NATIENS: Optimal Management and Mechanisms of SJS/TEN

NCT02987257 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 212370
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 14

Brief Summary

The North American Therapeutics in Epidermal Necrolysis Syndrome (NATIENS) study is a multicenter double-blind randomized controlled assessment of two arms - one of systemic immunomodulatory therapy (etanercept) and one of supportive care deemed to be the current standard of care. We will leverage the opportunity of this controlled design to collect multiples samples with an aim to discover new genetic and biological markers for prevention and early diagnosis and define cellular and molecular mechanisms to facilitate discovery of promising treatment strategies. This study has been preceded by a planning phase to ensure testing and development of harmonized supportive care infrastructure and operating procedures across sites.

Conditions

Stevens-Johnson Syndrome; Toxic Epidermal Necrolyses

Keywords

Therapeutics; Management; Etanercept; Supportive Care; Immunopathogenesis; Genetics; Adverse Drug Reaction

Outcome Measures

Primary Outcomes (1)

• Time to complete re-epithelialization

  Patients will be assessed by two independent raters (burn surgeons, dermatologists, wound care experts) to determine the day of full re-epithelialization. For disagreements on the day of re-epithelialization the case with supporting photographs will be referred to an independent adjudication committee comprised of a minimum of three experts (a burn surgeon, dermatologist, wound care expert). In the instance of death will be the maximum period of re-epithelialization (21 days + 1)

  up to 4 weeks

Secondary Outcomes (7)

• Time to halting of progression of SJS/TEN skin disease

  up to 4 weeks

• Mortality

  up to 1 year

• Mortality

  up to 4 weeks

• Ocular involvement

  up to 1 year or study outcome

• Infections

  up to 4 weeks

Other Outcomes (1)

• Granulysin, IL-15 and other cytokine measurements

  up to 1 year or study outcome

Study Arms (2)

Harmonized supportive care

PLACEBO COMPARATOR

Harmonized supportive care with etanercept placebo days 1 and 4

Drug: Harmonized supportive care

Etanercept 50mg sc day 1 and day 4

ACTIVE COMPARATOR

Harmonized supportive care with placebo days 1 and 4

Drug: Harmonized supportive care; Drug: Etanercept 50 mg sc day 1 and day 4

Interventions

Harmonized supportive care DRUG

Harmonized supportive care with and etanercept placebo days 1 and 4

Etanercept 50mg sc day 1 and day 4; Harmonized supportive care

Etanercept 50 mg sc day 1 and day 4 DRUG

Harmonized supportive care with placebo

Etanercept 50mg sc day 1 and day 4

Eligibility Criteria

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

You may qualify if:

• Age \>18 years
• Subject and/or legally authorized representative must be able to understand and provide informed consent.
• Erythematous to dusky macules that show evidence of coalescing and/or denuding skin or blistering in a predominantly truncal distribution (Nikolsky sign = sloughing with direct lateral pressure on non-blistered but involved skin should be considered as a supportive feature
• At least two of the following:
• Mucous membrane involvement
• Prodromal symptoms including fever, myalgia, and headache
• Evidence of disease progression with an increasing number of skin lesions
• History of a newly used medication within the last 2 months that has not been tolerated for longer than 12 weeks in the past
• Females of childbearing potential must have a negative pregnancy test prior to randomization.

You may not qualify if:

• Subject or legally authorized representative is not willing to provide informed consent.
• A serious drug reaction or possible alternative dermatologic diagnosis at the time of initial evaluation not in keeping with drug-induced SJS/TEN (e.g. graft versus host disease).
• If greater than 5 days has elapsed from onset of initial cutaneous or mucosal signs of the disease as obtained by patient history or documentation.
• Patients who have received etanercept in the last 6 months.
• Patients who in time since onset of SJS/TEN illness have received intravenous immune globulin (IVIg) or \> 2 doses of pulsed corticosteroid (defined by \> 250 mg prednisone equivalent) prior to enrollment in the study.
• End-stage liver disease (Child Pugh A, B or C or severe liver dysfunction).
• Grade 2 or higher liver dysfunction (alanine aminotransferase \>3 fold or bilirubin \>3 fold the upper limit of normal).
• Any organ transplant.
• Pre-existing Class III/IV Heart Failure (New York Heart Association Functional Classification).
• Multiple Sclerosis or other demyelinating diseases.
• Pregnancy or breastfeeding.
• Current or past history of immune checkpoint inhibitor therapy for cancer.
• Absolute need for a drug that interacts with cyclosporine without an appropriate substitution.
• History of other immunosuppressive or immunomodulatory therapy that could significant impact treatment or interpretation of response to treatment (i.e. azathioprine, methotrexate, mycophenolate mofetil, mycophenolate sodium, rituximab, JAK inhibitors, IL-17 inhibitors, IL-23 inhibitors, other TNF alpha antagonists (see MOP).
• Use of surgical debridement and/or xenograft.

Sponsors & Collaborators

• University of Toronto: collaborator
• Vanderbilt University Medical Center: lead
• University of Ottawa: collaborator

Study Sites (14)

Valleywise Health Medical Center

Phoenix, Arizona, 85008, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida Health Burn Center

Gainesville, Florida, 32610, United States

Location

University of Miami, Ryder Trauma Center

Miami, Florida, 33136, United States

Location

Emory University at Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of Tennessee Health Sciences Center

Memphis, Tennessee, 38103, United States

Location

Vanderblt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

University of Washington, Harborview Medical Center

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Stevens-Johnson Syndrome; Drug-Related Side Effects and Adverse Reactions

Interventions

Etanercept

Condition Hierarchy (Ancestors)

Stomatitis; Mouth Diseases; Stomatognathic Diseases; Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Erythema Multiforme; Erythema; Skin Diseases, Vesiculobullous; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Drug Hypersensitivity; Chemically-Induced Disorders

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

Study Officials

• Elizabeth J Phillips, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 25, 2016
• First Posted: December 8, 2016
• Study Start: March 21, 2023
• Primary Completion: October 31, 2025
• Study Completion: October 31, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)