The Rapid Eczema Trials’ Keep Control of Eczema Study: Specific advice on topical corticosteroid treatment duration for eczema flares versus usual care in adults and children. Protocol of an online, randomised controlled trial

Patient and public involvement and engagement

This trial is part of the Rapid Eczema Trials project and has been co-designed in partnership with members of the public (known as “citizen scientists”). The co-production group determined the research question, eligibility criteria, defined the intervention and comparator, selected the outcome measures and frequency of data collection, determined the trial’s duration, developed the recruitment strategy and intervention materials, and planned the process evaluation. Co-producing this trial took 7.5 months, consisting of 14 online meetings: three to prioritise the topic and 11 to design the trial. This required 6 hours of time commitment from each public member involved in prioritisation (n = 12) and 22 hours from each public member involved in trial development (n = 9). Citizen Scientists were paid for their time (£50 per 2-hour meeting). The project is co-led by a researcher (KT) and a patient with lived experience of eczema (AR).

Citizen scientists contributed to the development of study materials and tested the trial database; ensuring that processes were streamlined, and materials were inclusive and accessible. They also helped inform decisions about when and how to collect photos of the eczema during the trial, provided training to trial staff on handling follow-up phone calls, provided guidance on how to handle safeguarding concerns, helped with decisions around trial branding, advised on collecting information on current TCS-use, and are supporting efforts to boost follow-up rates and adherence to the intervention during trial delivery.

Prioritisation of the research question and development of the trial was also informed by 3 online surveys of the whole Rapid Eczema Citizen Science Community (n = 135, n = 333 and n = 136 respectively) and 2 online workshops to prioritise the topics (n = 22).

Objectives

The aim of this trial is to compare different strategies for using TCSs for the self-management of eczema over a period of 4 months in children and adults with eczema. Specifically, the study will:

Study design

This trial is a pragmatic, two-arm, parallel group, superiority randomised controlled trial, with nested process evaluation and feasibility study to test use of photographs to assess eczema signs.

Study setting

This is an online trial with no face-to-face assessments. Participants can join the study from anywhere in the UK.

Eligibility criteria

Inclusion criteria

Exclusion criteria

Interventions

This trial is an “advice trial”. Whilst both treatment strategies align with current practice and guidelines, advice varies, and people are often given conflicting or vague advice.

For the purposes of this trial, two advice strategies will be tested:

Specific advice on duration of applying TCSs (treat flare-ups for longer):

No specific advice on duration of applying TCSs (treat flare-ups as usual):

The proposed “treat flare-ups for longer” advice has been taken from the NICE Clinical Knowledge Summary (last updated May 2024),¹ which states that for flares on the body, people should be advised to continue treatment for 48 hours after the eczema has cleared. This is based on clinical opinion and without good research evidence. The advantage of doing so could be that it treats non-visible inflammation (“eczema under the skin”) and so may prolong remission; a disadvantage is that it may lead to use of more TCS than is needed.

Participants in both groups will be advised to use their usual TCS (either prescribed or bought over the counter) and will remain under the care of their usual healthcare professional. Information will also be provided to explain what an eczema flare-up is, how to apply their treatments and how to order repeat prescriptions.

Following randomisation, participants are provided with instructions as to how long they should treat their eczema flare-up for according to their group allocation. Participants are asked to follow this advice whenever they experience a flare-up during the 16-week study period. A copy of the intervention materials will be available via Figshare on completion of the trial.⁸

Outcomes

Participant reported outcomes include those recommended by the Harmonizing Outcomes for Eczema (HOME) initiative’s core outcome set validated instruments for symptoms, quality of life and eczema control. The trial is testing the feasibility of using photographs uploaded by participants to assess clinical signs (using EczemaNet artificial intelligence tool, as there are no in-person clinic visits). Itch intensity in the last 24 hours was not included to minimise responder burden in this online trial. Members of the co-design group wanted to minimise repetition and questionnaire burden in the weekly questionnaires and felt that there was little value in asking this question at baseline and end of study only.

Primary outcome

Eczema control measured by Recap of atopic eczema (Recap).⁹ Includes 7 items, scored 0 to 28. Assessed weekly over 16 weeks.

Secondary outcomes

Photographs of the eczema will be collected at week 4 and week 16 as part of the nested feasibility study.

Sample size calculation

The sample size for the trial is based on Recap scores assessed weekly for 16 weeks and is designed to detect a difference of 2.2 in Recap scores between the two groups. A small difference of 2.2 has been chosen as this trial is evaluating a simple advice strategy. In this context, even a small improvement could be important to people living with eczema and could help them to self-manage their eczema more effectively. Although 2.2 is a small change, it is likely to be beyond measurement error.¹⁴

Assuming a standard deviation in weekly Recap scores of 6.5 and a correlation between repeated measurements of 0.8 (based on data from previous eczema RCTs^15–18), a sample size of 150 per group is required to detect this difference with 90% power and 5% two-sided significance level. Randomised participants will follow their allocated treatment strategy when they have a flare-up during the trial, however some participants may join the trial and not have an eczema flare-up. Based on previous online trials,^18,19 we assume 80% of participants randomised will have at least one flare up and need to use TCS over the 16-week follow-up period. Inflating for this and allowing for 15% loss to follow-up, a total sample size of 450 is required.

Recruitment

Recruitment started on 15^th July 2025 and will continue for up to 12 months. Participants are recruited through a variety of online and offline channels, including:

Participants identified through General Practitioner (GP) practices have a recorded diagnosis of eczema on their medical records and have been issued a prescription for emollients or topical corticosteroids in the last 2 years.

Potential UK participants are guided to the trial website (https://rapideczematrials.org/keep-control-study/), where they are provided with online information about the trial. Information is provided in a variety of engaging formats appropriate for all ages.

Potential participants are encouraged to contact the trial team if they have any questions prior to registering for the trial online.

Diversity and inclusion

The INCLUDE framework²⁰ was used during trial development to explore barriers and facilitators to including people from diverse backgrounds in terms of ethnicity, skin tone, socio-economic status, language abilities, neurodiversity and geographical location. Changes made at the study design stage included: ensuring that all patient-facing materials were accessible and in varied formats (including videos); adding a question at baseline about sensory issues and use of topical treatments; informing development of the intervention materials, including signposting to prescription pre-payment certificates.

Efforts were made to encourage involvement of people from diverse cultural and socio-economic backgrounds. We are purposefully selecting GP surgeries to conduct search and mailout in areas that serve people living in areas of high deprivation, are working with ‘Deep End’ practices in Nottingham and Yorkshire to promote the trial, and are prioritising mailshots to ethnically diverse potential participants registered with Be Part of Research.

Trial procedures

Following an initial self-reported eligibility screening completed by the potential participant online, electronic consent (e-consent) is taken prior to completion of trial procedures and questionnaires. There is an optional consent section for providing photos for the feasibility study. Choosing not to provide photos does not affect participation in the main trial. For children under 16, consent is obtained from the parent/carer but there is an optional assent section for the child to complete if they wish. In addition to providing e-consent, parents/carers are asked to confirm that they have discussed participation in the trial with their child (if appropriate) and that their child is willing to take part.

If eligible for the trial and consent is provided, participants are asked to complete the following:

All assessments are carried out online through secure, bespoke weblinks to questionnaires sent via email/text. Participants receive email, text message or phone call reminders as appropriate if questionnaires have not been completed.

For children who are unable to complete patient reported outcomes themselves, proxy reporting by a parent/carer will be accepted, but, where possible, participants are encouraged to complete patient-reported outcomes in discussion with their child. Parents/carers are advised that this should be the same adult throughout the trial if possible.

Participants are invited to take photos of their/their child’s eczema and, if they choose, to upload them via a secure link to a platform hosted by Imperial College London. The uploaded photos are used to assess eczema severity using an artificial intelligence (AI) tool, called EczemaNet.²¹ Eczema severity scores and photos will be securely transferred to the Nottingham Clinical Trials Unit for assessment and archiving.

Participants who complete the final questionnaires at week 16 will be offered the opportunity to enter a free prize draw to win £20, a child-friendly book about eczema, or both, according to their preference.

Any participants who do not provide consent during the recruitment process, prior to randomisation, are not randomised, and no further data is collected.

A summary of assessments is shown in Table 1. The trial flow chart is provided in Figure 1.

Table 1. Summary of trial assessments.

	TRIAL PERIOD
	Enrolment	Baseline	Follow-up
TIMEPOINT	0	0	Month 1	Month 2	Month 3	Month 4	Weekly
ENROLMENT
Eligibility screen (including self-report of eczema diagnosis)	X
Informed e-consent (and child assent if appropriate)	X
Minimisation variables		X
Randomisation		X
INTERVENTIONS:
Treat flare-ups for longer
Treat flare-ups as usual
ASSESSMENTS:
Demographics and baseline characteristics		X
UK Diagnostic criteria		X
Prior belief in intervention		X
Eczema Control (RECAP)		X					X
Number of Days of TCS		X					X
Eczema Symptoms (POEM)		X	X	X	X	X
Changes in eczema treatments		X	X	X	X	X
Quality of Life (DLQI, CDLQI, IDQI as appropriate)		X				X
Global change in eczema compared to baseline						X
Acceptability of intervention/process outcomes						X
Flares and adherence to intervention			X	X	X	X
Adverse events –contact with healthcare professional due to worsening of eczema			X	X	X	X
Adverse events –contact with healthcare professional due to concerns about side-effects			X	X	X	X
Eczema signs from photos			X			X

Figure 1. Trial flowchart.

Participant verification

The trial database includes validation checks to prevent duplicate entries and ensure eligibility criteria are met.

To guard against imposter participants and bots joining the trial, the database uses reCAPTCHA technology to confirm human status during the screening process. Participants are not paid for contributing to the trial, to minimise incentives for people to take part solely for financial gain. The trial team also centrally monitor for sudden and unexpected spikes in recruitment, or activity at unusual times of the day.

Withdrawal procedures

Participants may withdraw their consent for follow-up and/or other trial related activities or receiving trial related communications, at any point. If participants do not contact the trial team asking to withdraw from the trial, participants will continue to receive links to the trial questionnaires and phone reminders until the end of their planned follow-up.

Randomisation

Potential participants are randomised online once consent has been provided, they have submitted their baseline information, including the outcomes specified above, and eligibility confirmed.

Randomisation, data collection and data management is provided by a secure online system at NCTU: REDCap (Research Electronic Data Capture).^22,23

Participants are randomised 1:1 to either the intervention group (advice to treat flare-ups for longer) or control group (treat flare-ups as usual) using a minimisation algorithm with a probabilistic element balancing on the following factors:

The randomised allocated group is not released to participants until after baseline variables have been entered and stored on the trial database.

Masking

As this is an advice trial, it is not possible to mask trial participants to their randomised allocation. To mitigate the potential bias caused by lack of masking, we collect prior belief in the impact of intervention strategy at baseline and explore this in a sensitivity analysis.

The trial statisticians, trial team at NCTU and members of the Trial Management Group will be masked to treatment allocation until the database is locked, prior to analysis.

Analysis

The analysis and reporting of the trial will be in accordance with CONSORT guidelines, with the primary comparative analyses being conducted according to randomised allocation regardless of adherence to allocated TCS strategy during a flare-up. The primary estimand for the trial is shown in Table 2. A statistical analysis plan will be finalised and made publicly available prior to database lock and release of the treatment allocations.

The primary analysis will use all available longitudinal outcome data and will use a linear mixed effects model to estimate the difference in mean RECAP score over the 16-week trial period with 95% confidence interval. The model will include fixed effects for the minimisation variables (age, baseline POEM score and potency of TCS) and baseline RECAP score. The following potentially prognostic variables will also be included as fixed effects if technically possible: UK Diagnostic criteria, number of days TCS used to treat last flare-up, attitudes towards use of TCS, use of TCS to prevent flares and use of topical, oral or nasal steroids (for a condition other than eczema). It will allow for observations nested within participants over time using random effects. If there is evidence of a differential effect over time, the difference in mean RECAP score each week will be reported.

Sensitivity analyses for the primary outcome will use multiple imputation for missing outcome data.

Subgroup analyses for the primary outcome will be performed according to age, potency of TCS, eczema severity, diagnosis of eczema according to UK Diagnostic Criteria, prior belief and route of recruitment (added during SAP development) by including an appropriate interaction term in the mixed effect model. The trial is not powered to detect any interactions hence the subgroup analyses will be treated as exploratory. Additional sub-group analyses may be considered as outlined in the statistical analysis plan.

Between-group comparison of secondary outcomes will use an appropriate regression model for the outcome (linear for continuous outcomes, logistic for binary) with adjustment as described above for the primary outcome and baseline outcome measure for continuous variables if available. For secondary outcomes assessed weekly or monthly, mixed effects models will be used to allow for observations nested within participants over time using random effects.

Nested process evaluation

A nested, qualitative study will consider questions of acceptability, feasibility, and adherence regarding different strategies for using TCS for the treatment of eczema flares. Data collection will also consider trial procedures, including taking and uploading photos of eczema.

Data collection will include both free-text questions in the 16-week questionnaire and more detailed qualitative interviews with a purposive sample of trial participants. Approximately 20 participants will be recruited, to capture diversity in age, gender, ethnicity, prior belief in the impact of length of flare-up treatment and acceptability of the interventions.

Only adults (aged 16+) will be included in the interviews (either as people with eczema or as parents/carers of children with eczema). Children who took part in the study may accompany their parent/carer during the interview if they wish to.

E-consent is be taken prior to the interview and consent re-affirmed verbally at the start of the interview.

Interviews will be undertaken online or by telephone, at a time convenient to the participant. Data will be digitally recorded if participants consent to this. Recordings will be transcribed and destroyed once transcripts have been approved as an accurate record. If a participant declines to be recorded, then the researcher will take notes during the conversation and these will be used for analysis purposes.

Interviews will explore the participants (i) experience with the provided treatment advice; (ii) any difficulties or challenges that they experienced in this; (iii) any difference that this made to their eczema; (iv) their willingness to continue with their allocated treatment advice; (v) their assessment of the effectiveness of the intervention and vi) their experience of taking part in the trial.

Qualitative data (both interview data and free-text questionnaire responses) will be analysed using NVivo14 software²⁴ and MS Excel respectively. Data will be analysed using framework analysis.²⁵ Themes will be described and will help to understand the trends and findings in the quantitative trial data.

Nested photo assessment feasibility study

Feasibility of using photos to assess eczema signs in future online trials will be assessed based on the number and quality of images uploaded at weeks 4 and 16; responses to the 16-week questionnaire (acceptability and barriers); and feedback provided in the process evaluation interviews.

Scores generated from photos using EczemaNet will be used to evaluate the feasibility, validity and responsiveness of eczema severity assessments based on EczemaNet assessment of clinical images. This will include summarising descriptively the proportion of participants uploading photos and whether they were of sufficient quality to generate EczemaNet scores and assessing the association between EczemaNet severity scores and patient-reported outcomes from the trial.

Trial management

Data collection

All trial data are collected via secure platforms managed by University of Nottingham, or in the case of photo uploads, by Imperial College. Trial data are collected using the REDCap platform, photo uploads using a bespoke photo upload platform and interview data using MS Office. Data collection interfaces are usable on a range of digital devices, including smartphones.

Data management and data entry

All data for the Rapid Eczema Trials will be via participant report through electronic questionnaires and stored directly into the trial database, or uploaded to the photo upload platform hosted by Imperial College. Data provided by participants in response to online questionnaires are assumed to be source data with no additional data cleaning requirements. Participants’ medical records will not be accessed.

If outcome data are collected over the phone during follow-up phone calls, or the trial team become aware of any withdrawals or protocol deviations, these will be entered into REDCap by a member of the trial team.

Programmed validation and data quality rules are used to identify data anomalies.

Checks include missing data (including missing forms), out of range values, illogical entries and invalid responses.

Further data handling details are provided in the Rapid Eczema Trials Data Management Plan, which can be found in the extended data of the online repository.⁸

Data access

The Trial Statistician, Trial Manager and Data Manager will have access to the exported datasets via a secure log-in to the database to download the datasets.

Datasets are available in REDCap in real time for a user with the appropriate permissions to download at any time.

Once all data has been locked, the final exported dataset in csv (raw) format will be subject to a quality control check to check numbers of records and fields are correct.

Oversight and monitoring

The trial is managed by Nottingham Clinical Trials Unit (NCTU). Data will be monitored by NCTU in accordance with an agreed Data Monitoring Plan.

The Trial Management Group (TMG) is responsible for overseeing the conduct and progress of the trial and consists of the CI, other co-applicants, PPI representatives, and representatives from NCTU Trial Management, Data Management, IT Programming and Statistical teams. The TMG will meet on a regular basis throughout the study and act in accordance with the Rapid TMG terms of reference.

Recruitment, retention, the proportion of participants reporting flare-ups and changes in eczema medication use during the trial will be monitored by the TMG. To maintain masking to treatment allocation, an independent statistician will produce reports to monitor adherence to the intervention advice by group allocation.

The TMG report to the Programme Management Group (PMG), who in turn report to the independent Programme Steering Committee (PSC). The PMG has oversight of the whole Rapid programme ensuring key milestones are met, and consists of the CI and co-applicants. Other researchers, staff and citizen scientists may attend PMG meetings as appropriate. The PSC provide overall supervision of the Rapid programme and advise the CI and PMG. The PSC consists of independent members, including a clinical chair, statistician, clinician and PPI members. The role and membership of the PMG and PSC are outlined in their respective charters.

Since the Rapid Eczema Trials programme includes only low-risk trials, it was agreed with the sponsor and funder that a Data Monitoring Committee was not required. The Trial Master File and evidence of audits will be made available upon request for regulatory inspections.

Confidentiality

Personal data recorded on all documents will be regarded as strictly confidential and will be handled and stored in accordance with the Data Protection Act 2018 and the UK General Data Protection Regulation (GDPR).

All participants will be assigned a unique trial number on randomisation into the trial. Names will be stored to allow personalised messages to individual participants when sending questionnaires and reminders. Details of ethnicity and other protected characteristics will be stored to enable monitoring of inclusivity.

Text messages and emails will be used to send participants reminders about trial procedures and to provide links to the required questionnaires using a unique personalised link. Participants who do not complete follow-up questionnaires will be sent text/email/phone reminders by the trial team as appropriate.

NCTU will maintain the confidentiality of all participant’s data and will not disclose information by which participants may be identified to any third party (except where this is required for trial purposes e.g. to send interventions or text reminders to participants) or organisations for which the participant has given explicit consent for data transfer (e.g. competent authority, Sponsor).

Participants wishing to receive update newsletters will be added to the trial mailing list. All participants will be sent a summary of the results that will not include personal identifiers.

Reports of qualitative data findings may include direct quotes from participants, but these will not be identifiable to individuals.

Participants will be asked not to upload images of sensitive body sites.

Ethics and consent

The study has received ethical approval by the London – Surrey Research Ethics Committee (2 Redman Place, London, E20 1JQ, United Kingdom) on 30/05/2025 (approval number: 23/PR/0899). The trial was prospectively registered before it opened to recruitment: ISRCTN29214215; 06/05/2025. This study will adhere to the Declaration of Helsinki.

ISRCTN29214215 Rapid Eczema Trials master protocol_v4.2_14Jan2026.

Protocol amendments.

This protocol summary is based on Rapid Eczema Trials master protocol_v4.2_14Jan2026.

Since the start of recruitment, the protocol was amended in September 2025 to revise the Keep Control of Eczema study–specific search criteria used by the GP Participant Identification Centres (PICs). The requirement for a TCS prescription within the previous 12 months was removed after the first seven PICs identified fewer potential participants than anticipated. This indicated that the original criterion was overly restrictive and may have excluded eligible individuals who had not received a recent prescription or because TCS were obtained over the counter. The search criteria were reverted to those specified in the master protocol, identifying individuals who had been issued a TCS prescription within the last 2 years.

In January 2026, a further protocol amendment was implemented in response to lower than anticipated follow-up questionnaire completion rates, with the aim of improving data completeness and ensuring sufficient data to address the research question. Additional details were added to the existing optional prize draw, specifying that completion of each questionnaire would result in one entry into the prize draw.

In the Trial Procedures section, flexibility in data collection methods was introduced, allowing follow-up data to be collected via alternative means (e.g. telephone) in addition to online completion.

Sponsor

The sponsor of this study is the Nottingham University Hospitals NHS Trust (nuhnt.researchsponsor@nhs.net mailto:Researchsponsor@nuh.nhs.uk).

Dissemination

This trial is part of the wider RAPID programme with a parallel knowledge mobilisation workstream aiming to accelerate meaningful uptake of new knowledge. Results of this trial will be submitted for publication in a peer-reviewed journal. Findings will be released as quickly as possible on completion of the trial, using lay-friendly formats. Trial participants and members of our Eczema Citizen Science Community will be sent a copy of the results. Summaries will be posted on the Rapid Eczema Trials website. Where relevant, findings will be incorporated into Eczema Care Online https://www.eczemacareonline.org.uk which is a NICE recommended resource²⁶ and shared widely with professional bodies and patient organisations.

Prior to release, results will be quality checked according to the NCTU statistics standard operating procedure, and interpretation of the trial results will be discussed with members of the co-design groups, the Trial Management Group and the Programme Steering Group. Since this is a citizen-science project, copies of the trial materials including the trial protocol, analysis plan, database code and analysis code will be made freely available on the Rapid Eczema Trials website for others to use. Academic journal manuscripts will be prepared by the research team and members of the coproduction groups and authorship will be determined by mutual agreement.