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Severe Bullous Drug Eruption and Filgrastim
Sponsor: Hospices Civils de Lyon
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.
Official title: Evaluating the Therapeutic Efficacy of Filgrastim in Severe Bullous Drug Eruptions (Lyell and Stevens-Johnson Syndromes)
Key Details
Gender
All
Age Range
6 Years - Any
Study Type
INTERVENTIONAL
Enrollment
42
Start Date
2022-05-13
Completion Date
2026-05-13
Last Updated
2024-05-08
Healthy Volunteers
No
Conditions
Interventions
Filgrastim
Injection of ZARZIO 30 MU/0,5mL and/or ZARZIO 48 MU/0,5mL, over a period of 5 consecutive days (1 injection per day during 30 minutes - - day 1 : set up standard treatment). The filgrastim solution will be diluted in 20 mL of 5% Glucose. The dose of ZARZIO administrated depends of the patient's weight : * 20 to \< 30kg = 0,3 mL of ZARZIO 48 MU/0,5mL (subcutaneous route) * 30 to \< 60kg = 0,5 mL of ZARZIO 30 MU/0,5mL (by IV) * 60 to \< 90kg = 0,5 mL of ZARZIO 48 MU/0,5mL (by IV) * 90 to \< 120kg = 2x0,5 mL of ZARZIO 30 MU/0,5mL (by IV) * 120 to 150kg = 0,5 mL of ZARZIO 30 MU/0,5mL + 0,5 mL of ZARZIO 48 MU/0,5mL (by IV) * \> 150kg = 2x0,5 mL of ZARZIO 48 MU/0,5mL (by IV)
Placebo
Injection of 20 mL of Glucose 5% solution over a period of 5 consecutive days (1 injection per day during 30 minutes - day 1 : set up standard treatment). The dose given is equivalent to that used for filgrastim : * 20 to \< 30kg = placebo not available because the injection must be done subcutaneously so the blind cannot be respected. * 30 to \< 60kg = 20mL of Glucose 5% solution (by IV) * 60 to \< 90kg = 20mL of Glucose 5% solution (by IV) * 90 to \< 120kg = 20mL of Glucose 5% solution (by IV) * 120 to 150kg = 20mL of Glucose 5% solution (by IV) * \> 150kg = 20mL of Glucose 5% solution (by IV)
Locations (3)
Département d'Anesthésie-Réanimation , Hôpital Edouard Herriot, Hospices Civils de Lyon
Lyon, France
Reference center for toxic bullous dermatoses and severe drug eruptions, Edouard Herriot Hospital, Hospices Civils de Lyon
Lyon, France
Service de Médecine Interne, Hôpital Edouard Herriot, Hospices Civils de Lyon
Lyon, France