A 2 x 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol for the CLEAR clinical trial
A 2 x 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol for the CLEAR clinical trial
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DOI：
10.1186/s13063-019-3766-9
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发表时间：
2019-12-19
期刊：
影响因子：
2.5
通讯作者：
Ionescu, Alina
中科院分区：
文献类型：
--
作者：
Bradley, Judy Martina;Anand, Rohan;Ionescu, Alina
背景：目前的支气管扩张（BE）治疗指南强调缺乏证据推荐粘液活性药物，如高渗盐水（HTS）和卡西汀，作为标准治疗的一部分来辅助痰清除。我们假设与常规治疗相比，黏液活性药物（HTS或carbocissteine，或两者联合）在52周内可有效减少急性加重。方法：这是一项为期52周、2 × 2因子、随机、开放标签的试验，旨在确定6% HTS和carbocissteine与常规治疗相比用于气道清除的临床有效性和成本效益-高渗盐水（HTS 6%）和carbocissteine用于气道清除与常规治疗（CLEAR）试验的临床和成本效益。患者将被随机分配到(1)标准治疗和每日两次雾化HTS(6%),(2)标准治疗和卡西汀（750毫克，每天3次，直到就诊3次，减少到750毫克，每天2次），(3)标准治疗和每日两次雾化HTS和卡西汀的组合，或(4)标准治疗。主要终点是52周内的平均恶化次数。主要纳入标准如下：在计算机断层扫描上诊断为BE，主要呼吸道诊断为BE，在过去一年中有两次或两次以上肺部恶化需要抗生素和每日咳痰的成年人。讨论：该试验的实用研究设计避免了与双盲试验相关的重大成本，同时优化了试验交付的其他领域的严谨性。CLEAR试验将提供证据，证明HTS、carbocissteine或两者对BE患者是否有效且具有成本效益。
Background: Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum removal as part of standard care. We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care.Methods: This is a 52-week, 2 x 2 factorial, randomized, open-label trial to determine the clinical effectiveness and cost effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care - the Clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care (CLEAR) trial. Patients will be randomised to (1) standard care and twice-daily nebulised HTS (6%), (2) standard care and carbocisteine (750 mg three times per day until visit 3, reducing to 750 mg twice per day), (3) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (4) standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria are as follows: adults with a diagnosis of BE on computed tomography, BE as the primary respiratory diagnosis, and two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum.Discussion: This trial's pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigour in other areas of trial delivery. The CLEAR trial will provide evidence as to whether HTS, carbocisteine or both are effective and cost effective for patients with BE.