哮喘儿童每天一次维兰特罗加吸入糖皮质激素治疗的随机试验
2016/06/20
摘要
背景:吸入糖皮质激素（ICS）对儿童哮喘的维持治疗是有效的，然而，许多孩子仍然得不到控制。维兰特罗（VI）是一种吸入长效β-2受体激动剂，与ICS糠酸氟替卡松联合，作为儿童哮喘每日一次的治疗。本研究，对使用丙酸氟替卡松（FP）对儿童哮喘控制不佳的孩子进行每日一次吸入维兰特罗、连续4周每天晚上给药，我们将对剂量、疗效、和安全性(6.25 μg, 12.5 μg and 25 μg)进行评估。
方法：这是一个在5-11岁儿童中进行的IIb期、多中心、随机、双盲、平行组、安慰剂对照的研究。这些儿童都具有持续性哮喘，需要吸入糖皮质激素和按需要短效β受体激动剂治疗。
这项研究包括4周的筛选期、4周的治疗期和1周的随访期。研究开始，患儿不再使用原有的吸入糖皮质激素（ICS）, 而是使用丙酸氟替卡松（FP）100μg每日两次。患儿随机地接受安慰剂、维兰特罗（VI）6.25μg, VI 12.5 μg 或者 VI 25 μg，每天一次。首要终点是4周的治疗后VI 25组和安慰剂组的夜间呼气峰流速基线的平均变化。次要终点包括 在第4周一秒钟用力呼气容积（FEV1）从基线的变化，无缓解药物应用和无症状天数百分比自基线的变化。安全评估包括不良事件的发生率（AES）和哮喘发作。
结果：总共入组456名患儿。首要终点为VI 25组和安慰剂组之间的的治疗差异，经校正后无显著差异（p = 0.227 ）。所以没有对其它的VI剂量组或其它的终点进行统计推断。与安慰剂相比，任何VI治疗，在FEV1谷值自基线的变化均无显著性差异；然而，VI 25组与安慰剂组相比，每周增加了0.6个无缓解药物应用日和0.7个无症状日。不良事件的发生率VI组（28-33 %）略高于安慰剂组（22%）。9个患儿在治疗期间有哮喘急性发作。
结论：与安慰剂加丙酸氟替卡松（FP）相比较，维兰特罗（VI）联合FP没有显著改善肺功能，但所有剂量评估中都显示了良好的耐受性。
（杨冬 审校）
Respir Res. 2016 Apr 5;17(1):37. doi: 10.1186/s12931-016-0353-4.
Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy.
Oliver AJ1, Covar RA2, Goldfrad CH3, Klein RM4, Pedersen SE5, Sorkness CA6, Tomkins SA3, Villarán C7, Grigg J8.
Author information
Abstract
BACKGROUND:Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatment for asthma in children. We evaluated the dose-response, efficacy, and safety of once-daily VI (6.25 μg, 12.5 μg and 25 μg) administered in the evening over 4 weeks, on background fluticasone propionate (FP) in children with asthma inadequately controlled on ICS.
METHODS:This was a Phase IIb, multicentre, randomised, double-blind, parallel-group, placebo-controlled study in children ages 5-11 years with persistent asthma on ICS and as-needed short-acting beta-agonist. The study comprised a 4-week run-in, 4-week treatment period, and 1-week follow-up. From study start, children replaced their current ICS with open-label FP 100 μg twice daily. Children were randomised to receive placebo, VI 6.25 μg, VI 12.5 μg or VI 25 μg once daily. Primary endpoint was treatment difference between VI 25 and placebo groups in mean change from baseline in evening peak expiratory flow averaged over the 4-week treatment. Secondary endpoints included change from baseline in trough forced expiratory volume in one second (FEV1) at Week 4 and change from baseline in percentage of rescue-free and symptom-free 24-h periods. Safety assessments included incidence of adverse events (AEs) and asthma exacerbations.
RESULTS:In total, 456 children comprised the intention-to-treat population. The adjusted treatment difference between VI 25 and placebo groups for the primary endpoint was not statistically significant (p = 0.227) so no statistical inference was made for other VI dose comparisons or other endpoints. No difference in change from baseline in trough FEV1 was observed for any VI treatments versus placebo; however, VI 25 resulted in an additional 0.6 rescue-free days and 0.7 symptom-free days per week versus placebo. The incidence of AEs was slightly higher in the VI groups (28-33 %) versus placebo (22 %). Nine children experienced asthma exacerbations during the treatment period.
CONCLUSION:VI plus FP did not result in significant improvements in lung function versus placebo plus FP, but was well tolerated at all doses assessed.
TRIAL REGISTRATION:NCT01573767 (ClinicalTrials.gov).
KEYWORDS:Asthma; Children; Dose response; Efficacy; Fluticasone propionate; Safety; Vilanterol
Respir Res. 2016 Apr 5;17(1):37. doi: 10.1186/s12931-016-0353-4.
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