Condition category
Skin and Connective Tissue Diseases
Date applied
22/07/2015
Date assigned
29/07/2015
Last edited
08/08/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Hand eczema (HE) is one of the most common skin disorders and can considerably impact the daily life of sufferers. However, there is a lack of reliable evidence to direct clinical practice regarding the most effective treatment for severe HE when steroid creams are not sufficient to control the disease. In particular, there is no reliable information on the effect of treatments with patients suffering from different types of HE. This study will be the first study to directly compare Alitretinoin and immersion PUVA (two commonly available NHS treatments) to see which of these two treatments is most effective in treating which type of hand eczema. It will also examine both the short term and longer term effectiveness of each treatment in terms of both how good the hands heal with the treatment and how long the skin can remain clear once healed.

Who can participate?
Patients aged 18 or older who suffer from severe chronic hand eczema, which has not improved with strong steroid treatment for at least 4 weeks prior to participation.

What does the study involve?
A routine blood sample will be required to assess suitability for the study and to screen for atopy, which is the tendency to develop the classic allergic diseases (atopic dermatitis, allergic rhinitis [hay fever], and asthma). Participants will be randomly allocated to receive either PUVA (where the hands are exposed to ultraviolet [UV] light after they have been soaked in a solution called psoralen) or to take Alitretinoin (a tablet) over a 12-24 week period (depending on how well the hand eczema has responded). During this 12-24 week period, participants will attend clinic every 4 weeks to complete questionnaires about their hands and health, and their hands will be assessed. All participants will be asked to complete a medication diary during this period. Participants will also provide a blood sample to look at skin proteins known to be important in eczema. After this period, participants will receive standard care treatment as required. They will be asked to attend once every 4 weeks until week 36, then once every 8 weeks until week 52. At these visits, participants will complete questionnaires about their hands and health, and their hands will be assessed.

What are the possible benefits and risks of participating?
It is hoped by taking part in this study the participant will respond to treatment and have an increased quality of life. This is in line with what the participant would have experienced if treated according to normal NHS practice, as both treatments are used as standard NHS treatments. This study will help us to understand which of these treatments, if any, is more effective in the short term, and what the long-term benefits of each treatment may be. Taking part in this research study involves time and commitment such as regular hospital visits for treatment and follow-up visits. Although the number of treatment visits will be no more than if the participant receives these treatments outside of a research study setting, the follow-up visits will be in addition. The treatments used as part of the study are currently available as routine standard treatment by the NHS and therefore there are no additional risks beyond those that the participant would be exposed to as part of standard care.

Where is the study run from?
The study will be run from approximately 35-40 hospital dermatology departments across the UK.

When is the study starting and how long is it expected to run for?
The study runs from October 2015 until March 2019. Each person will take part in the study for 12 months. September 2017 is the end of the recruitment phase.

Who is funding the study?
The National Institute for Health Research (NIHR) (UK).

Who is the main contact?
Dr Victoria Goss (Senior Trial Coordinator)
ctru-alpha@leeds.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Miriam Wittmann

ORCID ID

Contact details

Chapel Allerton Hospital
LMBRU
Chapeltown Road
Leeds
LS7 4SA
United Kingdom
+44 (0)113 392 44 83
M.Wittmann@leeds.ac.uk

Type

Public

Additional contact

Dr Victoria Goss

ORCID ID

Contact details

Clinical Trials Research Unit
Leeds Institute of Clinical Trials Research
University of Leeds
Leeds
LS2 9JT
United Kingdom
+44 (0)113 343 4317
ctru-alpha@leeds.ac.uk

Additional identifiers

EudraCT number

2014-004741-27

ClinicalTrials.gov number

Protocol/serial number

DM14/11351; HTA 12/186/01

Study information

Scientific title

Comparison of Alitretinoin with PUVA as the first line treatment in patients with severe chronic hand eczema: a randomised controlled trial

Acronym

ALPHA

Study hypothesis

The aim of this study is to determine the clinical and cost effectiveness of Alitretinoin and PUVA when used in conjunction with concomitant topical corticosteroids, emollients and patient education for the treatment of severe chronic hand eczema (CHE) which is unresponsive to treatment with potent topical corticosteroids alone.

More details can be found at http://www.nets.nihr.ac.uk/projects/hta/1218601
Protocol can be found at http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0005/136994/PRO-12-186-01.pdf

Ethics approval

1. Leeds West research ethics committee, 09/01/2015, ref: 14/YH/1259
2. Amendment approved 18/03/2015

Study design

Prospective multicentre open-label two-arm parallel-group adaptive randomised controlled trial with one planned interim analysis

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Severe, chronic hand eczema

Intervention

A maximum of 780 consenting participants with severe CHE will be randomised on a 1:1 basis to receive either Alitretinoin (30 mg per day) or the phototherapy Psoralen with UV-A treatment (PUVA) (twice weekly) in conjunction with concomitant topical corticosteroids, emollients and patient education. PUVA therapy will involve photosensitising of hands by immersion in a dilute solution of Meladinine®, before exposure of hands to UV-A light.

The trial is an adaptive design with a planned interim analysis to re-estimate the sample size, which may lead to fewer than the required 780 participants, although a minimum of 500 participants will be recruited.

Intervention type

Drug

Phase

Phase IV

Drug names

1. Alitretinoin
2. Meladinine® 0.75% solution

Primary outcome measures

Disease activity of the index hand, quantified using the HECSI tool, at 12 weeks post planned start of treatment

Secondary outcome measures

1. Disease activity of the index hand, quantified using the HECSI tool, at 24 and 52 weeks post planned start of treatment
2. Disease activity of the index hand, quantified using the mTLSS tool, at 24 and 52 weeks post planned start of treatment
3. Disease activity of the index hand, quantified using the PGA tool at 24 and 52 weeks post planned start of treatment
4. Time to relapse of the index hand (HECSI score >75% baseline HECSI score of the index hand)
5. Time in remission of the index hand (defined by the period of time when patient is classed as clear/almost clear until the disease is scored as ‘mild’ or higher on the PGA scale and participants have been using topical corticosteroids daily for the previous 7 or more days)
6. Patient reported outcome using the DLQI tool, over the 52 weeks post planned start of treatment
7. Patient reported outcome using the PBI-HE over the 52 weeks post planned start of treatment
8. PeDeSi over the 52 weeks post planned start of treatment
9. Cost-effectiveness over the 52 weeks post planned start of treatment

Overall trial start date

01/01/2015

Overall trial end date

01/10/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients aged ≥18 years at the time of signing the Informed Consent Form
2. Patients suffering from uncontrolled, severe CHE defined as the presence of both of the following criteria:
2.1. PGA score of severe
2.2. Resistance to treatment with potent topical corticosteroids for ≥ 4 weeks prior to the point of eligibility screening
3. Avoidance strategies for known contact allergens are in place for at least a two-week period prior to randomisation
4. Patient has provided written informed consent
5. Patient is expected to comply with treatment and protocol schedule

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

780

Participant exclusion criteria

Skin related:
1. Patients who have a clinically suspected infection (fungal, bacterial or viral) as cause for dermatitis of the hands
2. Patients with known clinically relevant allergic contact dermatitis of the hands unless they had made a reasonable effort to avoid the contact allergen
3. Patients suffering from atopic eczema covering more than 10% of body surface (excluding hands)
4. Patients who have skin conditions worsened by the sun i.e., do not tolerate UV light (e.g., lupus erythematosus, porphyria)

Treatment related:
1. Patients who have received phototherapy/photochemotherapy in the last 3 months prior to randomisation
2. Patients who have received systemic vitamin A derivatives or other systemic immunosuppressants e.g. methotrexate or biologics treatment for HE in the last 3 months prior to randomisation
3. Patients who have received Ciclosporin A or systemic glucocorticoid steroid treatment for HE in the last 4 weeks prior to randomisation.
4. Patients receiving topical calcineurin antagonist treatment within 1 week prior to randomisation.
5. Patients receiving concomitant treatment with tetracyclines, or medication with potential for drug-drug interaction with Alitretinoin (e.g. CYP3A4 inhibitor ketoconazole) that cannot be suspended or switched to an acceptable alternative
6. Patients receiving concomitant treatment with relevant photosensitisers, when this treatment cannot be suspended for the duration of the intervention or switched to an acceptable alternative
7. Patients with a history of melanoma skin cancer, or patients with a history of non-melanoma skin cancer depending on history, location and “severity” of the non-melanoma skin cancer based on experience from routine practice
8. Patients who have received prior treatment with arsenic agents or ionising radiation in the treatment area (e.g. hands)

General:
1. Women who are lactating or of child bearing potential (WCBP, Appendix 1) with:
1.1. Positive pregnancy test (absence of pregnancy will be confirmed with a negative pregnancy test before randomisation)
1.2. Unwilling to follow pregnancy prevention program measures* (see below) whilst receiving treatment and after the last dose of protocol treatment as indicated in the relevant SmPC
2. Patients with hepatic insufficiency (alanine aminotransferase and/or aspartate aminotransferase > 2.5 times the upper limit of normal), known severe renal insufficiency, uncontrolled hyperlipidaemia (for all of the following: triglycerides, cholesterol and/or LDL cholesterol) or uncontrolled hypothyroidism in the 12 week period prior to randomisation
3. Patients with known hypersensitivity to peanut, soya or vitamin A derivatives or with rare hereditary fructose intolerance as determined by patient history
4. Patients currently suffering from hypervitaminose A as directed by clinical symptoms or patient history
5. Patients previously participated in the ALPHA trial

*Rigorous contraception for women of childbearing potential is required 1 month before treatment, during the treatment period and 1 month after cessation of treatment as per usual standard practice.

Recruitment start date

01/10/2015

Recruitment end date

30/09/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Leeds Teaching Hospital NHS Trust
Musculo Skeletal office, 2nd floor Chapel Allerton Hospital Chapeltown road
Leeds
LS7 4SA
United Kingdom

Trial participating centre

35-40 hospital dermatology departments
-
United Kingdom

Sponsor information

Organisation

Unversity of Leeds (UK)

Sponsor details

Faculty Head of Research Support
Faculty of Medicine and Health Research Office
Level 10
Room 10.110
Worsley Building
University of Leeds
Clarendon Way
Leeds
LS2 9NL
United Kingdom

Sponsor type

University/education

Website

http://www.leeds.ac.uk

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

01/10/2019

Participant level data

Stored in repository

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes