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NCT04651439 | Not yet recruiting | Rare Diseases


Severe Bullous Drug Eruption and Filgrastim
Sponsor:

Hospices Civils de Lyon

Brief Summary:

Toxic epidermal necrolysis (TEN) including Stevens Johnson (SJS) and Lyell syndromes represent the most severe drug eruptions. It is an allergic disorder caused by cytotoxic T lymphocytes, specific of drugs, responsible for the destruction of keratinocytes by apoptosis. Regulatory T cell (CD25 high CD4+), normally responsible for controlling the activation of cytotoxic T lymphocytes, have altered function. Despite the progress made in the pathophysiological understanding of TEN, there is currently no effective treatment. The main symptom is bullous and skin peeling > 10% giving the appearance of great burns. The death rate is estimated between 30 and 40% due to visceral inflammatory injuries and bacterial superinfection. The risk of mortality is estimated during the initial treatment by calculating the SCORTEN (mortality>10% if SCORTEN>2, mortality>90% if SCORTEN>5). The morbidity is also very important (92% at 1 year), especially ophthalmologic with high risk of blindness... The therapeutic potential of G-CSF (Granulocyte-Colony Stimulating Factor) in TEN is supported by several observations. The G-CSF promotes skin healing. This has been shown in human burns, with a significant reduction in healing time under G-CSF. The mechanisms associate the growth factor effect on keratinocytes, macrophages stimulation and metalloprotease activity allowing tissue remodeling limiting sequels onset. Otherwise, healing altered in deficient G-CSF mice is corrected by the growth factor injection. The G-CSF is an immunomodulator whose activities appear to justify use in TEN : Polarization of immune response to Th2 non-cytotoxic (anti Th1), Preferential differentiation of naive LT (T lymphocytes) in regulator LT (CD25 high CD4+) and mobilization of regulator LT of the spinal cord to altered tissues. The G-CSF was used in a few cases of TEN with great efficacy. No data is available concerning sequels of SJS/TEN in treated patients. This clinical trial program, by providing proof of the efficacy of filgrastim in SJS/TEN, should allow progress in care of this serious toxics diseases. In the future, it could thus reduce the significant morbidity of these syndromes with a high rate of sequelae.

Condition or disease

Rare Diseases

Toxic Epidermal Necrolyses

Intervention/treatment

Filgrastim

Placebo

Phase

Phase 2

Phase 3

Study Type : Interventional
Estimated Enrollment : 42 participants
Masking: Double
Masking Description: This is a single blind patient trial. The outcomes assessor of the primary endpoint outcome, the adjudication committee and the statistician, will also be blinded to the allocated treatment.
Primary Purpose: Treatment
Official Title: Evaluating the Therapeutic Efficacy of Filgrastim in Severe Bullous Drug Eruptions (Lyell and Stevens-Johnson Syndromes)
Actual Study Start Date : September 1, 2021
Estimated Primary Completion Date : September 5, 2024
Estimated Study Completion Date : September 1, 2025
Arm Intervention/treatment

Experimental: FILGRASTIM

Standard symptomatic treatment of the SJS/NET (until the reepidermization of the patient) + [email protected] (30 MU/0,5mL and/or 48 MU/0,5mL - solution of 20 ml diluted in GLUCOSE 5%) administrated by IV or subcutaneous route over a period of 5 consecutive days (1 injection per day during 30 minutes)

Drug: Filgrastim

Placebo Comparator: PLACEBO

Standard symptomatic treatment of the SJS/NET (until the reepidermization of the patient) + 20 ml GLUCOSE 5% administrated by IV route over a period of 5 consecutive days (1 injection per day during 30 minutes)

Drug: Placebo

Ages Eligible for Study: 6 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria
  • Patient aged of 6 years old or more, presenting SJS/TEN, drug or infectious origin proofed and very strongly suspected (indirect certainty argument), confirmed by evaluator.
  • SJS or TEN evolving since less than 7 days with a progression of the detachment or the eruption observed dating less than 48 hours.
  • Patient and/or have right able to understand the objectives of the trial and having given their written consent to participate (parents for minors, have right for patients in immediate life-saving emergency).
  • Patient registered with a social security scheme or benefiting from a similar scheme.
  • Pregnancy test beta HCG negative for women of childbearing age
Exclusion Criteria
  • Patient weighing less than 20kg
  • Chronic myeloid pathology such as myeloid leukemia or AML (acute myeloid leukemia)
  • Thrombophilia or thrombotic pathology in progress
  • PNN (polymorphonuclear neutrophils) > 50.000 on the CBC (Complete Blood Count) during the inclusion visit
  • Patient who received cyclosporine, anti-TNFalpha or intravenous immunoglobulins or lithium in the month prior the inclusion
  • Pregnant or breastfeeding woman
  • Patient under protective measure (safeguard measure, curatorship, guardianship) or deprived of liberty
  • Patient in exclusion period after participation at other interventional clinical trial
  • Known hypersensitivity to the active substance (FILGRASTIM) or to the one of the excipients (glutamine acid, sorbitol E420, Polysorbate 80)
  • Patient presenting a known glucose intolerance or hereditary fructose intolerance
  • Patient with a traumatic brain injury less than 24 hours
  • Patient admitted with septic shock

Severe Bullous Drug Eruption and Filgrastim

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Severe Bullous Drug Eruption and Filgrastim

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Locations


Not yet recruiting

France,

Reference center for toxic bullous dermatoses and severe drug eruptions, Edouard Herriot Hospital, Hospices Civils de Lyon

Lyon, France, 69437

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