About PEARLS Overview Meet our team Contact us Information for Participants

PEARLS Trial

Proactive against reactive therapy for the prevention of lichen sclerosus exacerbation and progression of disease – a pragmatic, parallel group randomised controlled trial with embedded economic evaluation and process evaluation

Abbreviations: LS – Lichen Sclerosus; TCS – Topical Corticosteroid; SCC - Squamous Cell Carcinoma; PIC - Participant Identification Centre

About PEARLS

Vulval Lichen Sclerosus (LS) is a chronic inflammatory condition, with incidence peaking in childhood and post-menopause. Reported prevalence is up to 3%, affecting around 1 million women in the UK. Inflammation causes whitening of vulval tissue, bleeding under the skin, texture change and cuts. Patients report itching, pain (particularly during sex) and discomfort in daily activities. Untreated LS can cause progressive loss of vulval architecture. Scarring may occur early in the disease and is irreversible without surgery. LS persisting beyond puberty may prevent normal vulval anatomical development.

LS is associated with risk of vulval intraepithelial neoplasia and vulval Squamous Cell Cancer. Rates of vulval SCC with LS are 20 times higher than in the general population with higher mortality than vulval SCC without LS.

The impact of LS is considerable due to the intimate and ‘taboo’ nature of the problem. LS affects psycho-social and sexual functioning and leads to embarrassment, isolation and relationship breakdown/difficulty in forming new relationships.

Who is organising and funding this study?

The trial is being organised by the University of Nottingham (the Sponsor) and coordinated centrally by the Nottingham Clinical Trials Unit (NCTU).

This study is funded by National Institute for Health and Care Research (NIHR) Heath Technology Assessment (HTA) Ref: NIHR135121.

Chief Investigator: Dr Rosalind Simpson, Associate Professor and Consultant Dermatologist

Link to PEARLS NIHR Research Award

NIHR-White-Background NCTU-white-background

Overview

We are conducting a 2-arm, parallel-group, individually randomised, unblinded, multicentre, superiority trial with an internal pilot phase.

The trial aims to recruit 400 female participants (aged 5 years and older) over a 12 month period. Each participant will be followed up for 24 months.

The trial will compare a topical corticosteroid (TCS) applied on two non-consecutive days per week, even in absence of symptoms, (‘proactive treatment’) versus TCS as required to use only to treat a flare until symptoms resolve (‘reactive treatment’), for 12 months. The treatments will not be blinded. Choice of potent/superpotent TCS preparation is tailored to the patient as not all patients can tolerate a specific formulation.

Trial Intervention

Intervention: Potent or superpotent Topical Corticosteroid (TCS) used for two non-consecutive days per week even in absence of symptoms (‘proactive treatment’).

Comparator: treatmeant of flare as required with potent or superpotent TCS, i.e. ‘reactive treatment’, daily until flare resolves (typically up to 7 days).

Trial sites

The trial participants will be recruited from approximately 15 UK sites. Participant Identification Centres (PICs) will be set up at GP practices where potential participants will be identified with pre-defined eligibility criteria. Patients will be then referred to nearby trial sites (secondary care centres), i.e. hospitals or local gynaecology hubs.

Trial outcomes

Primary outcome

Number of flares over 12 months. Flare is defined as worsening of simptoms requiring increased application of TCSs.

Secondary outcomes

For the purposes of recording outcomes, age categories are divided into:

Children (5 - <12 years)
Adolescents (12 - <16 years)
Adults (16 years and over)

Clinical effectiveness

Progression of scarring assessed by blinded assessor at 12 and 24 months by comparing post randomisation to baseline photographs (if participant consented), or assessed clinically if consent has not been given for photographs:
- Adults: scarring worsened (yes/no)
- Children and adolescents: failure of normal vulval development (clinical assessment) and/or evidence of scarring (yes/no).
Vulvar Architectural Severity Scale at 12 and 24 months post randomisation (VASS).
Time to first flare.
Global clinical severity assessment of LS (5-point ordinal scale) at 3, 6, 12, 18 & 24 months, plus assessed by blinded assessor at 12 and 24 months.
Condition specific QoL at 3, 6, 12, 18 & 24 months using:
Vulvar Quality Life Index (VQLI) (adults)
Children’s Dermatology Life Quality Index (CDLQI) (adolescents and children).
Sexual function (adults only) using Female Sexual Function Index at 12 & 24 Months.

Safety

Development of vulval intraepithelial neoplasia or vulval squamous cell carcinoma at 24 months.
Targeted adverse events e.g. stinging, skin thinning measured by patient reported symptoms and clinical examination from randomisation over 24 months.

Treatment acceptability and potential barriers/facilitators to treatment

Acceptability of treatment strategy at 12 and 24 months using a Likert scale.
Adherence to treatment at 3, 6, 12, 18 & 24 months.
Qualitative interview sub-study at 12 months.

Cost-effectiveness

Generic utility instrument to measure QoL at 3, 6, 12, 18 & 24 months with EQ-5D-5L (adolescents and adults) and CHU-9 (children).
Resource use including prescription, direct and indirect healthcare and out-of-pocket costs associated with LS at 3, 6, 12, 18 and 24 months.

Meet our team of researchers

Chief Investigator

Rosalind is a consultant dermatologist at Nottingham University Hospitals and Associate Professor at the Centre of Evidence Based Dermatology. She is a general dermatologist with specific clinical and academic interests in women’s health and vulval dermatology. She is funded by an NIHR Advanced Fellowship and current projects revolve around the accurate diagnosis, long-term treatment, and core outcomes in lichen sclerosus. She is research lead for the BSSVD, associate section editor at the British Journal of Dermatology and co-editor for the next edition of Rook’s Textbook of Dermatology.

Research Team

Prof Kim Thomas	Co-director, centre of evidence-based dermatology
Prof Jane Daniels	Co-director of NCTU
Dr Reuben Ogollah	Associate Professor of Medical Statistics and Clinical trials
Prof Tracey Sach	Professor of Health Economics
Dr Sarah Hillman	Clinical Lecturer, GP
Dr Simi Sudhakaran	GP Partner and speciality Doctor (Dermatology)
Dr Sophie Rees	Co-applicant/Senior Research Fellow
Dr Tess McPherson	Consultant Paediatric Dermatologist
Dr Vanitha Sivalingam	NIHR Academic Clinical Lecturer in Gynaecological Oncology, Division of Cancer Sciences
Claire Baumhauer	Parent Representative
Emma Norman	Parent Representative

Trial Team

NCTU-white-background

Trial Management Team

Hugh Jarrett - Senior Trial Manager

Tina Griffin - Trial Manager

Becca Ward - Trial Co-ordinator

Database Team

Hollie Chappell - Data Coordinator

Lisa Evans - Data Manager

Shelby Castle - Database Systems Developer

Email: PEARLS@nottingham.ac.uk

Information for Participants

What is the study about?

Lichen sclerosus (LS) is an itchy and distressing condition affecting vulval skin (the skin around the outside of the vagina). It can lead to scarring if it is not treated. Scarring can cause the labia minora (inner lips) to fuse together or the entrance to the vagina to narrow. LS affects around 1 million women in the UK. People with LS are at higher risk of developing vulval cancer. Vulval LS can affect children and women of any age, but it is more common in women who have gone through the menopause and children before puberty. It is a long-term condition that needs ongoing treatment to manage flares of symptoms. LS flares are usually treated with steroid creams to get control of the symptoms.

What are we trying to find out?

We do not know the best way to manage future flares of LS. Some people think that using steroid cream inbetween flares, even when there are no symptoms, may reduce symptoms overall. We want to study if using a steroid treatment regularly (e.g. twice a week), even when symptoms are controlled, is better than using steroid cream only during a flare.

This study will enrol 400 women and randomly allocate half to use their steroid cream twice a week, and half to only use it if they experience symptoms (i.e. a flare). We will compare how many people in each group experience a LS flare. We will use photographs taken at the start to see if scarring has worsened during the study. Any patient aged 5 and over with vulval LS will be able to enter the study, regardless of ethnicity or background. We will follow patients for two years to gather data to answer our questions. We will also ask for permission from patients to check their medical records for a number of years after the study. This will help us to see how many patients in each treatment group get cancer. We will interview patients to explore how they feel about the study and the different ways of treating LS that we are testing. We will also compare the costs and outcomes of the two treatments used in the study to see if one is better value for money for the NHS.

Why are we doing this?

It is important to understand the best way to treat LS to reduce the long-term impact of the condition. If one treatment is better, patients in the future can be advised how best to manage their condition. Avoiding flares of LS and reducing scarring will improve the quality of life of patients and reduce need for treatments and support.

How will we involve patients and the public?

Two patient representatives are part of the study team. They are both women with LS. They have been involved in designing the study. We conducted an online survey involving 393 people with LS to inform the design of our study. Our patient representatives will continue to advise on the study as it progresses. We have also formed an advisory panel of women with LS and parents of girls with LS. This panel was consulted during the development process and will continue to contribute during the course of the study.

How will the results of the trial be shared?

The results of this study will be used to write clinical guidelines that doctors and pat ients will use to make decisions about their treatment. Everyone who takes part in the study will be sent the study results. We will also share them with patients via patient groups and social media, such as the UK LS support group on Facebook. The results will be written up in academic journals and shared at conferences.

Contact us

If you have any queries, please contact the PEARLS trial team.

Email: PEARLS@nottingham.ac.uk

Address: Nottingham Clinical Trials Unit, Applied Health Research Building, University Park, The University of Nottingham, Nottingham, NG7 2RD

Important links:

http://www.ukdctn.org/news/pearls-study-funded-by-nihr.aspx

Follow us on:

@PEARLS_Trial

@PEARLS_Nottingham

@PEARLS_Trial_Nottingham