Efficacy of oral alitretinoin versus oral azathioprine in patients with severe chronic non-hyperkeratotic hand eczema. A randomized prospective open-label trial with blinded outcome assessment.
- Conditions
- hand eczema10014982
- Registration Number
- NL-OMON41737
- Lead Sponsor
- niversitair Medisch Centrum Groningen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 116
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;- Able to provide written informed consent;- Able to speak and read the Dutch language
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
- Mentally incompetent
- 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 exposure to allergens is not avoided
- 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint for efficacy is response to treatment, defined as an<br /><br>improvement of * 2 steps on the Physician Global Assessment (PGA), developed by<br /><br>Ruzicka et al, after 24 weeks of treatment. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints are improvement in: mean PGA after 12 and 24 weeks, the<br /><br>Hand Eczema Severity Index (HECSI) score, the Health related QoL questionnaire<br /><br>for hand eczema (QOLHEQ), and a Patient Global Assessement (PaGA) of<br /><br>improvement. Adverse events will be registered, as well as time to response.<br /><br>Furthermore cost-utility, quality adjusted life years (QALYs) and<br /><br>cost-effectiveness will be assessed with the EQ-5D-5L questionnaire while<br /><br>monitoring treatment related costs.</p><br>