A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants
A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants
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DOI：
10.1542/peds.103.2.414
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发表时间：
1999-02-01
期刊：
影响因子：
8
通讯作者：
Walton-Bowen, K
中科院分区：
文献类型：
--
作者：
Baker, JW;Mellon, M;Walton-Bowen, K
理由。局部给药如吸入性皮质类固醇被推荐用于治疗哮喘，但在美国没有适用于婴儿和幼儿的制剂。这是一项为期12周的多中心、双盲、随机、平行组研究，比较了480例年龄6个月至8岁的中度持续性哮喘婴儿和儿童（64%为男孩）接受布地奈德吸入混悬液（BIS）或安慰剂4种给药方案的疗效和安全性。约30%的儿童既往接受吸入性皮质类固醇治疗，但在研究前停用。活性治疗包括BIS 0.25 mg每日一次（QD）、0.25 mg每日两次（BID）、0.5 mg BID或1.0 mg QD。通过每天两次在家中记录哮喘症状评分和急救药物的使用情况，以及因哮喘恶化和/或需要全身性类固醇而中止研究来评估疗效。对于能够进行这些测试的儿童，每天两次在日记中记录峰值流量测量值，并在诊所访视时记录肺量测定。通过报告的不良事件和皮质醇测试（促肾上腺皮质激素刺激）对一部分患者的安全性进行评估。入组患者的平均哮喘持续时间为34个月;平均哮喘症状评分与1.3相似（0-3分）。与安慰剂相比，BIS的所有给药方案在哮喘控制的各种临床疗效指标方面均产生了统计学显著性改善。使用的最低剂量0.25 mg QD有效，但疗效参数少于其他剂量。对于所有BIS治疗方案，在治疗第2周时观察到活性药物治疗组和安慰剂组日间和夜间症状评分分离。在能够进行肺功能检查的儿童亚组中，与安慰剂组相比，在大多数活性治疗组中观察到峰值流量测量值显著增加。所有治疗组均显示1秒用力呼气量的数值改善，但仅0.5 mg BID剂量与安慰剂组有显著差异。布地奈德治疗组与安慰剂组相比，在治疗前和治疗结束时接受皮质醇检测的儿童亚组中，整个组的不良事件和对促肾上腺皮质激素的反应没有差异。本研究的结果表明，BIS在多次剂量范围内对中度持续性哮喘的婴幼儿有效且安全，QD给药是处方医生应考虑的重要选择。
Rationale. Topical antiinflammatory medications such as inhaled corticosteroids are recommended for therapy of asthma, but no formulation suitable for administration to infants and young children is available in the United States.Methods. This was a 12-week, multicenter, double-blind, randomized, parallel-group study comparing the efficacy and safety of four dosing regimens of budesonide inhalation suspension (BIS) or placebo in 480 asthmatic infants and children (64% boys), ages 6 months to 8 years, with moderate persistent asthma, Approximately 30% of children were previously on inhaled corticosteroids that were discontinued before the study. Active treatments were comprised of BIS 0.25 mg once daily (QD), 0.25 mg twice a day (BID), 0.5 mg BID, or 1.0 mg QD. Efficacy was assessed by twice daily recording at home of asthma symptom scores and use of rescue medication, and discontinuation from the study because of worsening asthma and/or a requirement for systemic steroids. Peak flow measurements were recorded twice daily on diary and spirometry was recorded at clinic visits for those children able to perform these tests. Safety was assessed by reported adverse events and by cortisol testing (adrenocorticotropic hormone stimulation) in a subset of patients.Results. Patients enrolled had an average duration of asthma of 34 months;the mean asthma symptom score was similar to 1.3 (scale of 0-3). All dosing regimens with BIS produced statistically significant improvement in various clinical efficacy measures for asthma control compared with placebo. The lowest dose used, 0.25 mg QD, was efficacious but with fewer efficacy parameters than seen with the other doses administered. Separation between active treatment and placebo in daytime and nighttime symptom scores were observed by week 2 of treatment for all BIS treatment regimens. A significant increase in peak flow measurement was observed in most active treatment groups compared with placebo in the subset of children able to do pulmonary function testing. All treatment groups showed numerical improvement in forced expiratory volume in 1 second but only the 0.5-mg BID dose was significantly different from placebo. Adverse events for the entire group and response to adrenocorticotropic hormone in a subgroup of children who underwent cortisol testing before and at the end of the treatment period were no different in budesonide-treated patients in comparison to placebo.Conclusion. Results of this study demonstrate that BIS is effective and safe for infants and young children with moderate persistent asthma in a multiple dose range, and that QD dosing is an important option to be considered by the prescribing physician.