Effectivity of alitretinoin compared to azathioprine in patients with severe chronic non-hyperkeratotic hand eczema.
- Conditions
- Hand eczemaTherapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2015-001447-37-NL
- Lead Sponsor
- niversity Medical Center Groningen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Age = 18 years and = 75 years
- Severe chronic non-hyperkeratotic hand eczema for a minimum duration of 3 months as defined by a Physician Global Assessment (PGA) using a validated Photoguide
- Refractory to standard therapy, defined as:
-> Patients received treatment with topical corticosteroids of class II or higher for at least 8 weeks within 3 months before enrolment, with either no response or a transient response
-> Patients had also received standard skin care, including emollients and barrier protection as appropriate, without significant improvement
-> Patients had avoided irritants and allergens, if identified, without significant improvement
- Women of childbearing potential are required to use at least two forms of contraception for at least 1 month before starting treatment, during treatment, and for at least 1 month after finishing treatment; these women are required to take monthly pregnancy tests
- Not previously treated with alitretinoin or azathioprine
- Able to provide written informed consent
- Able to speak and read the Dutch language
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16
A potential subject who meets any of the following criteria will be excluded from participation in this study:
General criteria prior to randomization
- Hyperkeratotic palmar eczema as defined by the Danish Contact Dermatitis Group
- Patients with predominantly atopic dermatitis, in which the hands are also involved. Patients with mild atopic dermatitis, in which the hands are mainly affected are eligible for inclusion.
- Psoriasis
- Active bacterial, fungal, or viral infection of the hands
- Pregnant/lactating or planning to become pregnant during the study period
- Treatment with systemic medication or UV radiation within the previous 4 weeks
- Use of topical corticosteroids > class II within 1 week before enrolment
- Mentally incompetent
- Currently active depression
- Immunocompromised status
- Known or suspected allergy to ingredients in the study medications
- Inclusion in a study of an investigational drug within 60 days prior to start of treatment
- Current malignancy (other than successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix)
- Current active pancreatitis
- Living vaccine (including bacillus Calmette-Guérin (BCG), varicella, measles, mumps, rubella, yellow fever, oral polio and oral typhoid) in the last 2 weeks or the planned application of such a vaccine during the study period
- Evidence of alcohol abuse or drug addiction
- Chronic or recurrent infectious diseases
- Contact sensitizations with clinical relevance to the hands, in which avoidance of exposure is unclear
- Hypervitaminosis A due to the use of vitamin A supplements containing >2000 IU
- Use of drugs with potential to change the effective dosis of study drugs within the previous 2 weeks
Laboratory exclusion criteria post randomization
- Alanine aminotransferase (ALAT) and /or aspartate aminotransferase (ASAT) values > 200% of the upper limit of normal
- Impaired renal function as indicated by a clinically relevant abnormal creatinine value (to be determined by investigator or treating physician)
- Anemia as indicated by a clinically relevant lowered hemoglobin value (to be determined by investigator or treating physician)
Alitretinoin specific
- Triglycerides > 200% of the upper limit of normal,
- Cholesterol or low density lipoprotein (LDL) cholesterol values > 200% of the upper limit of normal
- Uncontrolled hypothyroidism (to be determined by investigator or treating physician)
Azathioprine specific
- Patients with low or absent thiopurine methyltransferase (TPMT) activity (defined in our center as <52 nmol/gHb/hour, combined with genotyping showing homozygous of compound heterozygous mutations) and a subsequent risk for life-threatening myelotoxicity
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): The primary endpoint for efficacy is response to treatment, defined as an improvement of = 2 steps on the Physician Global Assessment (PGA), developed by Ruzicka et al, after 24 weeks of treatment. ;Timepoint(s) of evaluation of this end point: 24 weeks;Main Objective: To compare the efficacy of alitretinoin and azathioprine in the treatment of severe chronic non-hyperkeratotic hand eczema.;Secondary Objective: To compare time to response, to compare health related quality of life, to compare improvement in severity of hand eczema assessed by the patient, to compare safety.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary endpoints are improvement in: mean PGA after 12 and 24 weeks, the Hand Eczema Severity Index (HECSI) score, the Health related QoL questionnaire for hand eczema (QOLHEQ), and a Patient Global Assessement (PaGA) of improvement. Adverse events will be registered, as well as time to response.;Timepoint(s) of evaluation of this end point: Improvement in:<br>Mean PGA: 12 and 24 weeks.<br>HECSI: 4, 8, 12 and 24 weeks.<br>QOLHEQ: 12 and 24 weeks.<br>PaGA: 12 and 24 weeks.<br>Adverse events and time to response at every visit.