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

NCT01276314 | Completed Results DMC

• 1 other identifier: 97-1413A3
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug Hypersensitivity

Keywords

SCAR; anti-TNF-a

Outcome Measures

Primary Outcomes (1)

• Skin Healing Time

  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.

Study Arms (2)

anti- TNF-a treatment

EXPERIMENTAL

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

control group

ACTIVE COMPARATOR

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

Interventions

anti- TNF-a DRUG

25mg BIW, SC

Also known as: Etanercept

anti- TNF-a treatment

Prednisolone DRUG

1-1.5 mg / kg / day

Also known as: steroid therapy

control group

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female patient aged more than 4 years.
• Inform consent obtained.

You may not qualify if:

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

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead
• National Science and Technology Council, Taiwan: collaborator

Study Sites (1)

Department of Dermatology, Chang Gung Memorial hospital

Taipei, 105, Taiwan

Location

Related Publications (4)

• Paquet P, Paquet F, Al Saleh W, Reper P, Vanderkelen A, Pierard GE. Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis. Am J Dermatopathol. 2000 Oct;22(5):413-7. doi: 10.1097/00000372-200010000-00005.

  PMID: 11048976 BACKGROUND

• Schneck J, Fagot JP, Sekula P, Sassolas B, Roujeau JC, Mockenhaupt M. Effects of treatments on the mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective study on patients included in the prospective EuroSCAR Study. J Am Acad Dermatol. 2008 Jan;58(1):33-40. doi: 10.1016/j.jaad.2007.08.039. Epub 2007 Oct 4.

  PMID: 17919775 RESULT

• Paradisi A, Abeni D, Bergamo F, Ricci F, Didona D, Didona B. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014 Aug;71(2):278-83. doi: 10.1016/j.jaad.2014.04.044. Epub 2014 Jun 11.

  PMID: 24928706 RESULT

• Wang CW, Yang LY, Chen CB, Ho HC, Hung SI, Yang CH, Chang CJ, Su SC, Hui RC, Chin SW, Huang LF, Lin YY, Chang WY, Fan WL, Yang CY, Ho JC, Chang YC, Lu CW, Chung WH; the Taiwan Severe Cutaneous Adverse Reaction (TSCAR) Consortium. Randomized, controlled trial of TNF-alpha antagonist in CTL-mediated severe cutaneous adverse reactions. J Clin Invest. 2018 Mar 1;128(3):985-996. doi: 10.1172/JCI93349. Epub 2018 Feb 5.

  PMID: 29400697 DERIVED

MeSH Terms

Conditions

Drug Hypersensitivity; Cicatrix

Interventions

Etanercept; Prednisolone

Condition Hierarchy (Ancestors)

Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Drug Hypersensitivity Clinical and Research Center, Laboratory of Dr. Wen-Hung Chung,
• Organization: Chang Gung Memorial Hospital, Linko

kiruamairo@gmail.com

886-3-328-1200

Study Officials

• Wen-Hung Chung, MD

  Department of Dermatology, CGMH

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2009
• First Posted: January 13, 2011
• Study Start: January 1, 2009
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: December 19, 2017
• Results First Posted: December 19, 2017

Record last verified: 2014-12

Locations

TW (1)