Clinical trial NCT02319616: 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Toxic Epidermal Necrolysis
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2014-12-18
Enrollment: 0
Sex: ALL
Minimum age (years): 7
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Safety (numeric cellulitis score)
timeFrame: 14 days
measure: Time to Cessation of Skin Detachment
timeFrame: 14 days
Secondary outcomes:
measure: Time to 90% re-epithelialization
timeFrame: 14 days
measure: Percent Affected Surface Area
timeFrame: 14 days
measure: Percent Affected Surface Area Detached Skin
timeFrame: 14 days
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis Department of Dermatology
state: California
Study officials:
affiliation: University of California, Davis
name: Emanual Maverakis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.