Stevens-Johnson SyndromePhase 3NATIENSNCT02987257
NATIENS: Optimal Management and Mechanisms of SJS/TEN
A Phase 3 study testing Harmonized supportive care and Etanercept 50 mg sc day 1 and day 4 in people with Stevens-Johnson Syndrome and Toxic Epidermal Necrolyses, run by Vanderbilt University Medical Center at 14 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stevens-Johnson Syndrome, Toxic Epidermal Necrolyses
- What is being tested?
- Harmonized supportive care and Etanercept 50 mg sc day 1 and day 4
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 14 sitesUnited States
- Study dates
- 21 Mar 2023to 31 Oct 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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).
Show all 20Show fewer
- 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.
- Known positive SARS-CoV-2 on RT-PCR within 10 days prior to screening or within 5 days of admission or symptomatic COVID-19 infection at screening. Symptomatic patients with a positive SARS-CoV-2 on RT-PCR or comparable assay beyond 10 days must be evaluated by the Independent Protocol Monitor.
- Clinical or radiographic evidence of active tuberculosis or endemic mycoses.
- History or evidence of any other clinically significant medical or psychiatric disorder, condition or disease that in the opinion of the treating physician would pose a risk or interfere with evaluation or completion of the study such as known sepsis/systemic infection requiring antibiotic therapy.
- Known hypersensitivity to Enbrel® (etanercept).
- Receipt of a live attenuated vaccine within 30 days of enrollment.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Emory University at Grady Memorial Hospital
Atlanta, Georgia, 30303
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Wayne State University
Detroit, Michigan, 48201
University of Florida Health Burn Center
Gainesville, Florida, 32610
University of Texas Medical Branch
Galveston, Texas, 77555
Loyola University Medical Center
Maywood, Illinois, 60153
University of Tennessee Health Sciences Center
Memphis, Tennessee, 38103
University of Miami, Ryder Trauma Center
Miami, Florida, 33136
Vanderblt University Medical Center
Nashville, Tennessee, 37232
Valleywise Health Medical Center
Phoenix, Arizona, 85008
University of California, Davis Medical Center
Sacramento, California, 95817
University of Washington, Harborview Medical Center
Seattle, Washington, 98104
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
About this study
Official title: NATIENS: A Phase III Randomized Double-Blinded Placebo Controlled Study to Determine the Optimal Management and Mechanisms of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
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.
Read the detailed description
The scientific rationale for this study is the lack of evidence-based treatment for SJS/TEN. The study will aim to establish the most clinically effective therapy for SJS/TEN, as there is currently no level 1A evidence for any treatment above aggressive supportive care which still has equipoise as the standard of care. A multi-centered, two-arm allocated 1:1, double-blind randomized controlled trial with a planned enrollment of 150 patients over 4 years will be undertaken to evaluate which of supportive care or etanercept leads to the shortest time to complete reepithelialization which is the primary outcome. The controlled setting of the clinical trial provides the basis for which samples can be sequentially collected to answer important mechanistic questions. Samples collected during the study will include DNA, PBMC, RNA, plasma, serum, blister fluid cells and supernatant, sloughed epidermis and punch biopsies of skin. Samples will be bio-banked to do immediate targeted high-resolution HLA sequencing, cytokine profiling and single cell multidimensional analyses to identify biological markers that have the potential to predict risk and outcome of SJS/TEN. A population pharmacokinetic study to assess the disposition of etanercept will be done by collecting five samples over the course of the study. Samples will be biobanked for later analysis for other transcriptomic, proteomic whole genome studies. These mechanistic studies will allow us to gain important insights into the immunopathogenesis of SJS/TEN. Our study will be the first to examine in a blinded randomized controlled design both management and mechanisms of SJS/TEN. We anticipate that this will lead to new ways to prevent, diagnosis and treat SJS/TEN, and will create a roadmap and evidence-base for studies in serious immunologically mediated adverse drug reactions and other immunologically mediated diseases.
This protocol represents the only appropriately powered randomized, double-blind mechanistic clinical trial examining therapeutic interventions for SJS/TEN. It will address several significant gaps in knowledge. From a management perspective, it will provide the highest level of supportive care and prove or refute the benefits of etanercept that is a promising therapy for SJS/TEN. The NATIENS trial will also define the standard for systematically assessing the benefit of a systemic intervention for SJS/TEN in prospective studies. We also hope to identify key biomarkers as well as immunologic and genetic determinants for risk, rapid diagnosis, baseline pathophysiology, and mechanisms of response to therapy. The population pharmacokinetics of etanercept will be established for the first time in this critically ill population to improve future dosing strategies and make recommendations. Finally, the protocols and procedures related to patient care will establish a standard for harmonization of care for these patients to provide the best outcomes possible. The study is likely to result in paradigm shifting knowledge regarding SJS/TEN treatment, diagnosis, prevention, and pathogenesis that will lead to improved care for future SJS/TEN patients.
- Being tested
- Harmonized supportive care, Etanercept 50 mg sc day 1 and day 4
- Keywords
- Therapeutics, Management, Etanercept, Supportive Care, Immunopathogenesis, Genetics, Adverse Drug Reaction
- Medical subject headings
- Stevens-Johnson Syndrome, Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Harmonized supportive careDrug
Harmonized supportive care with and etanercept placebo days 1 and 4
Etanercept 50 mg sc day 1 and day 4Drug
Harmonized supportive care with placebo
| Study group | Role | What they receive |
|---|---|---|
| Harmonized supportive care | Placebo comparator | Harmonized supportive care with etanercept placebo days 1 and 4 Receives: Drug: Harmonized supportive care |
| Etanercept 50mg sc day 1 and day 4 | Active comparator | Harmonized supportive care with placebo days 1 and 4 Receives: Drug: Harmonized supportive care; Drug: Etanercept 50 mg sc day 1 and day 4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: up to 4 weeks
Secondary outcomes (7)
Time to halting of progression of SJS/TEN skin disease
Progression will be considered significant if there are any new blistering lesions or any new detached or detachable skin.
Measured: up to 4 weeks
Mortality
Number of participants with mortality at 30 days, 3 months and 1 year
Measured: up to 1 year
Mortality
Number of participants with Actual mortality versus expected mortality for each SCORTEN risk
Measured: up to 4 weeks
Ocular involvement
Time to cessation of acute ocular involvement acutely then extent of ocular involvement at follow-up will be assessed by two independent ophthalmology experts. Will be tracked by photography
Measured: up to 1 year or study outcome
Infections
Incidence of nosocomial infections
Measured: up to 4 weeks
Hospital length of stay
Duration of time in hospital
Measured: up to 4 weeks
Proportion of patients with Adverse events due to assigned treatment arm
Adverse events due to assigned treatment arm
Measured: up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2016 (estimated)
- Study start21 Mar 2023
- Primary completion31 Oct 2025
- Study completion31 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stevens-Johnson SyndromeStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ottawa, University of Toronto
- Responsible party
- Principal investigator, Elizabeth J Phillips, Vanderbilt University Medical Center
- Investigators
- Elizabeth J Phillips, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02987257
- Sponsor's protocol ID
- 212370
- Acronym
- NATIENS
- Status last verified
- Dec 2025
- First submitted
- 25 Nov 2016
- Last updated
- 17 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There are no plans to share individual participant data available to other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NATIENS: A Phase III Randomized Double-Blinded Placebo Controlled Study to Determine the Optimal Management and Mechanisms of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
- ClinicalTrials.gov ID
- NCT02987257
- Acronym / sponsor ID
- NATIENS / 212370
- Keywords
- Therapeutics, Management, Etanercept, Supportive Care, Immunopathogenesis, Genetics, Adverse Drug Reaction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- University of Ottawa, University of Toronto
- Study start
- 21 Mar 2023 (actual)
- Primary completion
- 31 Oct 2025 (actual)
- Study completion
- 31 Oct 2025 (actual)
- First posted
- 8 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The scientific rationale for this study is the lack of evidence-based treatment for SJS/TEN. The study will aim to establish the most clinically effective therapy for SJS/TEN, as there is currently no level 1A evidence for any treatment above aggressive supportive care which still has equipoise as the standard of care. A multi-centered, two-arm allocated 1:1, double-blind randomized controlled trial with a planned enrollment of 150 patients over 4 years will be undertaken to evaluate which of supportive care or etanercept leads to the shortest time to complete reepithelialization which is the primary outcome. The controlled setting of the clinical trial provides the basis for which samples can be sequentially collected to answer important mechanistic questions. Samples collected during the study will include DNA, PBMC, RNA, plasma, serum, blister fluid cells and supernatant, sloughed epidermis and punch biopsies of skin. Samples will be bio-banked to do immediate targeted high-resolution HLA sequencing, cytokine profiling and single cell multidimensional analyses to identify biological markers that have the potential to predict risk and outcome of SJS/TEN. A population pharmacokinetic study to assess the disposition of etanercept will be done by collecting five samples over the course of the study. Samples will be biobanked for later analysis for other transcriptomic, proteomic whole genome studies. These mechanistic studies will allow us to gain important insights into the immunopathogenesis of SJS/TEN. Our study will be the first to examine in a blinded randomized controlled design both management and mechanisms of SJS/TEN. We anticipate that this will lead to new ways to prevent, diagnosis and treat SJS/TEN, and will create a roadmap and evidence-base for studies in serious immunologically mediated adverse drug reactions and other immunologically mediated diseases.
This protocol represents the only appropriately powered randomized, double-blind mechanistic clinical trial examining therapeutic interventions for SJS/TEN. It will address several significant gaps in knowledge. From a management perspective, it will provide the highest level of supportive care and prove or refute the benefits of etanercept that is a promising therapy for SJS/TEN. The NATIENS trial will also define the standard for systematically assessing the benefit of a systemic intervention for SJS/TEN in prospective studies. We also hope to identify key biomarkers as well as immunologic and genetic determinants for risk, rapid diagnosis, baseline pathophysiology, and mechanisms of response to therapy. The population pharmacokinetics of etanercept will be established for the first time in this critically ill population to improve future dosing strategies and make recommendations. Finally, the protocols and procedures related to patient care will establish a standard for harmonization of care for these patients to provide the best outcomes possible. The study is likely to result in paradigm shifting knowledge regarding SJS/TEN treatment, diagnosis, prevention, and pathogenesis that will lead to improved care for future SJS/TEN patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Harmonized supportive care | Placebo comparator | Drug: Harmonized supportive careHarmonized supportive care with etanercept placebo days 1 and 4 |
| Etanercept 50mg sc day 1 and day 4 | Active comparator | Drug: Harmonized supportive care, Drug: Etanercept 50 mg sc day 1 and day 4Harmonized supportive care with placebo days 1 and 4 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- History of a newly used medication within the last 2 months that has not been tolerated for longer than 12 weeks in the past
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Harmonized supportive careHarmonized supportive care with and etanercept placebo days 1 and 4 | Drug | Etanercept 50mg sc day 1 and day 4, Harmonized supportive care |
| Etanercept 50 mg sc day 1 and day 4Harmonized supportive care with placebo | Drug | Etanercept 50mg sc day 1 and day 4 |
Primary outcome
Time to complete re-epithelialization
Time frame: up to 4 weeks
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)
7 secondary outcomes
Time to halting of progression of SJS/TEN skin disease
Time frame: up to 4 weeks
Mortality
Time frame: up to 1 year
Mortality
Time frame: up to 4 weeks
Ocular involvement
Time frame: up to 1 year or study outcome
Infections
Time frame: up to 4 weeks
Hospital length of stay
Time frame: up to 4 weeks
Proportion of patients with Adverse events due to assigned treatment arm
Time frame: up to 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
- Individual participant dataSharing planned: No. There are no plans to share individual participant data available to other researchers.
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New Therapeutic Target for Toxic Epidermal Necrolysis (TEN) Using Anti-CD38+ Monoclonal Antibodies.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth J Phillips, MD principal investigator
Vanderbilt University Medical Center
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Harmonized supportive care and Etanercept 50 mg sc day 1 and day 4 in people with Stevens-Johnson Syndrome and Toxic Epidermal Necrolyses, run by Vanderbilt University Medical Center at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to complete re-epithelialization (time frame: up to 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.