Ignite Creation Date:
2025-12-24 @ 6:59 PM
Ignite Modification Date:
2025-12-25 @ 4:32 PM
Study NCT ID:
NCT02987257
Status:
COMPLETED
Last Update Posted:
2025-12-17
First Post:
2016-11-25
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
NATIENS: Optimal Management and Mechanisms of SJS/TEN
Sponsor:
Vanderbilt University Medical Center
Organization:
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NATIENS
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.
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.
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: