Clinical trial NCT03026907: Alitretinoin vs Azathioprine in Severe Non-hyperkeratotic Hand Eczema
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hand Eczema
Keywords: Alitretinoin
Azathioprine
Hand eczema
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2017-01-20
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the efficacy of alitretinoin and azathioprine in the treatment of patients with severe chronic non-hyperkeratotic hand eczema.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years and ≤ 75 years
* Severe or very 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

Exclusion Criteria:

General criteria prior to randomization

* Treatment with alitretinoin or azathioprine in the previous 3 months
* 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

Primary outcomes:
measure: Response to treatment/hand eczema severity (Photoguide)
timeFrame: 24 weeks (end of treatment)
Secondary outcomes:
measure: Response to treatment/hand eczema severity (Photoguide)
timeFrame: 12 weeks
measure: Response to treatment/hand eczema severity (Hand Eczema Severity Index, HECSI)
timeFrame: Week 4, 8, 12, 24
measure: Time to response
timeFrame: Week 4, 8, 12, 24
measure: Patient reported improvement (Patient Global Assessment, PaGA)
timeFrame: Week 12 and 24
measure: Safety and tolerability (adverse events)
timeFrame: Up to 24 weeks
measure: Cost-utility. QALY's: registered direct/indirect costs, combined with EQ-5D outcome
timeFrame: Week 12 and 24
measure: Cost-effectiveness: registered direct/indirect costs combined with the primary and secondary effectiveness outcomes (Photoguide/HECSI)
timeFrame: Week 12 and 24
measure: Quality of Life: questionnaire.
timeFrame: Week 12 and 24
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: MLA Schuttelaar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: