David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90272, USA.
Expert Rev Respir Med. 2010 Jun;4(3):279-89. doi: 10.1586/ers.10.23.
The Understanding Potential Long-term Improvements in Function with Tiotropium (UPLIFT) trial was a global 4-year randomized placebo-controlled clinical trial that evaluated the long-term impact of tiotropium bromide 18 microg once daily on the accelerated age-related decline in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV(1); co-primary end points). Secondary end points included lung function at serial clinic visits, health-related quality of life, exacerbations, exacerbation-related hospitalizations, mortality, safety and tolerability. The study was carried out in 5992 patients (75% male, mean age 65 years, 30% current smokers) with moderate-to-very severe chronic obstructive pulmonary disease who were permitted to receive prescribed treatment with long-acting beta(2)-agonists and/or inhaled corticosteroids in addition to the study drug. While the results failed to show an effect of tiotropium on the primary end points (rate of decline in pre- and post-bronchodilator FEV(1)), they did show improvements in lung function and health-related quality of life that were maintained throughout the study and a reduction in the risk of exacerbations and related hospitalizations. Tiotropium also reduced all-cause mortality in patients on treatment over the 4-year trial period and reduced lower respiratory and cardiovascular morbidity, including respiratory failure and myocardial infarction. Adverse events were consistent with the drug's known anticholinergic pharmacology.
噻托溴铵对功能长期改善的认识（UPLIFT）试验是一项全球性的 4 年随机安慰剂对照临床试验，评估了噻托溴铵 18μg 每日 1 次对支气管扩张剂预支后 1 秒用力呼气容积（FEV(1)）的加速年龄相关下降的长期影响（主要终点）。次要终点包括系列临床就诊时的肺功能、健康相关生活质量、恶化、恶化相关住院、死亡率、安全性和耐受性。该研究纳入了 5992 例（75%为男性，平均年龄 65 岁，30%为当前吸烟者）中重度至极重度慢性阻塞性肺疾病患者，这些患者除了接受研究药物外，还允许接受长效β(2)-激动剂和/或吸入皮质激素的处方治疗。尽管结果未能显示噻托溴铵对主要终点（支气管扩张剂预支后 FEV(1)的下降率）有影响，但确实显示出肺功能和健康相关生活质量的改善，这些改善在整个研究期间得以维持，恶化和相关住院的风险降低。噻托溴铵还降低了治疗 4 年试验期间的全因死亡率，并降低了下呼吸道和心血管发病率，包括呼吸衰竭和心肌梗死。不良反应与该药物已知的抗胆碱能药理学一致。
