Skoner 2011.

Methods	DESIGN: a phase III, multi‐centre, randomised, placebo‐controlled, parallel‐group, double‐blind, long‐term safety study
Participants	SYMPTOMATIC PARTICIPANTS RANDOMLY ASSIGNED: N = 92 ANALYSED: N = 66 INTERVENTION: ICS (mometasone furoate 100 μg/d): 48 CONTROL: ICS (mometasone furoate 100 μg twice daily): 44 WITHDRAWALS: reported AGE: mean (range) years INTERVENTION: ICS (mometasone furoate 100 μg/d): 6.4 (4‐9) CONTROL: ICS (mometasone furoate 100 μg twice daily): 6.3 (4‐9) GENDER: male N (%) INTERVENTION: ICS (mometasone furoate 100 μg/d): 34 (70.8) CONTROL: ICS (mometasone furoate 100 μg twice daily): 28 (63.6) ASTHMA SEVERITY: persistent asthma; severity not reported ASTHMA DURATION: mean (range) years INTERVENTION: ICS (mometasone furoate 100 μg/d): 3.8 (0.67‐8.0) CONTROL: ICS (mometasone furoate 100 μg twice daily): 4.0 (0.83‐9.0) MEAN (± SD) β2‐AGONIST USE (puffs/d): not reported DOSE OF ICS AT STUDY ENTRY AND AT RUN‐IN: washout period of 3 months ATOPY (% of participants): not reported ELIGIBILITY CRITERIA Children aged 4–9 years with a history of asthma ≥ 6 months Forced expiratory volume in 1 second (FEV1) of at least 75% of predicted normal at both the screening visit and the baseline visit, when all restricted medications had been withheld Increase in absolute FEV1 of at least 12% after reversibility testing at the screening visit or historically within the past 12 months Children 4 to 5 years old who could not demonstrate reversibility were qualified for enrolment if the investigator determined that the patient met National Heart, Lung and Blood Institute criteria for diagnosis of asthma at this age Normal height (5th–95th percentile on standard growth charts) upon measurement with a stadiometer; at least one stadiometer measurement taken between 3 and 24 months before screening Skeletal age within 2 years of chronological age (as determined by left hand‐wrist radiograph) Morning (8 am ± 1 h) plasma cortisol levels ≥ 5 μg/dL No greater than stage 1 in the Tanner Classification of Sex Maturity, as measured by preadolescent penis and testes in boys, and preadolescent pubic hair and breasts in girls; female premenarchal EXCLUSION CRITERIA Increase or decrease in FEV1 ≥ 20% between screening and baseline visits ≥ 12 puffs per day of albuterol on any 2 consecutive days between screening and baseline visits Inpatient hospitalisation for asthma control within the previous 3 months Ventilator support for respiratory failure secondary to asthma within the previous 5 years Hospital admission for the management of airway obstruction on 2 or more occasions over the past 6 months Asthma requiring daily use of nebulised SABA or any use of long‐acting β2‐agonists Asthma requiring long‐term use of inhaled or systemic corticosteroids Inability to use a DPI device or a peak flow meter History or evidence of abnormal growth Presence of any disease or condition with the potential to substantially affect growth or that required concomitant corticosteroid therapy Evidence of gross malnutrition History of any disease that could have interfered with study evaluations Individuals experiencing an upper or lower respiratory tract infection within 2 weeks of screening and baseline visits
Interventions	PROTOCOL DURATION Run‐in = 1 to 2 weeks Intervention = 52 weeks DEVICE: dry powder inhaler DOSE OF ICS INTERVENTION: mometasone furoate 100 μg/d CONTROL: mometasone furoate 100 μg twice daily CRITERIA FOR WITHDRAWAL FROM STUDY: reported
Outcomes	ANALYSIS: Analyses were done using a longitudinal random slope (LRS) model, an individual regression (IR) model and an analysis of variance (ANOVA) by extracting sources of variation due to treatment, age and gender OUTCOMES GROWTH MEASUREMENT TECHNIQUE: Growth velocity was determined from heights measured by a Harpenden stadiometer during the 52‐week treatment period PULMONARY FUNCTION TESTS: This study was not designed to evaluate efficacy measures PULMONARY FUNCTION TESTS Forced vital capacity, FEV1 and FEF25%–75% at each study visit FUNCTIONAL STATUS Occurrences of clinical asthma exacerbations: deterioration of asthma that resulted in hospitalisation, asthma symptoms requiring the addition of medication (other than SABA therapy), exacerbations requiring oral corticosteroid bursts or exacerbations requiring a significant increase in medication dosages Growth velocity, determined from heights measured by a Harpenden stadiometer during the 52‐week treatment period Growth velocity during the 3‐month follow‐up period BIOMARKERS Plasma and urine cortisol values at screening, week 26 and the final treatment visit (week 52) ADVERSE EVENTS: reported WITHDRAWALS: reported
Notes	PUBLICATION: full paper (2011) FUNDING: supported by Merck & Co, Inc CONFIRMATION OF METHODOLOGY: not received
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information on sequence generation; randomly assigned in a 1:1:1 ratio to different comparison groups
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding of participants and key study personnel ensured
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding of participants and key study personnel ensured
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data
Selective reporting (reporting bias)	Low risk	Study protocol not available but published reports include all expected outcomes, including those that were prespecified
Other bias	Low risk	Study apparently free of other sources of bias