布地奈德-福莫特罗缓解治疗与布地奈德维持加特布他林缓解治疗成人轻中度哮喘：一项52周非盲多中心随机对照试验
2019/10/17
摘要
背景：在轻度成人哮喘患者中，与短效β受体激动剂（SABA）缓解剂治疗相比，吸入皮质类固醇与快速起效长效β受体激动剂（LABA）联合的单药治疗可减少疾病严重加重。我们研究比较了布地奈德-福莫特罗联合治疗与布地奈德维持加特布他林按需治疗的疗效。
方法：我们在新西兰的15个基层保健或医院临床试验单位和基层保健机构中进行了为期52周，开放标签，平行组，多中心，优越性，随机对照试验。参与者为18-75岁的成年人，自我报告的医生诊断为哮喘，他们在过去12周内使用SABA缓解症状，有或没有维持低至中等剂量的吸入皮质类固醇。我们随机分配参与者（1：1）至布地奈德200μg-福莫特罗6μg 都宝（按需吸入一次缓解症状）缓解治疗组或维持布地奈德200μg都宝（每天吸入一次）加特布他林250μg都宝（按需要吸入两次）组。参与者和调查员对分组非盲；统计人员对主要结果的分析做盲法处理。计划进行六次研究访问：随机分组，以及第4周期，第16周期，第28周期，第40周期和第52周。主要结果是每位患者每年严重急性发作的次数（严重急性发作定义为因哮喘使用全身性皮质类固醇激素治疗至少3天，或由于哮喘需要入院或急诊科就诊应用全身性皮质类固醇）。安全性分析包括所有接受过至少一剂研究治疗的参与者。该试验在澳大利亚新西兰临床试验注册处注册，编号为ACTRN12616000377437。
发现：在2016年5月4日至2017年12月22日期间，我们分配了890名参与者进行治疗，其中包括885名符合条件的参与者：437人分配到布地奈德-福莫特罗按需组，448人分配到布地奈德维持加特布他林按需组。布地奈德-福莫特罗按需组每位患者每年严重急性发作低于布地奈德维持加特布他林按需组（每位患者每年的绝对率0.119 vs 0.172;相对率0.69,95％CI 0.48-1.00; p = 0.049）。鼻咽炎是两组中最常见的不良事件，布地奈德-福莫特罗按需组440名患者中的154名（35％）和布地奈德维持加特布他林按需组448名患者中的144名（32％）。
解读：在成人轻中度哮喘患者中，布地奈德-福莫特罗按需使用在预防严重急性发作方面比维持低剂量布地奈德加按需使用特布他林更有效。该研究结果支持2019年全球哮喘倡议的建议，即轻度哮喘患者吸入皮质类固醇-福莫特罗缓解治疗是每天低剂量皮质类固醇吸入治疗的替代疗法。
Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trial.
Hardy J, Baggott C, Fingleton J, Reddel HK, Hancox RJ, Harwood M, Corin A, Sparks J, Hall D, Sabbagh D, Mane S, Vohlidkova A, Martindale J, Williams M, Shirtcliffe P, Holliday M, Weatherall M, Beasley R; PRACTICAL study team.
Abstract
BACKGROUND:In adults with mild asthma, a combination of an inhaled corticosteroid with a fast-onset long-acting β-agonist (LABA) used as reliever monotherapy reduces severe exacerbations compared with short-acting β-agonist (SABA) reliever therapy. We investigated the efficacy of combination budesonide-formoterol reliever therapy compared with maintenance budesonide plus as-needed terbutaline.
METHODS:We did a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial at 15 primary care or hospital-based clinical trials units and primary care practices in New Zealand. Participants were adults aged 18-75 years with a self-reported doctor's diagnosis of asthma who were using SABA for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids in the previous 12 weeks. We randomly assigned participants (1:1) to either reliever therapy with budesonide 200 μg-formoterol 6 μg Turbuhaler (one inhalation as needed for relief of symptoms) or maintenance budesonide 200 μg Turbuhaler (one inhalation twice daily) plus terbutaline 250 μg Turbuhaler (two inhalations as needed). Participants and investigators were not masked to group assignment; the statistician was masked for analysis of the primary outcome. Six study visits were scheduled: randomisation, and weeks 4, 16, 28, 40, and 52. The primary outcome was the number of severe exacerbations per patient per year analysed by intention to treat (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids). Safety analyses included all participants who had received at least one dose of study treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616000377437.
FINDINGS:Between May 4, 2016, and Dec 22, 2017, we assigned 890 participants to treatment and included 885 eligible participants in the analysis: 437 assigned to budesonide-formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. Severe exacerbations per patient per year were lower with as-needed budesonide-formoterol than with maintenance budesonide plus terbutaline as needed (absolute rate per patient per year 0·119 vs 0·172; relative rate 0·69, 95% CI 0·48-1·00; p=0·049). Nasopharyngitis was the most common adverse event in both groups, occurring in 154 (35%) of 440 patients receiving as-needed budesonide-formoterol and 144 (32%) of 448 receiving maintenance budesonide plus terbutaline as needed.
INTERPRETATION:In adults with mild to moderate asthma, budesonide-formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid-formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma.
背景：在轻度成人哮喘患者中，与短效β受体激动剂（SABA）缓解剂治疗相比，吸入皮质类固醇与快速起效长效β受体激动剂（LABA）联合的单药治疗可减少疾病严重加重。我们研究比较了布地奈德-福莫特罗联合治疗与布地奈德维持加特布他林按需治疗的疗效。
方法：我们在新西兰的15个基层保健或医院临床试验单位和基层保健机构中进行了为期52周，开放标签，平行组，多中心，优越性，随机对照试验。参与者为18-75岁的成年人，自我报告的医生诊断为哮喘，他们在过去12周内使用SABA缓解症状，有或没有维持低至中等剂量的吸入皮质类固醇。我们随机分配参与者（1：1）至布地奈德200μg-福莫特罗6μg 都宝（按需吸入一次缓解症状）缓解治疗组或维持布地奈德200μg都宝（每天吸入一次）加特布他林250μg都宝（按需要吸入两次）组。参与者和调查员对分组非盲；统计人员对主要结果的分析做盲法处理。计划进行六次研究访问：随机分组，以及第4周期，第16周期，第28周期，第40周期和第52周。主要结果是每位患者每年严重急性发作的次数（严重急性发作定义为因哮喘使用全身性皮质类固醇激素治疗至少3天，或由于哮喘需要入院或急诊科就诊应用全身性皮质类固醇）。安全性分析包括所有接受过至少一剂研究治疗的参与者。该试验在澳大利亚新西兰临床试验注册处注册，编号为ACTRN12616000377437。
发现：在2016年5月4日至2017年12月22日期间，我们分配了890名参与者进行治疗，其中包括885名符合条件的参与者：437人分配到布地奈德-福莫特罗按需组，448人分配到布地奈德维持加特布他林按需组。布地奈德-福莫特罗按需组每位患者每年严重急性发作低于布地奈德维持加特布他林按需组（每位患者每年的绝对率0.119 vs 0.172;相对率0.69,95％CI 0.48-1.00; p = 0.049）。鼻咽炎是两组中最常见的不良事件，布地奈德-福莫特罗按需组440名患者中的154名（35％）和布地奈德维持加特布他林按需组448名患者中的144名（32％）。
解读：在成人轻中度哮喘患者中，布地奈德-福莫特罗按需使用在预防严重急性发作方面比维持低剂量布地奈德加按需使用特布他林更有效。该研究结果支持2019年全球哮喘倡议的建议，即轻度哮喘患者吸入皮质类固醇-福莫特罗缓解治疗是每天低剂量皮质类固醇吸入治疗的替代疗法。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Pediatr Health Care. 2016,11(5):112-123.)
(J Pediatr Health Care. 2016,11(5):112-123.)
Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trial.
Hardy J, Baggott C, Fingleton J, Reddel HK, Hancox RJ, Harwood M, Corin A, Sparks J, Hall D, Sabbagh D, Mane S, Vohlidkova A, Martindale J, Williams M, Shirtcliffe P, Holliday M, Weatherall M, Beasley R; PRACTICAL study team.
Abstract
BACKGROUND:In adults with mild asthma, a combination of an inhaled corticosteroid with a fast-onset long-acting β-agonist (LABA) used as reliever monotherapy reduces severe exacerbations compared with short-acting β-agonist (SABA) reliever therapy. We investigated the efficacy of combination budesonide-formoterol reliever therapy compared with maintenance budesonide plus as-needed terbutaline.
METHODS:We did a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial at 15 primary care or hospital-based clinical trials units and primary care practices in New Zealand. Participants were adults aged 18-75 years with a self-reported doctor's diagnosis of asthma who were using SABA for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids in the previous 12 weeks. We randomly assigned participants (1:1) to either reliever therapy with budesonide 200 μg-formoterol 6 μg Turbuhaler (one inhalation as needed for relief of symptoms) or maintenance budesonide 200 μg Turbuhaler (one inhalation twice daily) plus terbutaline 250 μg Turbuhaler (two inhalations as needed). Participants and investigators were not masked to group assignment; the statistician was masked for analysis of the primary outcome. Six study visits were scheduled: randomisation, and weeks 4, 16, 28, 40, and 52. The primary outcome was the number of severe exacerbations per patient per year analysed by intention to treat (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids). Safety analyses included all participants who had received at least one dose of study treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616000377437.
FINDINGS:Between May 4, 2016, and Dec 22, 2017, we assigned 890 participants to treatment and included 885 eligible participants in the analysis: 437 assigned to budesonide-formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. Severe exacerbations per patient per year were lower with as-needed budesonide-formoterol than with maintenance budesonide plus terbutaline as needed (absolute rate per patient per year 0·119 vs 0·172; relative rate 0·69, 95% CI 0·48-1·00; p=0·049). Nasopharyngitis was the most common adverse event in both groups, occurring in 154 (35%) of 440 patients receiving as-needed budesonide-formoterol and 144 (32%) of 448 receiving maintenance budesonide plus terbutaline as needed.
INTERPRETATION:In adults with mild to moderate asthma, budesonide-formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid-formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma.
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