Topical clobetasol for the treatment of toxic epidermal necrolysis: Study protocol for a randomized controlled trial

Reason Wilken, Chin-Shang Li, Victoria R. Sharon, Kyoungmi Kim, Falin B. Patel, Forum Patel, Emanual Michael Maverakis

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Toxic epidermal necrolysis (TEN) is a rare systemic allergic drug eruption with high patient mortality. Currently, no established treatments have been shown to be effective for TEN beyond supportive care. Prior studies of systemic corticosteroids have yielded conflicting data, with some showing a possible benefit and others reporting in increased mortality. However, topical steroids have shown promise for treatment of ocular sequelae of TEN, such as scarring and vision loss. We have designed a randomized controlled trial to evaluate topical clobetasol for treatment of the epidermal manifestations of TEN. In addition, we propose genetic studies to characterize the TEN transcriptome and alterations in cutaneous gene expression that might occur following topical steroid treatment. Methods/Design: This split-body randomized, double-blind, placebo-controlled Phase IIa proof-of-concept trial will evaluate the safety and efficacy of once-daily topical clobetasol applied to the skin of patients with TEN. This multicenter trial will recruit a total of 15 patients between the ages of 12 and 85 from the University of California Davis Medical Center and Shriners Hospital for Children inpatient burn units. Designated treatment areas on opposite sides of the body will be treated with blinded clobetasol 0.05 % ointment or control petrolatum ointment daily for 14 days. On day 3 of therapy, a biopsy will be taken from the treated area for genetic studies. The primary study aims will be to establish the safety of topical clobetasol treatment and determine the time to cessation of skin detachment for the control and clobetasol-treated areas. Secondary endpoints will evaluate efficacy using parameters such as time to 90 % re-epithelialization and percentage of affected skin at 0, 3, 6, 9, 12 and 15 days. Genomic DNA and RNA will be obtained from biopsy samples, to characterize the TEN transcriptome and identify changes in gene expression after topical steroid treatment. Discussion: Topical steroids have shown promise for treating ocular complications of TEN, but to date have not been evaluated for cutaneous manifestations of the disease. This trial will investigate clinical and molecular outcomes of topical clobetasol application and hopefully provide insight into the disease pathophysiology. Trial registration: ClinicalTrials.gov NCT02319616. https://clinicaltrials.gov/ct2/show/NCT02351037.

Original languageEnglish (US)
Article number374
JournalTrials
Volume16
Issue number1
DOIs
StatePublished - Aug 22 2015

Fingerprint

Clobetasol
Stevens-Johnson Syndrome
Randomized Controlled Trials
Steroids
Skin
Therapeutics
Ointments
Transcriptome
Re-Epithelialization
Petrolatum
Drug Eruptions
Biopsy
Skin Manifestations
Safety
Gene Expression
Burn Units
Mortality
Skin Diseases
Multicenter Studies
Cicatrix

Keywords

  • Apoptosis
  • Clobetasol
  • Stevens-Johnson syndrome
  • Topical steroids
  • Toxic epidermal necrolysis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)

Cite this

Topical clobetasol for the treatment of toxic epidermal necrolysis : Study protocol for a randomized controlled trial. / Wilken, Reason; Li, Chin-Shang; Sharon, Victoria R.; Kim, Kyoungmi; Patel, Falin B.; Patel, Forum; Maverakis, Emanual Michael.

In: Trials, Vol. 16, No. 1, 374, 22.08.2015.

Research output: Contribution to journalArticle

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abstract = "Background: Toxic epidermal necrolysis (TEN) is a rare systemic allergic drug eruption with high patient mortality. Currently, no established treatments have been shown to be effective for TEN beyond supportive care. Prior studies of systemic corticosteroids have yielded conflicting data, with some showing a possible benefit and others reporting in increased mortality. However, topical steroids have shown promise for treatment of ocular sequelae of TEN, such as scarring and vision loss. We have designed a randomized controlled trial to evaluate topical clobetasol for treatment of the epidermal manifestations of TEN. In addition, we propose genetic studies to characterize the TEN transcriptome and alterations in cutaneous gene expression that might occur following topical steroid treatment. Methods/Design: This split-body randomized, double-blind, placebo-controlled Phase IIa proof-of-concept trial will evaluate the safety and efficacy of once-daily topical clobetasol applied to the skin of patients with TEN. This multicenter trial will recruit a total of 15 patients between the ages of 12 and 85 from the University of California Davis Medical Center and Shriners Hospital for Children inpatient burn units. Designated treatment areas on opposite sides of the body will be treated with blinded clobetasol 0.05 {\%} ointment or control petrolatum ointment daily for 14 days. On day 3 of therapy, a biopsy will be taken from the treated area for genetic studies. The primary study aims will be to establish the safety of topical clobetasol treatment and determine the time to cessation of skin detachment for the control and clobetasol-treated areas. Secondary endpoints will evaluate efficacy using parameters such as time to 90 {\%} re-epithelialization and percentage of affected skin at 0, 3, 6, 9, 12 and 15 days. Genomic DNA and RNA will be obtained from biopsy samples, to characterize the TEN transcriptome and identify changes in gene expression after topical steroid treatment. Discussion: Topical steroids have shown promise for treating ocular complications of TEN, but to date have not been evaluated for cutaneous manifestations of the disease. This trial will investigate clinical and molecular outcomes of topical clobetasol application and hopefully provide insight into the disease pathophysiology. Trial registration: ClinicalTrials.gov NCT02319616. https://clinicaltrials.gov/ct2/show/NCT02351037.",
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AU - Kim, Kyoungmi

AU - Patel, Falin B.

AU - Patel, Forum

AU - Maverakis, Emanual Michael

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