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Defining the true effect of adjunctive therapy for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) on time to full healing, mortality, and long-term outcomes represents a critical need in the field of dermatology and burn surgery. Collaborating with 20 sites from across North America we will determine if cyclosporine or etanercept therapy improves SJS/TEN short outcomes above supportive care alone The scientific premise for this study is that case series, cohorts, and small non-randomized studies have not supported the use of non-pulsed corticosteroids and intravenous immunoglobulin (IVIG), while showing the promise of cyclosporine and etanercept in reducing the time to complete re-epithelialization. By indirect comparison, etanercept appears to be superior in small studies, however none of the studies have evaluated these therapies in a blinded and randomized trial. Additionally, we will uncover the underlying process of SJS/TEN through the analysis of skin samples, blood, blister fluid and immune cells to study the immune system and changes in gene expression with and without drug therapy. This will improve the treatment of patients in the future.
Aim 1: Establish the most effective therapy for SJS/TEN. A multi-centered, double-blind randomized control trial including 20 sites with an enrollment of 267 patients over 4 years will be undertaken to understand which of supportive care, cyclosporine or etanercept causes the greatest reduction in time to complete re-epithelialization. Assessment of the primary outcome will occur using a previously validated method consisting of two independent assessors and digital photograph analysis. Secondary outcomes will include all-cause mortality, time to cessation of disease progression, adverse effects related to a study medication, secondary chronic mucocutaneous morbidity, and hospital length of stay. Subgroup analysis will be performed to examine differences for treatment between gender, SCORTEN, percent body surface area (%BSA) and drug half-life.
Aim 2: Enhance our understanding of genetic and biomarker predictors in SJS/TEN. Genome sequencing and transcriptome profiling will be used to evaluate changes in expression over time within each treatment arm to identify involved genes and responses to treatment. Changes over the course of hospitalization and at the follow-up visit will be tested. Additionally, high resolution HLA and Mega chip typing will be performed on individuals with a clear drug cause according to the Algorithm of Drug Causality for Epidermal Necrolysis (ALDEN) Score. These will be matched to drug tolerant controls. Third, measurement of granulysin will occur at presentation and serial time points to establish its role as a predictive biomarker in disease prognosis and response to treatment.
Aim 3: To gain insights into the immunopathogenesis of SJS/TEN. We will collect blister fluid, skin biopsies and peripheral blood mononuclear cells (PBMCs) during the acute SJS/TEN reaction before treatment, following completion of treatment (PBMCs), and on follow-up from recovery PBMCs. This will analyze T-cell changes and gene expression as it relates to the disease and treatment. We expect that this will direct therapy for the future.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
cyclosporin A, Etanercept 50 MG Solution for Injection, Placebos
Not yet recruiting
Ottawa Hospital Research Institute
Published on BioPortfolio: 2016-12-08T17:38:23-0500
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Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol.
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Interruption of the conduction of impulses in peripheral nerves or nerve trunks by the injection of a local anesthetic solution. (Stedman, 26th ed)
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