“噻托溴铵长期规则治疗早期慢性阻塞性肺疾病的随机、双盲、安慰剂对照、平行分组、多中心研究”的研究方案

Early intervention with tiotropium in Chinese patients with GOLD stages Ⅰ -Ⅱ chronic obstructive pulmonary disease （Tie-COPD）： study protocol for a multicentre, double-blinded, randomised, controlled trial

研究背景随着慢性阻塞性肺疾病（COPD）的发病率与病死率的上升，它已成为世界性公共健康问题。尽管大多数患者属于早期COPD，但是对于此类患者的早期干预研究却很少。噻托溴铵可以明显改善COPD患者临床症状，减少急性加重频率。因此我们推测噻托溴铵同样可以使早期COPD患者获益，减缓疾病进展。方法与设计本研究采用为随机、双盲、安慰剂对照、平行分组、多中心临床研究的方法来评价噻托溴铵长期规则治疗早期COPD的疗效和安全性（Tiotropium In Early COPD study，Tie-COPD）。治疗期持续2年。至今共入组COPD患者839例，随机分为2组（1：1）：噻托溴铵治疗组（每日一次性吸入噻托溴铵粉剂18μg）和安慰剂对照组。监测的指标包括1秒用力呼气容积（FEV1）、健康相关生活质量、症状评分、COPD急性加重情况和药物经济学评价等。伦理／研究进度本研究已通过广州医科大学附属第一医院伦理委员会的审批。患者的招募开始于2011年11月，结束于2013年10月，共招募839例患者。最后一次随访时间为2015年11月。研究结果将在学术会议上展示并将发表在具有同行评议的学术期刊上。

Introduction Owing to the high and increasing morbidity and mortality, chronic obstructive pulmonary disease （COPD） has become a major public health problem worldwide. Although the majority of patients with COPD are in the early stages, little attention has been paid to them, in particular regarding to early intervention. Tiotropium bromide can signifieantly relieve symptoms and reduce the incidence of acute exacerbations of COPD. Therefore, we hypothesise that therapy with tiotropium bromide will benefit patients with COPD with early-stage disease. Method/analysis A randomised, double-blinded,placebo-controlled, parallel-group, multieentre clinical trial （Tiotropium In Early COPD study, Tie-COPD study） is being conducted to evaluate the efficacy and safety of long-term intervention with tiotropium in patients with COPD with earlystage disease. A total of 839 patients with COPD who satisfied the eligibility criteria were randomly assigned （ 1 ： 1 ） to receive a once daily inhaled capsule of either tiotropium bromide （ 18μg） or matching placebo for 2 years. Measurements will include forced expiratory volume in 1 s, health-related quality of life, grade degree of breathlessness related to activities, COPD exacerbations and pharmacoeconomic analysis. Ethics/dissemination This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. Recruitment started in November 2011 and ended in October 2013, with 839 patients randomised. The treatment follow-up of participants with Tie-COPD is currently ongoing and is due to finish in November 2015, The authors will disseminate the findings in peer-reviewed publications, conferences and seminar presentations. Trial registration ClinicalTrials. gov （NCT01455129）.