Drug Rash With Eosinophilia and Systemic SymptomsDRESSCODENCT01987076
Comparison Between Corticosteroid and Topical Steroids in the DRESS
A study testing Prednisone and Clobetasol in people with Drug Rash With Eosinophilia and Systemic Symptoms, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Drug Rash With Eosinophilia and Systemic Symptoms
- What is being tested?
- Prednisone and Clobetasol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2013to Oct 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 :
Show all 26Show fewer
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Henri Mondor Hospital
Créteil, 94010
Olivier CHOSIDOW, MD, PhD, (0)149812501 ext. +33, olivier.chosidow@hmn.aphp.fr
Laetitia GREGOIRE, M.Sc, (0)149814164 ext. +33, laetitia.gregoire@hmn.aphp.fr
About this study
Official title: DRESS - Setting of Corticosteroid Treatment.
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.
- Being tested
- Prednisone, Clobetasol
- Keywords
- DRESS, Systemic steroid, Topical steroid, Treatment
- Medical subject headings
- Drug Hypersensitivity Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrednisoneDrug
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.
ClobetasolDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Corticosteroids per os: Prednisone + Emollient | Active comparator | Not described Receives: Drug: Prednisone |
| Topical corticosteroid: Clobetasol + Emollient | Experimental | Not described Receives: Drug: Clobetasol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: Day 30
Delays of complete or almost complete visceral healing
Measured: Month 12
Relapse rates and bounces rates between the end of acute treatment and M12
Measured: Month 12
Patients rate evaluating to severe form (occurrence of a criterion defining the severe form cf. Above)
Measured: Month 12
Occurrence rate of moderate DRESS visceral involvement, during the initial treatment (D0 to D30) not existing at inclusion
Measured: Day 30
Mortality rate at Month 12
Measured: Month 12
Sequelae rate at Month 12
Measured: Month 12
Systemic steroids adverse reactions rate
Measured: Month 12
Topical steroids adverse reactions rate
Measured: Month 12
Patch tests evaluation in DRESS
Measured: Month 6
Reactivation kinetics of Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Herpes Simplex virus (HSV), Human Herpes virus6 (HHV6) and Human Herpes virus7 (HHV7)
Measured: Day 0, Day 7, Day 14, Day 21, Day 30, Month 3, Month 6, Month 12
Predictive value of lymphocyte transformation test in imputability
Measured: Day 0, Day 30, Month 6, Month 12
Immunological factors evaluation in the skin
Measured: Day 30
Blood inflammatory cytokines and chemokines analysis
Measured: Day 0, Day 30, Month 6
Blood cytokines polymorphisms analysis
Measured: Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2013 (estimated)
- Study startOct 2013
- Primary completionOct 2015 (estimated)
- Study completionOct 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Drug Rash With Eosinophilia and Systemic SymptomsStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olivier CHOSIDOW, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01987076
- Sponsor's protocol ID
- P110108
- Other IDs
- 2012-001471-36
- Acronym
- DRESSCODE
- Status last verified
- Jul 2015
- First submitted
- 17 Sep 2013
- Last updated
- 30 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 19153346Mardivirin 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.
PubMed 19822481Ingen-Housz-Oro S, Guichard E, Milpied B, Bensaid B, Collet E, Barbaud A, Le Duff F, Tetart F, Soria A, Machet L, Descamps V, Monestier S, Pasteur J, Morice C, Chaby G, Colin A, Gregoire L, Allanore L, Giraudeau B, Chosidow O. Topical versus oral corticosteroids in moderate drug reaction with eosinophilia and systemic symptoms: A multicenter randomized clinical trial. J Am Acad Dermatol. 2024 Sep;91(3):544-547. doi: 10.1016/j.jaad.2024.04.077. Epub 2024 May 14. No abstract available.
PubMed 38754628Funck-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.
PubMed 25592341
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DRESS - Setting of Corticosteroid Treatment.
- ClinicalTrials.gov ID
- NCT01987076
- Acronym / sponsor ID
- DRESSCODE / P110108
- Keywords
- DRESS, Systemic steroid, Topical steroid, Treatment
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Oct 2015 (estimated)
- Study completion
- Oct 2016 (estimated)
- First posted
- 19 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Corticosteroids per os: Prednisone + Emollient | Active comparator | Drug: Prednisone |
| Topical corticosteroid: Clobetasol + Emollient | Experimental | Drug: Clobetasol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- patient age ≥ 18 years
- signing informed consent form
- DRESS diagnosis with at least 4 criteria a, b, c, d
- 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
Key exclusion criteria (18 listed)
- 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 :
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrednisonePrednisone: 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. | Drug | Corticosteroids per os: Prednisone + Emollient |
| ClobetasolClobetasol: 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 | Drug | Topical corticosteroid: Clobetasol + Emollient |
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.
Time frame: Day 30
15 secondary outcomes
Rate of patients with a complete or almost complete healing of cutaneous and visceral involvement at Day 30 ± 5 days
Time frame: Day 30
Delays of complete or almost complete visceral healing
Time frame: Month 12
Relapse rates and bounces rates between the end of acute treatment and M12
Time frame: Month 12
Patients rate evaluating to severe form (occurrence of a criterion defining the severe form cf. Above)
Time frame: Month 12
Occurrence rate of moderate DRESS visceral involvement, during the initial treatment (D0 to D30) not existing at inclusion
Time frame: Day 30
Mortality rate at Month 12
Time frame: Month 12
Sequelae rate at Month 12
Time frame: Month 12
Systemic steroids adverse reactions rate
Time frame: Month 12
Topical steroids adverse reactions rate
Time frame: Month 12
Patch tests evaluation in DRESS
Time frame: Month 6
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
Predictive value of lymphocyte transformation test in imputability
Time frame: Day 0, Day 30, Month 6, Month 12
Immunological factors evaluation in the skin
Time frame: Day 30
Blood inflammatory cytokines and chemokines analysis
Time frame: Day 0, Day 30, Month 6
Blood cytokines polymorphisms analysis
Time frame: Month 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2015.
- Background: PubMed 19153346Eshki 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.
- Background: PubMed 19822481Mardivirin 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.
- Derived from this study: PubMed 38754628Ingen-Housz-Oro S, Guichard E, Milpied B, Bensaid B, Collet E, Barbaud A, Le Duff F, Tetart F, Soria A, Machet L, Descamps V, Monestier S, Pasteur J, Morice C, Chaby G, Colin A, Gregoire L, Allanore L, Giraudeau B, Chosidow O. Topical versus oral corticosteroids in moderate drug reaction with eosinophilia and systemic symptoms: A multicenter randomized clinical trial. J Am Acad Dermatol. 2024 Sep;91(3):544-547. doi: 10.1016/j.jaad.2024.04.077. Epub 2024 May 14. No abstract available.
- Derived from this study: PubMed 25592341Funck-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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier CHOSIDOW, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Prednisone and Clobetasol in people with Drug Rash With Eosinophilia and Systemic Symptoms, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Olivier CHOSIDOW, MD, PhD ((0) 149812501 ext. +33, olivier.chosidow@hmn.aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01987076, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2015; AzTrials last refreshed its copy on 6 Nov 2026.