Alitretinoin vs Azathioprine in Severe Non-hyperkeratotic Hand Eczema (ALIAZ)

May 1, 2018 updated by: Marie-Louise A Schuttelaar, MD, PhD, University Medical Center Groningen

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

116

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Alitretinoin
Patients with severe chronic non-hyperkeratotic hand eczema, randomized to treatment with alitretinoin.
Drug: Alitretinoin
Oral alitretinoin capsule of 30mg once daily for a total of 24 weeks.
Other Names:
  • Toctino
  • 9-cis-retinoic acid
  • ATC code: D11AH04
Active Comparator: Azathioprine
Patients with severe chronic non-hyperkeratotic hand eczema, randomized to treatment with azathioprine.
Drug: Azathioprine
Oral azathioprine tablets twice daily in a dose of 1.5 or 2.5mg/kg/day, depending on the thiopurine methyltransferase (TPMT) activity.
Other Names:
  • Imuran
  • Azafalk
  • ATC code: L04AX01

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Response to treatment/hand eczema severity (Photoguide)
Time Frame: 24 weeks (end of treatment)
24 weeks (end of treatment)

Secondary Outcome Measures

Outcome Measure
Time Frame
Response to treatment/hand eczema severity (Photoguide)
Time Frame: 12 weeks
12 weeks
Response to treatment/hand eczema severity (Hand Eczema Severity Index, HECSI)
Time Frame: Week 4, 8, 12, 24
Week 4, 8, 12, 24
Time to response
Time Frame: Week 4, 8, 12, 24
Week 4, 8, 12, 24
Patient reported improvement (Patient Global Assessment, PaGA)
Time Frame: Week 12 and 24
Week 12 and 24
Safety and tolerability (adverse events)
Time Frame: Up to 24 weeks
Up to 24 weeks
Cost-utility. QALY's: registered direct/indirect costs, combined with EQ-5D outcome
Time Frame: Week 12 and 24
Week 12 and 24
Cost-effectiveness: registered direct/indirect costs combined with the primary and secondary effectiveness outcomes (Photoguide/HECSI)
Time Frame: Week 12 and 24
Week 12 and 24
Quality of Life: questionnaire.
Time Frame: Week 12 and 24
Week 12 and 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Investigators

  • Principal Investigator: MLA Schuttelaar, MD, PhD, University Medical Center Groningen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2016

Primary Completion (Anticipated)

December 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

August 18, 2016

First Submitted That Met QC Criteria

January 18, 2017

First Posted (Estimate)

January 20, 2017

Study Record Updates

Last Update Posted (Actual)

May 4, 2018

Last Update Submitted That Met QC Criteria

May 1, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 52232

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Data will be published anonymously and will not be possible to trace back to individual participants.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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