysis (TEN).
    

Detailed Description

      The experimental focus of this trial is thus to evaluate the safety and clinical outcomes of
      topical steroid (clobetasol 0.05% ointment) for treatment of the cutaneous manifestations of
      toxic epidermal necrolysis (TEN).

      The design of the study is a randomized, placebo-controlled, double-blind split-body Phase II
      clinical trial in which clobetasol 0.05% or placebo ointment will be topically applied to
      opposite arms for a period of fourteen days. The primary endpoints of the study are to
      determine the time to cessation of skin detachment in both groups as well as the safety of
      topical clobetasol to treat the cutaneous manifestations of TEN. Secondary outcome measures
      will evaluate efficacy by comparing the time to re-epithelialization and the percentage of
      affected skin between the clobetasol and placebo arms at various time points.

      An additional aim of the study is to characterize the genes expressed during the TEN disease
      state and any changes in gene expression following treatment with topical steroids,
      particularly those genes involved in the regulation of programmed cell death (apoptosis).
      This will be accomplished though molecular analysis of skin biopsy specimens obtained after
      treatment with clobetasol and placebo ointments. The specific hypothesis being tested is that
      two weeks of topical clobetasol will promote epidermal keratinocyte survival through
      suppression of TNF signaling, decreased granulysin expression and inhibition of other
      pro-apoptotic pathways resulting in shorter disease duration and decreased time to
      re-epithelialization.

      IRB number: 642415-5
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Safety (numeric cellulitis score)

Secondary Outcome

 Time to 90% re-epithelialization

Condition

Toxic Epidermal Necrolysis

Intervention

Clobetasol 0.05% ointment

Study Arms / Comparison Groups

 Clobetasol 0.05% ointment

Description:  All patients will have one arm assigned to receive the experimental treatment (topical clobetasol 0.05% ointment) applied daily for a period of fourteen days.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

0

Start Date

November 2016

Completion Date

February 6, 2019

Primary Completion Date

February 6, 2019

Eligibility Criteria

        Inclusion Criteria:

          -  Characteristic histological findings on diagnostic biopsy

          -  Clinical diagnosis verified by two independent physicians

          -  Greater than 10% affected body surface area (BSA)

          -  Ability to start treatment within seven days or less from the onset of erosions

          -  Actively worsening disease (enlarging area of involvement or new erosions occurring
             over the last 24 hours)

          -  Patient Body Surface Area (BSA) > 1.0 m2

          -  Reproductive age female patients must have a negative pregnancy test prior to
             enrollment

        Exclusion Criteria:

          -  Patients will be excluded if they are < 7 or > 85 years of age.

          -  Patients who have documented:

               -  Uncontrolled infection (e.g. documented bacteremia)

               -  Malignancy

               -  Known prior immunodeficiency

               -  Pregnancy

               -  Concurrent use of systemic corticosteroids in the burn center greater than or
                  equal to 0.5 mg/kg/day of prednisone or equivalent dose of similar medication.

               -  Greater than 70% eroded skin

               -  SCORETEN score >3 on hospital admission

          -  Patients will also be excluded if they have: active hepatitis and/or an ALT or AST
             greater than four times the normal limits, or renal insufficiency with an estimated
             GFR<50 mL/min/1.73m2.
      

Gender

All

Ages

7 Years - 85 Years

Accepts Healthy Volunteers

No

Contacts

Emanual Maverakis, MD, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT02319616

Organization ID

804284

Responsible Party

Sponsor

Study Sponsor

University of California, Davis

Study Sponsor

Emanual Maverakis, MD, Principal Investigator, University of California, Davis

Verification Date

August 2019