Tiotropium In Early Chronic Obstructive Pulmonary Disease Patients in China

Study Overview
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Brief Summary
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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.

Official Title
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Early Intervention With Tiotropium （Spiriva） in Chinese Patients With Chronic Obstructive Pulmonary Disease (COPD): a Randomized, Double-blind, Placebo-controlled, Parallel, Multicentre Trial

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Tiotropium
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: tiotropium group<br>18 mcg tiotropium, once daily, inhaled by HandiHaler | Drug: Tiotropium<br>* 18 mcg tiotropium capsule, once daily, inhaled by HandiHaler, for 24 months<br>* Other names: Spiriva;|
| Placebo Comparator: placebo group<br>matching placebo, once daily, inhaled by HandiHaler | Drug: placebo<br>* placebo, once daily, inhaled by HandiHaler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference of trough FEV1 at 24 months from baseline |  | at 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference of peak FEV1 at 24 months from baseline |  | at 24 months | 
| trough (pre-bronchodilator) FEV1 at 1, 6, 12 and 18 months |  | at 1, 6, 12 and 18 months | 
| quality of life (CAT and CCQ) |  | at 1, 3, 6, 9, 12, 15, 18 and 24 months | 
| symptom scores (mMRC dyspnoea scale) |  | at 1, 3, 6, 9, 12, 15, 18 and 24 months | 
| time to first COPD exacerbation |  | 24 months | 
| number of COPD exacerbation |  | 24 months | 
| severity of COPD exacerbation |  | 24 months | 
| Application of rescue medications |  | 24 months | 
| drop-out rate |  | 24 months | 
| adverse events |  | 24 months | 
| peak (post-bronchodilator) FEV1 at 1, 6, 12 and 18 months |  | at 1, 6, 12 and 18 months | 
| Yearly rate of decline in trough FEV1 from 1 month until completion of double-blind treatment |  | 24 months | 
| Yearly rate of decline in peak FEV1 from 1 month until completion of double-blind treatment |  | 24 months | 
| Yearly rate of decline in trough FVC from 1 month until completion of double-blind treatment |  | 24 months | 
| Yearly rate of decline in peak FVC from 1 month until completion of double-blind treatment |  | 24 months | 
| Yearly rate of decline in trough FEV1/FVC from 1 month until completion of double-blind treatment |  | 24 months | 
| Yearly rate of decline in peak FEV1/FVC from 1 month until completion of double-blind treatment |  | 24 months | 
| interval of COPD exacerbation |  | 24 months | 
| duration of COPD exacerbation |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic obstructive pulmonary disease, COPD, COPD exacerbation, treatment, tiotropium, anticholinergic, acute exacerbation of COPD (AECOPD)