Severe Bullous Drug Eruption and Filgrastim

• Status: Not yet recruiting
• Trial end date: 2025-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hospices Civils de Lyon
• Treatments: Lenograstim

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