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

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ClinicalTrials.gov Identifier: NCT01276314
Recruitment Status : Completed
First Posted : January 13, 2011
Results First Posted : December 19, 2017
Last Update Posted : December 19, 2017
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by (Responsible Party):
Chang Gung Memorial Hospital

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.

Condition or disease Intervention/treatment Phase
Drug Hypersensitivity Drug: anti- TNF-a Drug: Prednisolone Not Applicable

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  (Clinical Trial)
Actual Enrollment : 135 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of TNF-α Blockade Effect in Patients With Severe Cutaneous Adverse Drug Reactions (SCAR)
Study Start Date : January 2009
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine


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 Name: 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 Name: steroid therapy




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01276314


Locations
Taiwan
Department of Dermatology, Chang Gung Memorial hospital
Taipei, Taiwan, 105
Sponsors and Collaborators
Chang Gung Memorial Hospital
National Science Council, Taiwan
Investigators
Study Chair: Wen-Hung Chung, MD Department of Dermatology, CGMH

Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT01276314     History of Changes
Other Study ID Numbers: 97-1413A3
First Posted: January 13, 2011    Key Record Dates
Results First Posted: December 19, 2017
Last Update Posted: December 19, 2017
Last Verified: December 2014

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Chang Gung Memorial Hospital:
SCAR
anti-TNF-a

Additional relevant MeSH terms:
Hypersensitivity
Drug-Related Side Effects and Adverse Reactions
Drug Hypersensitivity
Immune System Diseases
Chemically-Induced Disorders
Prednisolone acetate
Methylprednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Etanercept
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents