Severe Bullous Drug Eruption and Filgrastim

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Brief Title

Severe Bullous Drug Eruption and Filgrastim

Official Title

Evaluating the Therapeutic Efficacy of Filgrastim in Severe Bullous Drug Eruptions (Lyell and Stevens-Johnson Syndromes)

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.
    


Study Phase

Phase 2/Phase 3

Study Type

Interventional


Primary Outcome

Arrest of the SJS/NET progression at day 5

Secondary Outcome

 Arrest of the SJS/NET progression

Condition

Rare Diseases

Intervention

Filgrastim

Study Arms / Comparison Groups

 FILGRASTIM
Description:  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)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

42

Start Date

September 1, 2021

Completion Date

September 1, 2025

Primary Completion Date

September 5, 2024

Eligibility 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
      

Gender

All

Ages

6 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, 472 117 211, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT04651439

Organization ID

69HCL19_0375


Responsible Party

Sponsor

Study Sponsor

Hospices Civils de Lyon


Study Sponsor

, , 


Verification Date

June 2021