Intermittent montelukast in children aged 10 months to 5 years with wheeze (WAIT trial): a multicentre, randomised, placebo-controlled trial.
Intermittent montelukast in children aged 10 months to 5 years with wheeze (WAIT trial): a multicentre, randomised, placebo-controlled trial.
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DOI：
10.1016/s2213-2600(14)70186-9
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发表时间：
2014-10
影响因子：
76.2
通讯作者：
Grigg, Jonathan
中科院分区：
文献类型：
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作者：
Nwokoro, Chinedu;Pandya, Hitesh;Turner, Stephen;Eldridge, Sandra;Griffiths, Christopher J.;Vulliamy, Tom;Price, David;Sanak, Marek;Holloway, John W.;Brugha, Rossa;Koh, Lee;Dickson, Iain;Rutterford, Clare;Grigg, Jonathan
间歇性孟鲁司特治疗幼儿喘息的有效性尚不清楚。我们的目的是评估间歇性孟鲁司特是否比安慰剂更好地治疗这个年龄组的喘息。由于花生四烯酸5-脂氧合酶（ALOX5）基因启动子中sp1结合基序的拷贝数（5/ 5,5 /x或x/x，其中x不等于5）改变了成人对孟鲁司特的反应，因此我们按该基因型进行分层。我们在2010年10月1日至2013年12月20日期间在英格兰和苏格兰的21个初级医疗点和41个二级医疗点进行了这项多中心、平行组、随机、安慰剂对照试验。有两次或两次以上喘息发作的10个月至5岁的儿童被分配到5/5或5/x+x/x ALOX5启动子基因型层，然后通过排列阻断计划（大小10）随机分配（1:1），接受父母在12个月内每次喘息发作时给予的间歇性孟鲁司特或安慰剂。临床调查员和家长按治疗组和基因型分层分组。主要结局是因喘息发作而出现的计划外就医人数。分析的目的是治疗。该试验已在ClinicalTrials.gov注册，编号NCT01142505。我们随机分配1358名儿童接受孟鲁司特（n=669）或安慰剂（n=677）。12名（1%）儿童撤回同意。1308名（96%）儿童的主要结局数据。孟鲁司特组和安慰剂组患儿因喘息发作而出现的非计划医疗出勤率无差异（mean 2.0 [SD 2.6] vs . 2.3[2.7]；发病率比[IRR] 0.88, 95% CI: 0.77 - 1.01; p= 0.06）。与安慰剂相比，孟鲁司特组5/5组患儿因喘息发作的非计划医疗出勤率降低（2·0 [2.7]vs 2·4 [3.0];IRR 0.80, 95% CI 0.68 - 0.95; p= 0.01），但5/x+x/x组患儿无此现象（2·0 [2.5]vs 2·0[2.3];1.03,0.83 - 1·29;p= 0.79, pinteraction= 0.08）。我们记录了一个严重的不良事件，这是一个分配给安慰剂的孩子的皮肤反应。我们的研究结果显示间歇性孟鲁司特对患有喘息的幼儿没有明显的益处。然而，5/5 ALOX5启动子基因型可能鉴定出孟鲁司特反应亚组。医学研究理事会（联合王国）和国家健康研究所。
The effectiveness of intermittent montelukast for wheeze in young children is unclear. We aimed to assess whether intermittent montelukast is better than placebo for treatment of wheeze in this age group. Because copy numbers of the Sp1-binding motif in the arachidonate 5-lipoxygenase (ALOX5) gene promoter (either 5/5, 5/x, or x/x, where x does not equal 5) modifies response to montelukast in adults, we stratified by this genotype. We did this multicentre, parallel-group, randomised, placebo-controlled trial between Oct 1, 2010, and Dec 20, 2013, at 21 primary care sites and 41 secondary care sites in England and Scotland. Children aged 10 months to 5 years with two or more wheeze episodes were allocated to either a 5/5 or 5/x+x/x ALOX5 promoter genotype stratum, then randomly assigned (1:1) via a permuted block schedule (size ten), to receive intermittent montelukast or placebo given by parents at each wheeze episode over a 12 month period. Clinical investigators and parents were masked to treatment group and genotype strata. The primary outcome was number of unscheduled medical attendances for wheezing episodes. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01142505. We randomly assigned 1358 children to receive montelukast (n=669) or placebo (n=677). Consent was withdrawn for 12 (1%) children. Primary outcome data were available for 1308 (96%) children. There was no difference in unscheduled medical attendances for wheezing episodes between children in the montelukast and placebo groups (mean 2·0 [SD 2·6] vs 2·3 [2·7]; incidence rate ratio [IRR] 0·88, 95% CI: 0·77–1·01; p=0·06). Compared with placebo, unscheduled medical attendances for wheezing episodes were reduced in children given montelukast in the 5/5 stratum (2·0 [2·7] vs 2·4 [3·0]; IRR 0·80, 95% CI 0·68–0·95; p=0·01), but not in those in the 5/x+x/x stratum (2·0 [2·5] vs 2·0 [2·3]; 1·03, 0·83–1·29; p=0·79, pinteraction=0·08). We recorded one serious adverse event, which was a skin reaction in a child allocated to placebo. Our findings show no clear benefit of intermittent montelukast in young children with wheeze. However, the 5/5 ALOX5 promoter genotype might identify a montelukast-responsive subgroup. Medical Research Council (UK) and National Institute for Health Research.