A Proof-of-concept Study to Evaluate the Benefit From add-on Therapy With Montelukast Versus Salmeterol in Children With Asthma Carrying the Arg/Arg-16 beta2-receptor Genotype
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Oral montelukast is associated with reduced school absences in comparison to inhaled salmeterol over a period of 1 year in Arg/Arg-16 asthmatic children
研究概览
简要总结
The purpose of this study is to determine whether patients with asthma who carry a genotype associated with adverse outcomes with long-acting beta-2 agonists like salmeterol show greater benefit from the use of an asthma drug that works via alternative pathways like montelukast.
详细描述
Background/Rationale:
The presence of the homozygous Arg/Arg genotype at position 16 of the β2-receptor (prevalence 15-17% in UK/US populations) confers relative protection against down-regulation by endogenous catecholamines, making individuals susceptible to down-regulation and desensitization by regular exogenous β2-agonists and thereby negating the benefits from the regular use of short and long acting β2-agonists in adults with asthma. We found that, in the children receiving salmeterol, the adjusted odds ratio showed a 9 fold (p=0.003) greater risk of school absences due to asthma in the Arg/Arg group in comparison to the Gly16 carriers, with an unadjusted odds ratio of 6 (p=0.009). In the cohort not receiving salmeterol, there was no evidence of any genotype-dependent increases in school absences due to asthma (odds ratio=1). In addition, the Arg/Arg children on salmeterol had a significantly increased risk of extended school absence of over 1 week from asthma with an adjusted odds ratio of 6 (p= 0.019).
Currently, British Thoracic Society/Scottish Intercollegiate Guidelines Network recommendations suggest the use of regular long-acting β2-agonists as add on therapy in children with asthma who are inadequately controlled on inhaled steroids. The guidelines suggest the use of leukotriene antagonists (e.g. montelukast) if a combination of inhaled salmeterol and inhaled steroids fail to control symptoms.
There are 1 million children with asthma in the UK. 150,000-170,000 children carry the Arg/Arg-16 genotype.
The Arg/Arg-16 children with asthma may constitute a significant population that is likely to show better asthma control with a leukotriene antagonist in comparison to long-acting β2-agonists. We have already demonstrated that school absences constitute a suitable primary outcome measure for the testing of this hypothesis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All children and adolescents (5-18 years) with asthma in Tayside (Scotland) known:
- •To carry the Arg/Arg-16 genotype and
- •Currently on inhaled steroids and
- •Inhaled bronchodilators according to need will be telephoned or contacted through home visits to establish if they have had:
- •Any school absences from asthma or
- •Out-of-hours visits to GP/hospital visits or admissions due to asthma over the previous 12 months.
排除标准
- •The presence of serious respiratory or multi-system disease (e.g. cystic fibrosis, cancer under current treatment)
研究组 & 干预措施
1
The active comparator arm consists of Flixotide® (fluticasone propionate) via accuhaler (Diskus) dry powder inhaler device as per current inhaled steroid dose plus oral montelukast
干预措施: Salmeterol, Montelukast (Drug)
2
The placebo comparator arm consists of Seretide® (salmeterol plus equivalent dose of fluticasone) via accuhaler dry powder inhaler device as per current inhaled steroid dose plus placebo for montelukast
干预措施: Montelukast Placebo (Drug)
结局指标
主要结局
Oral montelukast is associated with reduced school absences in comparison to inhaled salmeterol over a period of 1 year in Arg/Arg-16 asthmatic children
时间窗: Every 3 months
次要结局
- Oral montelukast is associated with improved asthma specific quality-of-life in comparison to inhaled salmeterol over a period of 1 year(Every 3 months)