DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Comparison Between Corticosteroid and Topical Steroids in the DRESS

Information source: Assistance Publique - Hpitaux de Paris
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Drug Rash With Eosinophilia and Systemic Symptoms

Intervention: Prednisone (Drug); Clobetasol (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Assistance Publique - Hpitaux de Paris

Official(s) and/or principal investigator(s):
Olivier CHOSIDOW, MD, PhD, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris

Overall contact:
Olivier CHOSIDOW, MD, PhD, Phone: (0) 149812501, Ext: +33, Email: olivier.chosidow@hmn.aphp.fr

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.

Clinical Details

Official title: DRESS - Setting of Corticosteroid Treatment.

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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.

Secondary outcome:

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

Delays of complete or almost complete visceral healing

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

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

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

Mortality rate at Month 12

Sequelae rate at Month 12

Systemic steroids adverse reactions rate

Topical steroids adverse reactions rate

Patch tests evaluation in DRESS

Reactivation kinetics of Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Herpes Simplex virus (HSV), Human Herpes virus6 (HHV6) and Human Herpes virus7 (HHV7)

Predictive value of lymphocyte transformation test in imputability

Immunological factors evaluation in the skin

Blood inflammatory cytokines and chemokines analysis

Blood cytokines polymorphisms analysis

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 ° 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

- 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

Locations and Contacts

Olivier CHOSIDOW, MD, PhD, Phone: (0) 149812501, Ext: +33, Email: olivier.chosidow@hmn.aphp.fr

Henri Mondor Hospital, Creteil 94010, France; Recruiting
Olivier CHOSIDOW, MD, PhD, Phone: (0)149812501, Ext: +33, Email: olivier.chosidow@hmn.aphp.fr
Laetitia GREGOIRE, M.Sc, Phone: (0)149814164, Ext: +33, Email: laetitia.gregoire@hmn.aphp.fr
Olivier CHOSIDOW, MD, PhD, Principal Investigator
Additional Information

Related publications:

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.

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.

Starting date: October 2013
Last updated: July 29, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017