Wolthers Ole D, Stone Sally, Bareille Philippe, Tomkins Susan, Khindri Sanjeev
Asthma and Allergy Clinic, Children´s Clinic Randers, Denmark.
Clinical Development, Respiratory Therapy Area Unit, GlaxoSmithKline, Uxbridge, UK.
Clin Ther. 2017 Jun;39(6):1191-1199. doi: 10.1016/j.clinthera.2017.04.011. Epub 2017 May 22.
A dry powder inhaler formulation of the inhaled corticosteroid fluticasone furoate (FF) is being evaluated for use in children. An important potential risk associated with the use of inhaled corticosteroids in children is growth suppression. Therefore, the aim of this study was to assess the short-term lower leg growth in children with asthma treated for 2 weeks with inhaled FF versus placebo from the ELLIPTA inhaler.
Prepubertal children with persistent asthma (n = 60; aged 5 to <12 years) were recruited into a randomized, double-blind, placebo-controlled, 2-way crossover, noninferiority study. The study consisted of four 2-week periods: run-in, 2 treatment periods, 1 washout period, and a 1-week follow-up period. Interventions were FF 50 µg and placebo once daily in the evening. Lower leg length was measured by using knemometry.
The randomized ITT population comprised 36 boys and 24 girls with a mean age of 8.7 (standard deviation, 1.5; range, 5-11) years; 58% had a duration of asthma ≥5 years. Fifty-eight subjects completed both treatment periods. The least squares mean growth rate was 0.31 mm/week during treatment with FF and 0.36 mm/week during the placebo period. The difference in adjusted least squares mean growth rates between FF and placebo was -0.052 mm/week with a 95% CI of -0.122 to 0.018. This finding was greater than the prespecified noninferiority margin of -0.20 mm/week. The overall incidence of adverse events was 35% with placebo and 22% with FF.
Inhaled FF 50 µg provided once daily for 2 weeks was noninferior to placebo in terms of effects on short-term lower leg growth in children with asthma. To further quantify the risk of growth suppression in children, intermediate-term growth studies should be conducted. Inhaled FF 50 µg was well tolerated in this study population. ClinicalTrials.gov identifier: NCT02502734.
正在评估吸入性皮质类固醇糠酸氟替卡松（FF）的干粉吸入剂配方用于儿童的情况。在儿童中使用吸入性皮质类固醇的一个重要潜在风险是生长抑制。因此，本研究的目的是评估使用ELLIPTA吸入器吸入FF与安慰剂治疗2周的哮喘儿童的短期小腿生长情况。
招募青春期前持续性哮喘儿童（n = 60；年龄5至<12岁）进入一项随机、双盲、安慰剂对照、双向交叉、非劣效性研究。该研究包括四个2周周期：导入期、2个治疗期、1个洗脱期和1周随访期。干预措施为每晚一次FF 50μg和安慰剂。使用小腿测量法测量小腿长度。
随机意向性分析人群包括36名男孩和24名女孩，平均年龄8.7（标准差1.5；范围5 - 11）岁；58%的哮喘病程≥5年。58名受试者完成了两个治疗期。FF治疗期间的最小二乘平均生长速率为0.31毫米/周，安慰剂期为0.36毫米/周。FF与安慰剂之间调整后的最小二乘平均生长速率差异为 -0.052毫米/周，95%置信区间为 -0.122至0.018。这一结果大于预先设定的非劣效性界值 -0.20毫米/周。安慰剂组不良事件总发生率为35%，FF组为22%。
每日一次给予50μg吸入性FF治疗2周，在对哮喘儿童短期小腿生长的影响方面不劣于安慰剂。为进一步量化儿童生长抑制风险，应进行中期生长研究。本研究人群对50μg吸入性FF耐受性良好。ClinicalTrials.gov标识符：NCT02502734。
