Long-Term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial
Long-Term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial
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DOI：
10.1164/rccm.201803-0405oc
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发表时间：
2018-08-01
影响因子：
24.7
通讯作者：
Wedzicha, Jadwiga A.
中科院分区：
文献类型：
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作者：
Chapman, Kenneth R.;Hurst, John R.;Wedzicha, Jadwiga A.
基本原理：目前还没有关于长期三联疗法患者在没有频繁加重的情况下停用吸入性糖皮质激素的研究。目的：评价慢性阻塞性肺疾病（COPD）非频繁加重患者从长期三联疗法直接降级至茚达特罗/格隆溴铵的疗效和安全性。方法：这项为期26周的随机、双盲、三重模拟研究评估了从长期三联疗法到茚达特罗/格隆溴铵的直接变化（110/50 μ g，每日一次）或继续三联治疗（噻托溴铵[18 μ g]每日一次+沙美特罗/丙酸氟替卡松复方制剂[50/500 μ g]每日两次）治疗中度至中度非频繁加重患者重度COPD。主要终点为FEV 1谷值较基线变化的非劣效性。中度或重度急性加重预定义的次要endpoints.Measurements和主要结果：共有527例患者随机分为茚达特罗/格隆铵和526三联疗法。停用吸入性皮质类固醇导致FEV 1谷值降低226 ml（95%置信区间，253 - 1 ml），置信限超过非劣效性界值250 ml。治疗组间中度或重度COPD急性加重的年发生率无差异（率比，1.08; 95%置信区间，0.83 - 1.40）。基线时血嗜酸性粒细胞>= 300个/μ l的患者表现出更大的肺功能丧失和更高的急性加重风险。不良事件在两个groups.Conclusions：在慢性阻塞性肺疾病患者没有频繁的急性发作的长期三联治疗，直接降级为茚达特罗/格隆溴铵导致肺功能的小幅度下降，在急性发作没有差异。血嗜酸性粒细胞>= 300/μ l的患者急性加重风险较高，提示这些患者可能从三联治疗中获益。
Rationale: There are no studies on withdrawal of inhaled corticosteroids in patients on long-term triple therapy in the absence of frequent exacerbations.Objectives: To evaluate the efficacy and safety of direct de-escalation from long-term triple therapy to indacaterol/glycopyrronium in nonfrequently exacerbating patients with chronic obstructive pulmonary disease (COPD).Methods: This 26-week, randomized, double-blind, triple-dummy study assessed the direct change from long-term triple therapy to indacaterol/glycopyrronium (110/50 mu g once daily) or continuation of triple therapy (tiotropium [18 mu g] once daily plus combination of salmeterol/fluticasone propionate [50/500 mu g] twice daily) in nonfrequently exacerbating patients with moderate-to-severe COPD. Primary endpoint was noninferiority on change from baseline in trough FEV1. Moderate or severe exacerbations were predefined secondary endpoints.Measurements and Main Results: A total of 527 patients were randomized to indacaterol/glycopyrronium and 526 to triple therapy. Inhaled corticosteroids withdrawal led to a reduction in trough FEV1 of 226 ml (95% confidence interval, 253 to 1 ml) with confidence limits exceeding the noninferiority margin of 250 ml. The annualized rate of moderate or severe COPD exacerbations did not differ between treatments (rate ratio, 1.08; 95% confidence interval, 0.83 to 1.40). Patients with >= 300 blood eosinophils/mu l at baseline presented greater lung function loss and higher exacerbation risk. Adverse events were similar in the two groups.Conclusions: In patients with COPD without frequent exacerbations on long-term triple therapy, the direct de-escalation to indacaterol/glycopyrronium led to a small decrease in lung function, with no difference in exacerbations. The higher exacerbation risk in patients with >= 300 blood eosinophils/mu l suggests that these patients are likely to benefit from triple therapy.