Evaluation of TNF-α Blockade Effect in Patients With Severe Cutaneous Adverse Drug Reactions

December 17, 2017 updated by: Chang Gung Memorial Hospital

Evaluation of TNF-α Blockade Effect in Patients With Severe Cutaneous Adverse Drug Reactions (SCAR)

Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest mortality (30-35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but with less extensive skin detachment and a lower mortality (5-15%). Hypersensitivity syndrome, sometimes called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at about 10%. The aims of this project are (1) to compare the effect of treatment between systemic steroid and anti-TNF-α. Including skin healing time, beginning of re-epithelialization time, internal organ recovery time, mortality rate, adverse events and (2) to investigate the molecular mechanism of severe cutaneous adverse reaction after anti-TNF-α treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Severe cutaneous adverse drug reactions, including Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome(SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a life threatening disease. There is no gold standard in the therapy of SCAR. Treatment with high dose systemic corticosteroids is controversial. Although there have been recent reports of success with various therapies such as plasmapheresis and high-dose intravenous immunoglobulins, their efficacy is not yet proven. Assessment of these therapies is difficult because of their non-specific immunosuppressant or immunomodulating modes of action. Recent studies have shown evidence of the pathogenetic importance of tumour necrosis factor (TNF)-a, suggesting a new therapeutic approach in selective blockade of TNF-a using specific antibodies. We report successful treatment TEN using monoclonal IgG anti-TNF-antibodies. The aims of this project are (1) to compare the effect of treatment between systemic steroid and anti-TNF-α. Including skin healing time, beginning of re-epithelialization time, internal organ recovery time, mortality rate, adverse events and (2) to investigate the molecular mechanism of severe cutaneous adverse reaction after anti-TNF-α treatment.

Study Type

Interventional

Enrollment (Actual)

135

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan, 105
        • Department of Dermatology, Chang Gung Memorial hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female patient with clinical and pathological diagnoses of severe cutaneous adverse drug reactions such as Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis or Durg reaction with eosinophilia and systemic symptoms.
  2. Male or female patient aged more than 4 years.
  3. Inform consent obtained.

Exclusion Criteria:

  1. Pregnant or breastfeeding female.
  2. Allergic to any anti-TNF-α biological product.
  3. Active or latent tuberculosis confirmed with Chest X-ray.
  4. Severe active infection and septicemia.
  5. Active Hepatitis B or C carrier.
  6. Suspected HIV carrier with CD4 count less than 200.
  7. Patient with poor compliance or with safety concerns judged by investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: anti- TNF-a treatment
  1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
  2. Fill out the case report form
  3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
  4. Etanercept administration:

The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks
Drug: anti- TNF-a
25mg BIW, SC
Other Names:
  • Etanercept
Active Comparator: control group
  1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
  2. Fill out the case report form
  3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
  4. Drug administration:

The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose.
Drug: Prednisolone
1-1.5 mg / kg / day
Other Names:
  • steroid therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Skin Healing Time
Time Frame: One to two months for SJS/TEN cases, and one to six months for DRESS cases.
Healing was defined as complete re-epithelialization (i.e., the complete absence of erosions). We recorded the time taken by the skin to heal.
One to two months for SJS/TEN cases, and one to six months for DRESS cases.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chang Gung Memorial Hospital

Collaborators

National Science Council, Taiwan

Investigators

  • Study Chair: Wen-Hung Chung, MD, Department of Dermatology, CGMH

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

May 1, 2015

Study Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

July 5, 2009

First Submitted That Met QC Criteria

January 11, 2011

First Posted (Estimate)

January 13, 2011

Study Record Updates

Last Update Posted (Actual)

December 19, 2017

Last Update Submitted That Met QC Criteria

December 17, 2017

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 97-1413A3

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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