Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Precision for Medicine, Oncology and Rare Disease, Carlsbad, CA, United States of America.
PLoS One. 2020 Dec 28;15(12):e0242945. doi: 10.1371/journal.pone.0242945. eCollection 2020.
Emerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints?
Multicentre double-blind randomized clinical trial. Adults experiencing a pulmonary exacerbation of CF being treated with standard care that included aminoglycoside therapy were randomized equally to a concomitant 14-day course of placebo, or one of 5 dosing regimens of cysteamine. Outcomes were recorded on days 0, 7, 14 and 21 and included sputum bacterial load and the patient reported outcome measures (PROMs): Chronic Respiratory Infection Symptom Score (CRISS), the Cystic Fibrosis Questionnaire-Revised (CFQ-R); FEV1, blood leukocyte count, and inflammatory markers. Eighty nine participants in fifteen US and EU centres were randomized, 78 completed the 14-day treatment period. Cysteamine had no significant effect on sputum bacterial load, however technical difficulties limited interpretation. The most consistent findings were for cysteamine 450mg twice daily that had effects additional to that observed with placebo, with improved symptoms, CRISS additional 9.85 points (95% CI 0.02, 19.7) p = 0.05, reduced blood leukocyte count by 2.46x109 /l (95% CI 0.11, 4.80), p = 0.041 and reduced CRP by geometric mean 2.57 nmol/l (95% CI 0.15, 0.99), p = 0.049.
In this exploratory study cysteamine appeared to be safe and well-tolerated. Future pivotal trials investigating the utility of cysteamine in pulmonary exacerbations of CF need to include the cysteamine 450mg doses and CRISS and blood leukocyte count as outcome measures.
NCT03000348; www.clinicaltrials.gov.
新出现的数据表明半胱胺可能作为囊性纤维化（CF）肺部恶化的辅助治疗，这仍然是一个主要的临床挑战。目前尚无研究探讨半胱胺在 CF 肺部恶化中的应用。本探索性随机临床试验旨在回答以下问题：在未来作为 CF 肺部恶化辅助治疗的半胱胺关键性试验中，应该测试哪些候选半胱胺给药方案，以及哪些是最合适的、具有临床意义的终点作为终点指标？
多中心、双盲、随机临床试验。正在接受包括氨基糖苷类治疗在内的标准治疗的 CF 肺部恶化的成年人被随机平均分配到为期 14 天的安慰剂同期治疗组，或接受 5 种半胱胺治疗方案之一。结果在第 0、7、14 和 21 天记录，包括痰细菌负荷和患者报告的结局指标（PROMs）：慢性呼吸道感染症状评分（CRISS）、囊性纤维化问卷修订版（CFQ-R）；FEV1、白细胞计数和炎症标志物。在美国和欧盟的 15 个中心有 89 名参与者被随机分组，78 名参与者完成了 14 天的治疗期。半胱胺对痰细菌负荷没有显著影响，但技术困难限制了其解释。最一致的发现是每天两次给予 450mg 半胱胺，除了观察到安慰剂的效果外，还具有改善的症状、CRISS 额外增加 9.85 分（95%CI 0.02，19.7），p = 0.05，白细胞计数减少 2.46x109 /l（95%CI 0.11，4.80），p = 0.041，CRP 几何平均值降低 2.57 nmol/l（95%CI 0.15，0.99），p = 0.049。
在这项探索性研究中，半胱胺似乎是安全且耐受良好的。未来调查半胱胺在 CF 肺部恶化中的应用的关键性试验需要包括 450mg 半胱胺剂量和 CRISS 和白细胞计数作为结局指标。
NCT03000348；www.clinicaltrials.gov。
