Clinical Trial: Cyclosporine and Etanercept in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Phase III Randomized Trial of the Treatment of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Comparing Supportive Care, Cyclosporine, and Biologic Therapy in Adults

Brief Summary: 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.

Detailed Summary:

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 com
Sponsor: Ottawa Hospital Research Institute

Current Primary Outcome: Time to complete re-epithelialization [ Time Frame: 3 weeks ]

Absence of erosion and compromised skin


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Time to first sign of healing or halting of disease progression [ Time Frame: 2 weeks ]
    No new lesions, cessation of denudation of skin, or any sign of reversal of sloughing
  • All-cause mortality [ Time Frame: 3 weeks ]
    Death from any cause while admitted to the hospital
  • Composite disease-specific mortality [ Time Frame: 3 weeks ]
    Death from sepsis, multi-organ failure, or acute respiratory distress syndrome related to SJS/TEN
  • Predicted mortality (SCORTEN) versus actual mortality [ Time Frame: 3 weeks ]
    SCORTEN-predicted mortality for a given patient versus individual patient
  • Adverse events secondary to treatment [ Time Frame: 2 weeks ]
    Side effects related to treatment with cyclosporine or etanercept
  • Hospital length of stay [ Time Frame: 4 weeks ]
  • Mortality at 3 months after disease onset [ Time Frame: 3 months ]
    Analysis of the previously described increase in mortality within 3 months of disease onset and changes with therapy
  • Chronic mucocutaneous morbidity [ Time Frame: 3 months ]
    Complications related to SJS/TEN as measured at the 3 month follow-up. This includes ongoing skin changes or systemic consequences.
  • Nosocomial Infection [ Time Frame: 2-3 weeks ]
    Infection rate during the course of treatment


Original Secondary Outcome:

  • Time to first sign of healing or halting of disease progression [ Time Frame: 2 weeks ]
    No new lesions, cessation of denudation of skin, or any sign of reversal of sloughing
  • All-cause mortality [ Time Frame: 3 weeks ]
    Death from any cause while admitted to the hospital
  • Composite disease-specific mortality [ Time Frame: 3 weeks ]
    Death from sepsis, multi-organ failure, or acute respiratory distress syndrome related to SJS/TEN
  • Predicted mortality (SCORTEN) versus actual mortality [ Time Frame: 3 weeks ]
    SCORTEN-predicted mortality for a given patient versus individual patient
  • Adverse events secondary to treatment [ Time Frame: 2 weeks ]
    Side effects related to treatment with cyclosporine or etanercept
  • Hospital length of stay [ Time Frame: 4 weeks ]
  • Mortality at 3 months after disease onset [ Time Frame: 3 months ]
    Analysis of the previously described increase in mortality within 3 months of disease onset and changes with therapy
  • Chronic mucocutaneous morbidity [ Time Frame: 3 months ]
    Complications related to SJS/TEN as measured at the 3 month follow-up. This includes ongoing skin changes or systemic consequences.


Information By: Ottawa Hospital Research Institute

Dates:
Date Received: November 25, 2016
Date Started: August 2018
Date Completion: August 2022
Last Updated: March 28, 2017
Last Verified: March 2017