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单次吸入三联疗法治疗不受控制哮喘可有效改善肺功能
作者:小柯机器人 发布时间:2019/10/1 15:43:52

德国罗斯托克大学医学院Johann Christian Virchow研究小组分析了单次吸入三联疗法治疗不受控制哮喘的疗效。这一研究成果2019年9月30日在线发表在《柳叶刀》上。

研究组进行了两项平行组、双盲、随机、主动对照的临床3期试验,其中TRIMARAN项目在16个国家的171个点进行,TRIGGER项目在17个国家的221个点进行。参与者年龄为18-75岁,患有不受控制的哮喘,在过去1年中至少发作一次,之前曾用吸入性皮质类固醇+长效β2受体激动剂治疗过。所有参与者均先进行2周的丙酸倍氯米松(BDP)+富马酸福莫特罗(FF)治疗,之后再随机分组。

2016年2月17日至2018年5月17日,TRIMARAN项目共招募了1155名参与者,其中579名进行BDP/FF+格隆铵(G)治疗,576名进行BDP/FF治疗。2014年4月6日至2018年5月28日,TRIGGER项目共招募了1437名参与者,其中573名进行BDP/FF/G治疗,576名进行BDP/FF治疗,288名进行BDP/FF+噻托溴铵治疗。

治疗第26周时,与BDP/FF组相比,TRIMARAN项目和TRIGGER项目中BDP/FF/G组的一秒用力呼气量(FEV 1)分别增加了57mL和73mL,中重度加重率分别降低了15%和12%。共有4名患者发生与治疗相关的严重不良事件,其中TRIMARAN项目的BDP/FF/G组发生1例,TRIGGER项目的BDP/FF/G组发生1例,BDP/FF组发生2例。TRIMARAN项目的BDP/FF/G组中有3例患者因治疗死亡,而TRIGGER项目的BDP/FF/G组和BDP/FF组各有1例死亡。

总之,对于不受控制的哮喘,吸入性皮质类固醇+长效β2受体激动剂+长效毒蕈碱拮抗剂可有效改善肺功能,减少恶化率。

附:英文原文

Title: Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials

Author: Johann Christian Virchow, Piotr Kuna, Pierluigi Paggiaro, Alberto Papi, Dave Singh, Sandrine Corre, Florence Zuccaro, Andrea Vele, Maxim Kots, George Georges, Stefano Petruzzelli, Giorgio Walter Canonica

Issue&Volume: 30 September 2019

Abstract: 

Background

To date, no studies have assessed the efficacy of single-inhaler triple therapy in asthma. Here we report on two studies that compared the single-inhaler extrafine combination of beclometasone dipropionate (BDP; inhaled corticosteroid), formoterol fumarate (FF; long-acting β 2 agonist), and glycopyrronium (G; long-acting muscarinic antagonist) with the combination of BDP with FF.

Methods

Two parallel-group, double-blind, randomised, active-controlled, phase 3 trials (Triple in Asthma With Uncontrolled Patients on Medium Strength of ICS + LABA [TRIMARAN] and Triple in Asthma High Strength Versus ICS/LABA HS and Tiotropium [TRIGGER]) recruited patients from 171 sites across 16 countries (TRIMARAN), and from 221 sites across 17 countries (TRIGGER). The sites were a mixture of secondary and tertiary care centres and specialised investigation units. Eligible patients were adults (aged 18–75 years) with uncontrolled asthma, a history of one or more exacerbations in the previous year, and previously treated with inhaled corticosteroid (TRIMARAN: medium dose; TRIGGER: high dose) plus a long-acting β 2 agonist. Enrolled patients were initially treated with BDP/FF (TRIMARAN: 100 μg BDP and 6 μg FF; TRIGGER: 200 μg BDP and 6 μg FF) for 2 weeks, then randomly assigned to treatment using an interactive response technology system with a balanced block randomisation scheme stratified by country. Patients, investigators, site staff, and sponsor staff were masked to BDP/FF/G and BDP/FF assignment. In TRIMARAN, patients were randomly assigned (1:1) to 52 weeks of BDP/FF/G (100 μg BDP, 6 μg FF, and 10 μg G) or BDP/FF (100 μg BDP and 6 μg FF), two inhalations twice daily. In TRIGGER, patients were randomly assigned (2:2:1) to 52 weeks of BDP/FF/G (200 μg BDP, 6 μg FF, and 10 μg G) or BDP/FF (200 BDP and 6 μg FF), both two inhalations twice daily, or open-label BDP/FF (200 μg BDP and 6 μg FF) two inhalations twice daily plus tiotropium 2·5 μg two inhalations once daily. Coprimary endpoints for both trials (BDP/FF/G vs BDP/FF) were pre-dose forced expiratory volume in 1 s (FEV 1) at week 26 and rate of moderate and severe exacerbations over 52 weeks. Safety was assessed in all patients who received at least one dose of study treatment. These trials were registered with ClinicalTrials.gov, NCT02676076 (TRIMARAN), NCT02676089 (TRIGGER).

Findings

Between Feb 17, 2016, and May 17, 2018, 1155 patients in TRIMARAN were given BDP/FF/G (n=579) or BDP/FF (n=576). Between April 6, 2016, and May 28, 2018, 1437 patients in TRIGGER were given BDP/FF/G (n=573), BDP/FF (n=576), or BDP/FF plus tiotropium (n=288). Compared with the BDP/FF group, week 26 predose FEV 1 improved in the BDP/FF/G group by 57 mL (95% CI 15–99; p=0·0080) in TRIMARAN and by 73 mL (26–120; p=0·0025) in TRIGGER, with reductions in the rate of moderate and severe exacerbations of 15% (rate ratio 0·85, 95% CI 0·73–0·99; p=0·033) in TRIMARAN and 12% (0·88, 0·75–1·03; p=0·11) in TRIGGER. Four patients had treatment-related serious adverse events, one in TRIMARAN in the BDP/FF/G group and three in TRIGGER—one in the BDP/FF/G and two in the BDP/FF group. Three patients in the BDP/FF/G group in TRIMARAN and two patients in TRIGGER—one in the BDP/FF/G group and one in the BDP/FF group—had adverse events leading to death. None of the deaths were considered as related to treatment.

Interpretation

In uncontrolled asthma, addition of a long-acting muscarinic antagonist to inhaled corticosteroid plus long-acting β 2-agonist therapy improves lung function and reduces exacerbations.

DOI: 10.1016/S0140-6736(19)32215-9

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32215-9/fulltext

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
官方网址:http://www.thelancet.com/
投稿链接:http://ees.elsevier.com/thelancet