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 across the UK.  The trial plans to open 15 recruiting centres (sites).  Click on a pin on the map for details of selected trial sites.

Participant Identification Centres (PICs) will be set up at GP practices where potential participants will be identified with pre-defined eligibility criteria. Initially only PICs sites that are in the proximity of two sites, Nottingham University Hospital and Liverpool Womens' Hospital, will be in operation.  Patients will also be able to self-refer to these two sites.

Recruitment update

 Inclusion & exclusion criteria 

Inclusion criteria

1. Clinical or biopsy confirmed diagnosis of vulval LS

2. Currently controlled disease (asymptomatic with minimal clinical evidence of active disease) at baseline

3. Age ≥5 years

4. Able to give consent/child assent plus parental consent

Exclusion criteria

1. Previous vulval intraepithelial neoplasia (VIN) or vulval squamous cell carcinoma (SCC)

2. Contraindications to topical steroids

3. Concomitant use of other topical anti-inflammatory vulval treatments

4.Using systemic immunosuppressants (for any indication)

5. Using systemic treatment for LS

6. Patients with surgical alteration of vulval skin as part of gender reaffirming surgery, or patients not born with a vulva

7. Pregnant and breastfeeding women 

Trial outcomes

Primary outcome

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

Secondary outcomes

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

1. Children (5 - <12 years)

2. Adolescents (12 - <16 years)

3. 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:Vulvar Architectural Severity Scale at 12 and 24 months post randomisation (VASS).

  • Adults: scarring worsened (yes/no)
  • Children and adolescents: failure of normal vulval development (clinical assessment) and/or evidence of scarring (yes/no).

• 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.