Comparison Between Corticosteroid and Topical Steroids in the DRESS (DRESSCODE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01987076
First received: September 17, 2013
Last updated: November 12, 2013
Last verified: September 2013
  Purpose

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe multiorgan adverse drug reaction occurring within 2 to 6-8 weeks after a new drug intake. DRESS syndrome is defined by the combination of clinical manifestations, cutaneous, visceral and biological disturbances. Its prognosis is directly linked to severity of visceral involvement, with a mortality evaluated above 10%.

Considering curative treatment, there is no consensus. Until now, no controlled trial has been performed. Systemic steroids are mainly used in first intention, in particular for management of visceral involvements, whatever their severity. From clinical practice, topical steroids are often used and could be helpful in the therapeutic management of DRESS.

We propose to evaluate systemic steroids versus very potent topical steroids in a multicentric randomized controlled trial including defined moderate DRESS, ie the non-inferiority of very potent topical steroids in terms of remission of visceral involvement at Day30 and the superiority of very potent topical steroids in terms of delay to remission of skin involvement.


Condition Intervention
Drug Rash With Eosinophilia and Systemic Symptoms
Drug: Prednisone
Drug: Clobetasol

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: DRESS - Setting of Corticosteroid Treatment.

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Rate of patients with a complete or almost healing of visceral involvement to D30 +/- 5 days AND complete or almost complete healing of skin involvement. [ Time Frame: Day 30 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of patients with a complete or almost complete healing of cutaneous and visceral involvement at Day 30 ± 5 days [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
  • Delays of complete or almost complete visceral healing [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  • Relapse rates and bounces rates between the end of acute treatment and M12 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  • Patients rate evaluating to severe form (occurrence of a criterion defining the severe form cf. Above) [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  • Occurrence rate of moderate DRESS visceral involvement, during the initial treatment (D0 to D30) not existing at inclusion [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
  • Mortality rate at Month 12 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  • Sequelae rate at Month 12 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  • Systemic steroids adverse reactions rate [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  • Topical steroids adverse reactions rate [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  • Patch tests evaluation in DRESS [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
  • Reactivation kinetics of Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Herpes Simplex virus (HSV), Human Herpes virus6 (HHV6) and Human Herpes virus7 (HHV7) [ Time Frame: Day 0, Day 7, Day 14, Day 21, Day 30, Month 3, Month 6, Month 12 ] [ Designated as safety issue: No ]
  • Predictive value of lymphocyte transformation test in imputability [ Time Frame: Day 0, Day 30, Month 6, Month 12 ] [ Designated as safety issue: No ]
  • Immunological factors evaluation in the skin [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
  • Blood inflammatory cytokines and chemokines analysis [ Time Frame: Day 0, Day 30, Month 6 ] [ Designated as safety issue: No ]
  • Blood cytokines polymorphisms analysis [ Time Frame: Month 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 112
Study Start Date: September 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Corticosteroids per os: Prednisone + Emollient (Dexeryl*) Drug: Prednisone

Prednisone:

Day 0 to day 30: 0.5mg/kg/day Day 30 to day 180: doses decreasing from 15 to 25% every 15 days until Day75 and 10 to 15% every 15 days.

Experimental: Topical corticosteroid: Clobetasol + Emollient (Dexeryl*) Drug: Clobetasol
Clobetasol: cream 0.05% Day 0 to day 30: 30 grams per day Day 30 to day 45: 20 grams per day Day 45 to day 60: 20 grams every other day Day 60 to day 120: 20 grams biweekly Day 120 to day 150: 20 grams one a week

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patient age ≥ 18 years
  • signing informed consent form
  • DRESS diagnosis with at least 4 criteria a, b, c, d

    1. Skin rash occurring at least 10 days and not more than two months after continuous drug intake (or within less than 10 days in case of rechallenge)
    2. fever ≥ 38.5° above
    3. at least one visceral compatible :
  • lymphadenopathy on at least two different sites measuring at least 1 cm in diameter
  • transaminases > 2 upper limit of normal (ULN) or alkaline phosphatise > 3 ULN
  • lung involvement defined by hypoxemia (capillary oximetry ≤ 95%) and/or interstitial lung disease on chest radiography or scanner, in absence of other lung disease
  • myocarditis, pericarditis (ECG clinical suspicion and confirmed by echocardiography)
  • renal impairment defined as creatinine increase above the normal laboratory value associated with leucocyturia > 1000 / mm3 or proteinuria, a Na / K ratio >1 and Urine Cyto-bacteriology (EBCU) sterile in the absence of preexisting renal disease d) At least one of the following haematological abnormalities:
  • eosinophilia ≥ 0.7 g/l or > 10 % absolute
  • lymphocytosis ≥ 5*10^9 /l
  • presence of atypical blood lymphocytes
  • Patient with moderate DRESS : defined by at least one reached as follows :
  • pulmonary: interstitial pneumonia with oxygen partial pressure in arterial blood (PaO2) 60-75 mmHg without dyspnoea at rest
  • Hepatic: transaminases ≥ 5 ULN and < 15 ULN and/or PAL ≥10 ULN and V factor 50%
  • renal :
  • acute renal failure and organic sharp increase in the 48 hours preceding the inclusion of more of 26.4 micromol/l creatinine
  • and / or increase of 1.5 times the normal creatinine value
  • and / or decrease of oliguria of less than 0.5 ml/kg/h followed by a 6 hours
  • cord: pancytopenia (7≤Hb≤10 gr/dl and/or 50<p<100 G/L, 0.5<PNN≤1.5G/l)
  • AND absence of cardiac, neurological or gastrointestinal (gut, pancreas) threatening
  • Drug withdrawal
  • Patient with health insurance (or entitled beneficiary)
  • Patient accepting the constraints of the test

Exclusion Criteria:

  • uncontrolled sepsis
  • unability to discontinue the medication(s) due
  • known hypersensitivity to systemic or topical corticosteroids
  • hepatitis B or C known, active HIV status known
  • Patient already treated by corticosteroid :

    • More than 48 hours
    • Less than 48 hours to following conditions :
  • Patients receiving more than 1 mg/kg/day of prednisone per os
  • Patients receiving methylprednisolone pulse up to 1mg/kg prednisone equivalent
  • Patients receiving more than 30 grams per day level 3 topical steroid or more than 10 grams per day level 4 topical steroid
  • Patient undergoing immunosuppressive therapy for another disease
  • Participation in another drug biomedical research
  • Primitive bacterial infections, fungal or parasitic
  • Severe rosacea cont-indicating the use of corticosteroid
  • Presence of at least one ulcerated lesion (more than 10cm2)
  • Severe dermatitis perioral cont-indicating the use of corticosteroid
  • Severe acne contra-indicating the use of a corticosteroid
  • Pregnant or nursing women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01987076

Contacts
Contact: Olivier CHOSIDOW, MD, PhD (0) 149812501 ext +33 olivier.chosidow@hmn.aphp.fr
Contact: : Laurence ALLANORE, MD (0) 149812501 ext +33 laurence.allanore@hmn.aphp.fr

Locations
France
Henri Mondor Hospital Recruiting
Creteil, France, 94010
Contact: Olivier CHOSIDOW, MD, PhD    (0)149812501 ext +33    olivier.chosidow@hmn.aphp.fr   
Contact: Laetitia GREGOIRE, M.Sc    (0)149814164 ext +33    laetitia.gregoire@hmn.aphp.fr   
Principal Investigator: Olivier CHOSIDOW, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Olivier CHOSIDOW, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

Publications:
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01987076     History of Changes
Other Study ID Numbers: P110108, 2012-001471-36
Study First Received: September 17, 2013
Last Updated: November 12, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
DRESS
Systemic steroid
Topical steroid
Treatment

Additional relevant MeSH terms:
Drug Hypersensitivity
Drug Eruptions
Eosinophilia
Dermatitis
Skin Diseases
Hypersensitivity
Immune System Diseases
Drug Toxicity
Poisoning
Substance-Related Disorders
Leukocyte Disorders
Hematologic Diseases
Clobetasol
Prednisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 23, 2014