Kirkup 2003b.

Study characteristics
Methods	Trial design: randomised, double‐blind, multicentre, parallel study Trial registration number: not reported Country: 14 centres in 7 countries in Europe and South Africa (assumed from acknowledgements) Outpatient or hospital: clinic attendance Date trial conducted: not reported Duration of trial participation: up to 18 weeks (1 to 2 week run‐in phase, 2 to 4 week acute phase, 3‐month maintenance phase, follow‐up 2 weeks post‐trial) Inclusion criteria: · Children aged 2 to 14 years · Participants experiencing a flare of moderate‐severe AD with a total AD score of ≥ 6 (see outcomes for definition) Exclusion criteria: · Signs of skin infection or the dermatitis was severe enough to warrant hospital admission · Use of potent or very potent TCS · Systemic treatment for skin disease during the previous 3 weeks · Oral or parenteral corticosteroids within the previous 12 months · History of adverse response to corticosteroids · Concomitant serious or unstable disease · Participation in another clinical trial within the previous 4 weeks Additional design details: participants were randomised once at the end of the run‐in period. The randomised part of these trials was also in 2 treatment phases, acute phase (twice daily TCS) and then maintenance (TCS applied at first sign of the flare).
Participants	Total number randomised: 128 participants (66 to apply the intervention group and 62 to apply the comparator group) Age: overall mean 8 years (SD 3) Sex: intervention group, female n = 26, male n = 40; comparator group, female n = 33, male = 29 Ethnicity: not reported Duration of eczema: intervention group, median 4 years, range 0 to 14 years; comparator group, median 6 years, range 0 to 14 years Severity of eczema: baseline mean total AD score (see outcomes for definition of 0‐21 scale): intervention group: 10.71 (n = 59); comparator group: 12.11 (n = 54) Body site: intervention group, hands and wrists 18%, front of arms 30%, back of legs 14%, feet and ankles 5%, neck and shoulders 12%, front of legs 6%, back of arms 3%, other 12%; comparator group, hands and wrists 21%, front of arms 19%, back of legs 23% Number of withdrawals: n = 18: intervention group n = 7, comparator group n =11 due to (some participants provided > 1 reason) treatment failure (comparator n = 5); non‐compliance or personal reasons (intervention n = 2, comparator n = 3), AE (intervention n = 1, comparator n = 3), protocol violation (comparator n = 2), not specified (intervention n = 4, comparator n = 4) Notes: none
Interventions	Run‐in details: all participants initially applied hydrocortisone 1% cream twice daily to affected areas for 1 to 2 weeks. Intervention: fluticasone propionate 0.05% cream used twice daily for 14 to 28 days until the investigator judged their eczema was stabilised. Participants then entered a 3‐month maintenance phase and applied the trial treatment "as required" (up to twice daily) to affected areas at the first sign of a relapse. Concurrent treatment: not reported Other key information: none Comparator: hydrocortisone butyrate 0.1% cream used twice daily for 14 to 28 days until the investigator judged their eczema was stabilised. Participants then entered a 3‐month maintenance phase and applied the trial treatment "as required" (up to twice daily) to affected areas at the first sign of a relapse. Concurrent treatment: not reported Other key information: none Concurrent treatments received alongside both intervention and comparator: investigators were permitted to issue tubes of hydrocortisone 1% cream for the face (labelled "face treatment") and emollients, as required. Regular inhaled and intranasal corticosteroids were permitted. Notes: none
Outcomes	· Total AD score: (maximum 21) = number of body areas affected (out of a possible 12 body areas) + sum of scores for target area (maximum 9 as erythema, excoriation and lichenification were each graded 0‐3) · Physician‐reported "overall assessment of treatment success" grouped ‘much improved/improved’ or ‘same/worse/much worse’ · Daytime itch recorded through participant diaries · Sleep disturbance through participant diaries · AE · Routine urinalysis, biochemical and haematological screening at enrolment and end of the maintenance phase · Weight of used and unused trial cream tubes at end of 3‐month maintenance phase · Intensity of rash recorded in participant diaries. For the diary card data, mean values over the last 7 days before the end of the acute treatment phase were used in the analysis. · Usage of antipruritic or sedative drugs during the maintenance phase · Median time to recurrence of AD. Recurrence defined as an increase of 1.0 in either the number of body areas affected or, in the sum of scores (for erythema, excoriation and lichenification) for the target area. Time to recurrence of AD was calculated from the visit dates for those participants who had a recurrence during the maintenance phase.
Notes	Funding source: Glaxo Wellcome R & D, UK (FLT411/412) Declarations of interest: not declared Original language of publication: English Other: this study has previously been extracted by this group; some content is reproduced from Lax 2022.