Clinical trial NCT01455129: Tiotropium In Early Chronic Obstructive Pulmonary Disease Patients in China
Official title: Early Intervention With Tiotropium （Spiriva） in Chinese Patients With Chronic Obstructive Pulmonary Disease (COPD): a Randomized, Double-blind, Placebo-controlled, Parallel, Multicentre Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: chronic obstructive pulmonary disease
COPD
COPD exacerbation
treatment
tiotropium
anticholinergic
acute exacerbation of COPD (AECOPD)
Lead sponsor: The First Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
name: Rundo International Pharmaceutical Research & Development Co.,Ltd.
First posted: 2011-10-19
Enrollment: 841
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chronic obstructive pulmonary disease (COPD) is one of the commonest respiratory diseases. During the early stage of COPD, patients only have mild respiratory symptoms or signs which may lead to under-diagnosis of the disease. Patients may show poor response to treatment at later stages of the disease, associated with higher mortality and incidence of re-hospitalization and disability causing burden for both the families and the society.

So far, there is no large-scale clinical trial on long-term intervention with tiotropium bromide (Spiriva) in patients with early stages of COPD (i.e. GOLD Stage I-II COPD or asymptomatic COPD). It would be of great significance for COPD prevention and treatment if the investigators could prove that tiotropium decreases the lung function decline and reverses disease progression in patients with early-stage COPD.

The investigators objective is to evaluate the efficacy of long-term intervention with tiotropium in early stage (FEV1 ≥50% predicted) COPD (difference of trough FEV1, number of exacerbations, time to first exacerbation, quality of life, etc) and relevant pharmacoeconomic endpoints.


Eligibility criteria: Inclusion Criteria:

* Age: 40-85 yrs, both male and female, with or without smoking history, receiving treatment in community hospitals or outpatient department in general hospitals
* GOLD Stage I-II COPD: FEV1/FVC\<70% and FEV1≥50% predicted, measured 20min after 400μg salbutamol inhalation
* With stable COPD: no COPD exacerbation during the latest 4 weeks prior to the recruitment
* With capability of communicating via oral conversation or written documents and signing informed consent
* With agreement to receive and are capable of participating in study related auxiliary examinations
* Capability of proper use of HandiHaler

Exclusion Criteria:

* Significant diseases other than COPD. A significant disease is defined as a disease or condition which, in the opinion of the investigator, may put the patient at risk because of participation in the study or may influence either the results of the study or the patients' ability to participate in the study
* Patients with clinically significant abnormal baseline haematology, blood biochemistry or urinary analysis, if the abnormality defines a significant disease as defined in exclusion criteria No. 1
* Patients with clinical diagnosis of lung cancer, bronchiectasis, pneumoconioses, or other single restricted ventilation
* Severe cardiovascular, neural, hepatic, renal and hematologic diseases or malignancies that may interfere with the operation of the study
* Patients with prostatic hyperplasia or bladder neck obstruction with significant symptoms, or narrow angle glaucoma
* Patients with known moderate to severe impaired renal function in the opinion of the investigator or creatinine clearance ≤50 ml/min
* Patients with history of asthma, allergic rhinitis, or who have a blood eosinophil count ≥600/mm\^3
* Patients with active pulmonary tuberculosis
* Patients with life-threatening pulmonary embolism, α1-antitrypsin deficiency, or cystic fibrosis
* History of pneumonectomy
* COPD exacerbation in 4 weeks prior to the first visit (V0), or hospitalization and/or antibiotic application and/or oral or intravenous glucocorticosteroids application is required during screening stage.
* Treated with one of the trial drugs during the 30 days or 6 half-lives prior to the first visit (V0), with the selection of the longer period
* Long-term oxygen therapy, frequent use of glucocorticosteroids orally or intravenously at unstable doses(i.e. less than six weeks on stable doses) or at doses in excess of the equivalent of 10 mg of prednisone/day, or long-term use of antibiotics
* Pregnancy, lactation or potential of pregnancy
* Planned hospitalization or blood donation during the trial
* Known hypersensitivity or intolerance to trial drugs
* History of chronic alcohol or drug abuse, or any other conditions that may impact compliance
* Involvement in other clinical studies at the same time

Primary outcomes:
measure: difference of trough FEV1 at 24 months from baseline
timeFrame: at 24 months
Secondary outcomes:
measure: difference of peak FEV1 at 24 months from baseline
timeFrame: at 24 months
measure: trough (pre-bronchodilator) FEV1 at 1, 6, 12 and 18 months
timeFrame: at 1, 6, 12 and 18 months
measure: quality of life (CAT and CCQ)
timeFrame: at 1, 3, 6, 9, 12, 15, 18 and 24 months
measure: symptom scores (mMRC dyspnoea scale)
timeFrame: at 1, 3, 6, 9, 12, 15, 18 and 24 months
measure: time to first COPD exacerbation
timeFrame: 24 months
measure: number of COPD exacerbation
timeFrame: 24 months
measure: severity of COPD exacerbation
timeFrame: 24 months
measure: Application of rescue medications
timeFrame: 24 months
measure: drop-out rate
timeFrame: 24 months
measure: adverse events
timeFrame: 24 months
measure: peak (post-bronchodilator) FEV1 at 1, 6, 12 and 18 months
timeFrame: at 1, 6, 12 and 18 months
measure: Yearly rate of decline in trough FEV1 from 1 month until completion of double-blind treatment
timeFrame: 24 months
measure: Yearly rate of decline in peak FEV1 from 1 month until completion of double-blind treatment
timeFrame: 24 months
measure: Yearly rate of decline in trough FVC from 1 month until completion of double-blind treatment
timeFrame: 24 months
measure: Yearly rate of decline in peak FVC from 1 month until completion of double-blind treatment
timeFrame: 24 months
measure: Yearly rate of decline in trough FEV1/FVC from 1 month until completion of double-blind treatment
timeFrame: 24 months
measure: Yearly rate of decline in peak FEV1/FVC from 1 month until completion of double-blind treatment
timeFrame: 24 months
measure: interval of COPD exacerbation
timeFrame: 24 months
measure: duration of COPD exacerbation
timeFrame: 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital
state: Beijing
city: Chongqing
country: China
facility: Xinqiao Hospital
state: Chongqing
city: Foshan
country: China
facility: The First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical College
state: Guangdong
city: Guangzhou
country: China
facility: Liwan Hospital,Guangzhou Medical College
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Guangzhou Medical College
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong No.2 Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Panyu Center Hospital
state: Guangdong
city: Huizhou
country: China
facility: Huizhou First Hospital
state: Guangdong
city: Shaoguan
country: China
facility: Wengyuan County People's Hospital
state: Guangdong
city: Shaoguan
country: China
facility: The First People's Hospital of Shaoguan
state: Guangdong
city: Shaoguan
country: China
facility: Shaoguan Iron and Steel Group Company limited Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Sixth People's Hospital
state: Guangdong
city: Zhanjiang
country: China
facility: The second people's Hospital,Zhanjiang
state: Guangdong
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical College
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Hospital of Guiyang Medical College
state: Guizhou
city: Guiyang
country: China
facility: Guizhou People's Hospital
state: Guizhou
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital,Tongji Medical College of HUST
state: Hubei
city: Changsha
country: China
facility: The Second People's Hospital of Hunan Province
state: Hunan
city: Chenzhou
country: China
facility: Chenzhou No.1 people's Hopital
state: Hunan
city: Shanghai
country: China
facility: Shanghai Xuhui District Central Hospital
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
Study officials:
affiliation: The First Affiliated Hospital of Guangzhou Medical University
name: Nanshan Zhong, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Guangzhou Medical University
name: Pixin Ran, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhou Y, Zhong NS, Li X, Chen S, Zheng J, Zhao D, Yao W, Zhi R, Wei L, He B, Zhang X, Yang C, Li Y, Li F, Du J, Gui J, Hu B, Bai C, Huang P, Chen G, Xu Y, Wang C, Liang B, Li Y, Hu G, Tan H, Ye X, Ma X, Chen Y, Hu X, Tian J, Zhu X, Shi Z, Du X, Li M, Liu S, Yu R, Zhao J, Ma Q, Xie C, Li X, Chen T, Lin Y, Zeng L, Ye C, Ye W, Luo X, Zeng L, Yu S, Guan WJ, Ran P. Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease. N Engl J Med. 2017 Sep 7;377(10):923-935. doi: 10.1056/NEJMoa1700228.
citation: Li X, Zhou Y, Chen S, Zheng J, Zhong N, Ran P. 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. BMJ Open. 2014 Feb 18;4(2):e003991. doi: 10.1136/bmjopen-2013-003991.