Topical Clobetasol for the Treatment of Toxic Epidermal Necrolysis (TEN)

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)

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).

Study Overview

• Status: Withdrawn
• Conditions: Toxic Epidermal Necrolysis
• Intervention / Treatment: Drug: Clobetasol 0.05% ointment; Drug: Placebo

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 Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95816
      • University of California, Davis Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 85 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Clobetasol 0.05% ointment; 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.	Drug: Clobetasol 0.05% ointment; Blinded, daily application to one arm for a period of fourteen (14) days
PLACEBO_COMPARATOR: Placebo; All patients will have one arm assigned to receive the placebo treatment (topical petrolatum ointment) applied daily for a period of fourteen days.	Drug: Placebo; Blinded, daily application to one arm for a period of fourteen (14) days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (numeric cellulitis score)	Local infection (cellulitis) is a potential complication of treatment with topical steroid ointment. A primary outcome measure of the study will be to determine if any difference in local infection rate exists between between control and clobetasol-treated skin in patients with toxic epidermal necrolysis, determined by daily assessments and assignment of a numeric cellulitis score.	14 days
Time to Cessation of Skin Detachment	The time until cessation of skin detachment (measured in days) will be determined though daily skin examinations and compared between the clobetasol and placebo-treated skin of patients with toxic epidermal necrolysis.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to 90% re-epithelialization	The time to 90% re-epithelialization will be determined by daily skin examinations and recorded in days to determine if a significant difference exists between control and clobetasol treated skin.	14 days
Percent Affected Surface Area	Percent affected surface area will be measured with daily skin examinations and compared between the placebo and steroid treated skin in patients with TEN	14 days
Percent Affected Surface Area Detached Skin	The percent body surface area affected by detached skin will be monitored through daily skin examinations and compared between the clobetasol and placebo treated skin in patients with toxic epidermal necrolysis.	14 days

Collaborators and Investigators

• Sponsor: University of California, Davis

Publications and helpful links

General Publications

• Wilken R, Li CS, Sharon VR, Kim K, Patel FB, Patel F, Maverakis E. Topical clobetasol for the treatment of toxic epidermal necrolysis: study protocol for a randomized controlled trial. Trials. 2015 Aug 22;16:374. doi: 10.1186/s13063-015-0879-7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ACTUAL): February 6, 2019
• Study Completion (ACTUAL): February 6, 2019

Study Registration Dates

• First Submitted: December 15, 2014
• First Submitted That Met QC Criteria: December 17, 2014
• First Posted (ESTIMATE): December 18, 2014

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2019
• Last Update Submitted That Met QC Criteria: August 7, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Skin Diseases; Immune System Diseases; Stomatognathic Diseases; Mouth Diseases; Hypersensitivity; Erythema; Skin Diseases, Vesiculobullous; Dermatitis; Drug-Related Side Effects and Adverse Reactions; Stomatitis; Drug Eruptions; Erythema Multiforme; Drug Hypersensitivity; Stevens-Johnson Syndrome; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Clobetasol
• Other Study ID Numbers: 804284

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No