Systemic therapy for vulval erosive lichen planus
| ISRCTN | ISRCTN81883379 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN81883379 |
| EudraCT/CTIS number | 2014-000547-32 |
| Secondary identifying numbers | 16788 |
- Submission date
- 12/06/2014
- Registration date
- 12/06/2014
- Last edited
- 08/11/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Skin and Connective Tissue Diseases
Plain English Summary
Background and study aims
Erosive lichen planus affecting the vulval area causes painful ulcers which last for a long time and are difficult to treat. Very little research has taken place into treatments for erosive lichen planus affecting the female external genital area (vulva) and it is not clear which is the best treatment for people who have severe disease. To find that out, this study compares three most commonly used tablets against an ointment and a short course of steroid tablets. The tablets fine tune or dampen the body's immune system. This is because an overactive immune system is thought to be the cause of erosive lichen planus.
Who can participate?
Adult patients with vulval erosive lichen planus that has not responded well to standard treatment with creams and ointments.
What does the study involve?
Participants are randomly allocated to take one of the four treatments, although some of the treatments require additional tablets to be taken alongside them to prevent side effects. Participants are able to use a moisturising cream and strong steroid ointment alongside the tablet treatment. They are given the treatment for 6 months at first, after which time it can be continued if it has been effective. If it has not been effective, treatment can be changed. This is a decision that is made between the participant and their hospital consultant.
What are the possible benefits and risks of participating?
There are no guaranteed direct benefits because it is not known for sure that the medications help but the information from this study may help to guide doctors in how patients should be treated in the future. Because this study is comparing four commonly used treatments and the study is designed to mimic normal care, there are no additional risks to participants in taking part in this study. The care that participants receive is very similar to the care that they would receive if they were not taking part in the study. Participants are closely monitored as part of their usual care.
Where is the study run from?
The study is run from certain hospital departments in the UK that specialize in treating vulval skin disorders.
When is the study starting and how long is it expected to run for?
June 2014 to April 2016
Who is funding the study?
The National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Dr Rosalind Simpson
helpstudy@nottingham.ac.uk
Contact information
Scientific
Centre of Evidence Based Dermatology
Kings Meadow Campus
Lenton Lane
Nottingham
NG7 2NR
United Kingdom
| rosalind.simpson@nottingham.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Not specified |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | http://www.nottingham.ac.uk/research/groups/cebd/documents/researchdocs/help-pis-final-v2-0-31-03-14.pdf |
| Scientific title | A randomised controlled trial of adjunctive systemic therapy for vulval Erosive Lichen Planus |
| Study acronym | hELP |
| Study hypothesis | To test whether hydroxychloroquine, methotrexate or mycophenolate mofetil are better than standard care with topical clobetasol propionate 0.05% plus a short course of oral prednisolone in patients with vulval erosive lichen planus that has been refractory to first-line therapy. |
| Ethics approval(s) | NRES Committee Yorkshire and The Humber - Sheffield, 14/04/2014, ref: 14/YH/0046 |
| Condition | Topic: Dermatology; Subtopic: Skin (all Subtopics); Disease: Dermatology |
| Intervention | Participants will be randomised to receive one of the three active interventions or to receive the comparator, clobetasol propionate 0.05% plus oral prednisolone, which is standard care: 1. Hydroxychloroquine, oral administration, up to 6.5 mg/kg lean body weight, maximum dose of 200 mg BD (in conjunction with topical clobetasol propionate 0.05%). Treatment duration 6 months. 2. Methotrexate, oral administration, dose commencing at 5 mg/week and gradually increase as per protocol according to response to a maximum of 25 mg/week (in conjunction with topical clobetasol propionate 0.05%. Treatment duration 6 months. 3. Mycophenolate mofetil, oral administration, dose commence at 500 mg OD and gradually increase as per protocol according to response to a maximum dose of 1.5 g BD (in conjunction with topical clobetasol propionate 0.05%) Treatment duration 6 months. 4. Standard care: Clobetasol propionate 0.05% (standard care), topical application, once daily for 1 month and regimen reduced according to response. Maximum 60 g over 6 months (British Association of Dermatologists guidance for the treatment of lichen sclerosus). Oral prednisolone: an initial 4-week course on a reducing regimen of 20 mg OD for 1 week, reducing by 5 mg per week. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Hydroxychloroquine, methotrexate, mycophenolate mofetil, clobetasol propionate, prednisolone |
| Primary outcome measure | Current primary outcome measures as of 08/12/2014: Proportion of participants achieving treatment success at 6 months; Treatment should be classed as successful if both criteria and are met: 1. Patient Global Assessment score of 0 or 1 on a 4-point scale 2. Assessment of improvement from baseline judged by clinical images Previous primary outcome measures: Proportion of participants achieving treatment success at 6 months; Treatment should be classed as successful if both criteria and are met: 1. Patient Global Assessment score of 0 or 1 on a 4-point scale 2. Investigator Global Assessment of improvement from baseline judged by clinical images |
| Secondary outcome measures | Current secondary outcome measures as of 08/12/2014: 1. Reduction in pain/soreness 2. Global assessment of disease assessed through: 2.1. Patient Global Assessment 2.2. Investigator Global Assessment by treating clinician 2.3. Assessment by blinded assessor using clinical images 3. Assessment of other affected mucosal sites by treating clinician 4. Psychological assessment using the Hospital Anxiety and Depression Scale 5. Assessment of sexual function 6. Health-related quality of life – using: 6.1. Skindex-29 6.2. Short Form 36 7. Days of topical steroid use during treatment period 8. Treatment satisfaction – assessed as overall satisfaction plus number of participants continuing treatment post the primary endpoint 9. Adverse events (AEs) reported during the study, and discontinuation of medications due to AEs 10. Average cost of intervention in each treatment group per participant Previous secondary outcome measures: 1. Reduction in pain/soreness 2. Global assessment of disease assessed through: 2.1. Patient Global Assessment 2.2. Investigator Global Assessment by treating clinician 2.3. Investigator Global Assessment by blinded assessor using clinical images 3. Assessment of other affected mucosal sites by treating clinician 4. Psychological assessment using the Hospital Anxiety and Depression Scale 5. Assessment of sexual function 6. Health-related quality of life –using 6.1. Skindex-29 6.2. Short Form 36 7. Days of topical steroid use during treatment period 8. Treatment satisfaction – assessed as overall satisfaction plus number of participants continuing treatment post the primary endpoint 9. Adverse events (AEs) reported during the study, and discontinuation of medications due to AEs 10. Average cost of intervention in each treatment group per participant |
| Overall study start date | 01/06/2014 |
| Overall study end date | 30/04/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 96; UK Sample Size: 96 |
| Participant inclusion criteria | Current inclusion criteria as of 08/12/2014: 1. Clinical diagnosis of erosive lichen planus affecting the vulvovaginal region (ELPV) 2. Documented histological examination in the patient’s history that excludes malignant/pre-malignant disease. Biopsy should be repeated if clinically indicated prior to consideration of systemic therapy 3. Inadequate disease control despite first-line therapy with clobetasol propionate 0.05% for at least 3 months 4. Moderate or severe disease on Investigator Global Assessment 5. Microbiological swabs negative, or result that is not clinically relevant, at study entry 6. Willing and capable of giving informed consent 7. Willing to have clinical images taken 8. Female aged 18 years or over 9. Use of effective contraceptive methods in females of childbearing age for the duration of treatment 10. For participants receiving methotrexate to use effective contraceptive methods until 6 months after the end of treatment Previous inclusion criteria: 1. Clinical diagnosis of erosive lichen planus affecting the vulva 2. Histological examination within the past 12 months to exclude alternative diagnoses 3. Inadequate control despite first-line therapy with clobetasol propionate 0.05% 4. Disease severity of moderate-severe on Investigator Global Assessment 5. Negative microbiological swabs at study entry 6. Willing and capable of giving informed consent 7. Willing to have clinical images taken 8. Age >18 years (there is no upper age limit) 9. Use of effective contraceptive methods in females of childbearing age Target Gender: Female; Upper Age Limit 99 years ; Lower Age Limit 18 years |
| Participant exclusion criteria | Current exclusion criteria as of 08/12/2014: 1. Cases of lichen sclerosus/lichen planus overlap 2. Received one or more of the trial drugs within the last one month (excluding clobetasol propionate 0.05%) 3. Previous/current diagnosis of malignant disease (skin or internal) 4. History of or current diagnosis of pre-malignant vulval skin or cervical disease 5. Receiving concurrent medications that would preclude the use of any of the trial medications in normal practice 6. History of clinically significant renal or liver impairment or other pre-existing medical conditions that would preclude the use of any of the trial medications in normal practice 7. Administration of a live vaccine (BCG, Measles, Mumps, Rubella, Yellow Fever, Oral Polio, Oral Typhoid) within the last 2 weeks 8. Pregnancy or breast-feeding 9. Known allergy to any of the trial medications Previous exclusion criteria: 1. Cases of lichen sclerosus/lichen planus overlap 2. Patients taking beta blockers or non-steroidal anti-inflammatory medications 3. Received one or more of the trial drugs within the last month (excluding clobetasol propionate 0.05%) 4. Previous/current diagnosis of malignant disease (skin or internal) 5. Pre-malignant vulval skin or cervical disease 6. Receiving concurrent medications that would preclude the use of any of the trial medications in normal practice 7. History of clinically significant renal or liver impairment or other pre-existing medical conditions that would preclude the use of any of the trial medications in normal practice 8. Administration of a live vaccine (BCG, measles, mumps, rubella, yellow fever, oral polio, oral typhoid) within the last 2 weeks 9. Pregnancy or breastfeeding 10. Known sensitivity to any of the trial medications |
| Recruitment start date | 15/08/2014 |
| Recruitment end date | 31/07/2015 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Nottingham
NG5 1PB
United Kingdom
Aberdeen
AB25 7ZD
United Kingdom
Blackburn
BB2 3HH
United Kingdom
Bradford
BD5 0NA
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Leeds
LS7 4SA
United Kingdom
Liverpool
L14 3LB
United Kingdom
London
E11 1NR
United Kingdom
Manchester
M13 9WL
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
DD1 9SY
United Kingdom
Salford
M6 8HD
United Kingdom
Sponsor information
University/education
Division of Primary Care
Graduate Medical School
London
NG7 2NR
England
United Kingdom
"ROR" |
https://ror.org/01ee9ar58 |
|---|
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 01/09/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Intention to publish approx September 2017 in a peer reviewed journal. Dissemination to take place by presentation at appropriate multidisciplinary conferences. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Kim Thomas (kim.thomas@nottingham.ac.uk). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 04/01/2016 | Yes | No | |
| Basic results | 10/03/2017 | 28/06/2017 | No | No | |
| Results article | results | 01/10/2018 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- ISRCTN81883379_BasicResults_10Mar17.pdf
- Uploaded 28/06/2017
Editorial Notes
08/11/2018: Publication reference added.
28/06/2017: The basic results of this trial have been uploaded as an additional file.
27/06/2017: IPD sharing statement added.
08/12/2014: The outcome measures and inclusion/exclusion criteria were updated and the recruitment dates were added.
