Comparison Between Corticosteroid and Topical Steroids in the DRESS

NCT01987076 | Unknown DMC

• 2 other identifiers: P1101082012-001471-36
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug Rash With Eosinophilia and Systemic Symptoms

Keywords

DRESS; Systemic steroid; Topical steroid; Treatment

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 30

Secondary Outcomes (15)

• Rate of patients with a complete or almost complete healing of cutaneous and visceral involvement at Day 30 ± 5 days

  Day 30

• Delays of complete or almost complete visceral healing

  Month 12

• Relapse rates and bounces rates between the end of acute treatment and M12

  Month 12

• Patients rate evaluating to severe form (occurrence of a criterion defining the severe form cf. Above)

  Month 12

• Occurrence rate of moderate DRESS visceral involvement, during the initial treatment (D0 to D30) not existing at inclusion

  Day 30

Study Arms (2)

Corticosteroids per os: Prednisone + Emollient

ACTIVE COMPARATOR

Drug: Prednisone

Topical corticosteroid: Clobetasol + Emollient

EXPERIMENTAL

Drug: Clobetasol

Interventions

Prednisone DRUG

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.

Corticosteroids per os: Prednisone + Emollient

Clobetasol DRUG

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

Topical corticosteroid: Clobetasol + Emollient

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patient age ≥ 18 years
• signing informed consent form
• DRESS diagnosis with at least 4 criteria a, b, c, d
• 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)
• Fever ≥ 38 ° at the time of examination or fever ≥ 38.5 ° peak in the last 72 hours (amendment 2 : ANSM + CPP : 08/04/14)
• 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 :

You may not qualify if:

• 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 suppressed by amendment 5 : ANSM16/04/2015 and CPP 07/04/2015)
• (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 --\> suppressed by amendment 3 : ANSM 28/05/14 CPP : 10/06/14)
• (Patient undergoing immunosuppressive therapy for another disease suppressed by amendment 5 : ANSM16/04/2015 and CPP 07/04/2015)
• 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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Henri Mondor Hospital

Créteil, 94010, France

RECRUITING

Related Publications (3)

• Eshki M, Allanore L, Musette P, Milpied B, Grange A, Guillaume JC, Chosidow O, Guillot I, Paradis V, Joly P, Crickx B, Ranger-Rogez S, Descamps V. Twelve-year analysis of severe cases of drug reaction with eosinophilia and systemic symptoms: a cause of unpredictable multiorgan failure. Arch Dermatol. 2009 Jan;145(1):67-72. doi: 10.1001/archderm.145.1.67.

  PMID: 19153346 BACKGROUND

• Mardivirin L, Valeyrie-Allanore L, Branlant-Redon E, Beneton N, Jidar K, Barbaud A, Crickx B, Ranger-Rogez S, Descamps V. Amoxicillin-induced flare in patients with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms): report of seven cases and demonstration of a direct effect of amoxicillin on Human Herpesvirus 6 replication in vitro. Eur J Dermatol. 2010 Jan-Feb;20(1):68-73. doi: 10.1684/ejd.2010.0821. Epub 2009 Oct 12.

  PMID: 19822481 BACKGROUND

• Funck-Brentano E, Duong TA, Bouvresse S, Bagot M, Wolkenstein P, Roujeau JC, Chosidow O, Valeyrie-Allanore L. Therapeutic management of DRESS: a retrospective study of 38 cases. J Am Acad Dermatol. 2015 Feb;72(2):246-52. doi: 10.1016/j.jaad.2014.10.032.

  PMID: 25592341 DERIVED

MeSH Terms

Conditions

Drug Hypersensitivity Syndrome

Interventions

Prednisone; Clobetasol

Condition Hierarchy (Ancestors)

Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Betamethasone; Steroids, Fluorinated

Study Officials

• Olivier CHOSIDOW, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olivier CHOSIDOW, MD, PhD

CONTACT

(0) 149812501; olivier.chosidow@hmn.aphp.fr

: Laurence ALLANORE, MD

CONTACT

(0) 149812501; laurence.allanore@hmn.aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2013
• First Posted: November 19, 2013
• Study Start: October 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2016
• Last Updated: July 30, 2015

Record last verified: 2015-07

Locations

FR (1)