Topical Steroids Alone or Associated With Methotrexate in Bullous Pemphigoid
Information source: University Hospital, Montpellier
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Bullous Pemphigoid
Intervention: clobetasol propionate + Methotrexate (Drug); clobetasol propionate alone (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: University Hospital, Montpellier Official(s) and/or principal investigator(s): Olivier Dereure, MD, PhD, Principal Investigator, Affiliation: University of Montpellier France; French Society of Dermatology; french group for study of blistering diseases
Overall contact: Olivier Dereure, MD, PhD, Phone: 04 67 33 69 06, Ext: +33, Email: o-dereure@chu-montpellier.fr
Summary
This controlled multi-center randomized clinical trial, with direct individual benefit, will
compare efficacy and safety of two strategies in non-localized BP care: a combined regimen
using initial superpotent topical steroids associated with methotrexate for 4 weeks followed
by methotrexate alone for 8 months and superpotent topical steroids alone maintained 9
months (current standard of care). The expected result is an equivalence between the two
compared strategies in terms of safety and efficacy, MTX monotherapy during the maintenance
phase being easier to manage and therefore associated with better compliance than topical
steroids with less cutaneous side effects and most cost-effective.
Clinical Details
Official title: Comparison of Monotherapy With Protracted Superpotent Topical Steroids to Superpotent Topical Steroids Associated With Methotrexate in Bullous Pemphigoid
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: actuarial survival
Secondary outcome: Initial control rate of the diseaseSafety: The frequency of serious and significant adverse events Frequency of relapses Relapse-free survival Easiness of use
Detailed description:
Bullous pemphigoid (BP) is a rare mucocutaneous autoimmune bullous disorder (incidence
<1/10000 / year in France) that mostly affects elderly patients. Its mortality rate is as
high as 20 to 40% at one year. A study initiated by the French group for bulllous disorders
devoted to the study of autoimmune bullous diseases the study of autoimmune bullous diseases
and which is an international leader on this issue, has previously demonstrated the efficacy
and relatively good tolerance of superpotent topical corticosteroids in BP. However, the use
of superpotent topical corticosteroids is flawed with practical difficulties (home-based
care by nurses once or twice a day to administer treatment, this for several months) and its
cost is significantly higher than that an oral steroid treatment as a consequence. On the
other hand, there is probably a non-negligible systemic absorption of superpotent
topicalsteroid responsible for potentially serious side effects similar to those encountered
with systemic corticosteroids. Finally, a protracted treatment with superpotent topical
steroid most often causes skin atrophy with deleterious consequences. It would then be of
interest to be able to significantly reduce the duration of use of topical steroids through
an early-associated systemic treatment relying on an easy-to-use and relatively safe
molecule that would maintain the disease under control after an initial clinical remission
has been achieved by initial and time-limited use of superpotent topical steroids.
Methotrexate (MTX) could be an interesting candidate in this regard, with a low-level and
tolerable short- and middle-term toxicity if small doses are used (10-15 mg / week) while
its long-term safety is usually irrelevant in elderly patients. Its use and monitoring are
relatively easy and a number of international publications, including two recent French
ones, have shown efficacy in this setting including a relaying strategy after initial use of
superpotent topical steroids in BP treatment, in preliminary open studies .These encouraging
results prompt to propose a controlled multi-center randomized clinical trial, with direct
individual benefit, comparing efficacy and safety of a treatment regimen using superpotent
topical steroids alone maintained 9 months (current standard of care) to a mixed initial
treatment combining applications of superpotent topical steroids associated with
methotrexate for 4 weeks followed by methotrexate alone for 8 additional months in
non-localized BP. In both arms, the total treatment duration will then be 9 months. The two
arms of the study will be: Arm A: daily applications of topical clobetasol propionate at a
dose of 10 to 30 g / day depending on the patient's weight and the initial number of new
blisters per day, associated with methotrexate (MTX) received either orally or
subcutaneously at a dose of 12. 5 mg / week in patients weighing less than 60 kg and with
creatinine clearance greater than 50 ml / min (planned dose reduction to 10 mg / week in
patients less than 60 kg or with a creatinine clearance less than 50 ml / min) for four
weeks followed by oral or subcutaneous methotrexate alone at the same dose during following
8 monthsArm B: daily applications of topical clobetasol propionate at a dose of 10 to 30 g /
day depending on the patient's weight and the initial number of new blisters per day
maintained until 14 days after full disease control followed by the same daily dose applied
every other day for a month and then twice a week for a month and then once a week until the
end of the 9th month. The primary endpoint will be the actuarial survival rate at one year in
both groups and secondary endpoints will be the initial control rate of the disease, the
number of serious side effects during treatment and the number of relapses during
treatment. The expected result is an equivalence between the two compared strategies in
terms of safety and efficacy, MTX monotherapy during the maintenance phase being easier to
manage and therefore associated with better compliance than topical steroids with less
cutaneous side effects and most cost-effective. This study will enroll 150 patients per arm
and will include a follow up of 9 months with 9 visits per patient.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Subjects aged 18 years old or more
- Patients affiliated to social security system,
- Bullous pemphigoid diagnosed according to the following criteria: presence of at
least 3 of the 4 clinical criteria for bullous pemphigoid as published by the french
group for study of blistering diseases (positive predictive value: 95 %: age over 70
years, no lesions on neck or head, absence of atrophic scars, no mucosal lesions.=
Histological Examination consistent with BP diagnosis and carried out in the month
before inclusion: existence of a sub epidermal blister regardless of its size,
containing neutrophils and / or eosinophils associated with a dermal infiltrate
consisting of neutrophils and / or eosinophils, or to margination of neutrophils and
/ or eosinophils along the dermoepidermal junction.= Direct immunofluorescence
performed (DIF) in the month preceding inclusion and showing linear deposition of IgG
and / or C3 along the dermo-epidermal junction.
- Patients: = no prior topical steroid or superpotent topical steroids for less than
16 days using the same or equivalent dosage as the one used in the study a
different regimen and this regardless of the clinical resultsOR receiving potent or
superpotent topical steroids for at least 16 days with a different regimen than that
used during the trial AND not controlled by this treatment (appearance of at least 3
new blisters per day)
- written consent of the patient or, if not possible, certified by a third party,
- effective contraception (oral or intrauterine device) set up at least one month
before inclusion for women of childbearing age,
- For women of reproductive age (age <50 years), negative serum pregnancy test at
inclusion
- Serum albumin ≥ 25 g / L
Exclusion Criteria:
- Localized bullous pemphigoid (area <400 cm2: 20 x 20 cm)
- Major blood cytopenia: Hb ≤ 10 g / dl and / or leukocytes ≤ 3000 / mm3 and / or
platelets ≤ 100,000 / mm3
- Creatinine Clearance appreciated by the formula MDRD <30 ml / min
- Serum albumin <25 g / L
- pregnancy-associated Pemphigoid
- Linear IgA Dermatosis identified by DIF
- Pemphigoid with clinically dominant mucosal lesions
- Relapse of previously diagnosed pemphigoid and still receiving treatment or for whom
treatment was stopped for less than six months
- Known allergy to topical steroids and / or methotrexate
- recent history of liver disease (within two years) regardless of its nature or
presence of active liver disease (transaminases and / or alkaline phosphatase greater
than twice the upper standard laboratory)
- Chronic alcoholism (declared consumption of more than 60 g alcohol / day or
approximately 0. 5 L / day of wine)
- patient receiving notoriously hepatotoxic drugs or that can interfere with metabolism
or haematological toxicity of Methotrexate
- Peptic ulcer proven by endoscopy performed during the last 15 days
- Severe Active infection regardless of its nature
- Evolutive neoplasia whatever its nature except basal cell carcinoma
- Poorly controlled diabetes mellitus (fasting glucose greater than or equal to 2 2. 5 g
/ L and / or Hb A1C greater than or equal to 8. 5% before treatment)
- disease that can not be possibly monitored on a regular basis
- acquired or congénital Immunosuppression
- known HIV Seropositivity
- Chronic respiratory failure
- Pregnancy or breastfeeding
- Patient of childbearing age and not using effective contraception
- Patient incapable of giving informed consent and for whom a family member or a
trustworthy third party does not grant participation in the study, protected adults,
vulnerable people (art. L1121-6, L1121-7, L 1121-8, L1121-9) or patient accrued in
another clinical research study
- Long-term treatment prescribed for another illness by steroids, immunosuppressive
drugs, cyclosporin or any other treatment that may have been successfully used in the
treatment of bullous pemphigoid (dapsone, Gamma globulins, plasma exchange,
tetracyclines). For all previous medications, a minimum clearance of two months is
required before enrollment in the present trial
Locations and Contacts
Olivier Dereure, MD, PhD, Phone: 04 67 33 69 06, Ext: +33, Email: o-dereure@chu-montpellier.fr
University Hospital Of Montpellier, Montpellier 34295, France; Recruiting Olivier Dereure, MD, PhD, Phone: 04 67 33 69 06, Ext: +33, Email: o-dereure@chu-montpellier.fr Olivier Dereure, MD, PhD, Principal Investigator
Additional Information
Starting date: January 2008
Last updated: December 11, 2014
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