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

Assistance Publique - Hôpitaux de Paris

Status

Unknown

Conditions

Drug Rash With Eosinophilia and Systemic Symptoms

Treatments

Drug: Prednisone

Drug: Clobetasol

Study type

Interventional

Funder types

Other

Identifiers

NCT01987076

2012-001471-36 (EudraCT Number)

P110108

Details and patient eligibility

About

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.

Enrollment

112 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 ° at the time of examination or fever ≥ 38.5 ° peak in the last 72 hours (amendment 2 : ANSM + CPP : 08/04/14)
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 ≥ 4 ULN and < 15 ULN and/or PAL ≥5 ULN and V factor 50% (amendment 2 : ANSM + CPP : 08/04/14)
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 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)
Severe dermatitis perioral cont-indicating the use of corticosteroid
Severe acne contra-indicating the use of a corticosteroid
Pregnant or nursing women