The Efficacy and Safety of Salmeterol/Fluticasone Propionate vs Atropium/Albuterol in Patients COPD

* This is a 12-week, multicentre,randomized,open-label,active-controlled, paralleled-group study.
* Chinese patients aged ≥40 years with moderate-to-severe COPD are eligible for this study.

1. If satisfying the entry criteria, patients enter an 8 to 14 day run-in period,and replace previous bronchodilators with inhaled or nebulized Salbutamol.
2. Patients record daily severity ratings for daytime symptoms of shortness of breath, tiredness, activity limitation, frustration with symptoms, and night-time sleep symptoms on daily cards.
3. Each symptom is rated using 0-100 visual analog scal (VAS). For overall assessment of daytime symptoms, a combined symptom score is obtained by adding VAS scores for shortness of breath, tiredness, activity limitation, frustration with symptoms.
4. Patients are required to be symptomatic as demonstrated by a combined daytime symptom score of 120 on at least 4 of the 7 days prior to randomization.

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1. Eligible patients will be randomized (1:1) to the following 2 treatments for 12 weeks.

1. Inhaled Salmeterol/Fluticasone propionate 50/500ug twice daily or inhaled IB/ALB 36/206ug QID.
2. Salbutamol will be provided for relief of symptoms on an "as required" basis during the whole 12 weeks.
2. A Follow-up visit will be conducted 2 weeks after completion of treatment/early withdrawal to assess for any adverse effects after discontinuing study treatment.

• Salmeterol/Fluticasone Propionate (Drug), also known as Combivent, Salbutamol Aerosol: Salmeterol/Fluticasone 50/500ug twice daily Duration:12 weeks

Primary outcomes

• pre-broncholidator FEV1 [at 12 weeks]: Change from Baseline in pre-broncholidator FEV1 at 12 weeks

Secondary outcomes

• post-broncholidator FEV1 [at 12 weeks]: Change from Baseline in post-broncholidator FEV1 at 12 weeks
• Morning PEF, inspiration capacity (IC) and Residual Volume (RV) [at 12 weeks]: Change from Baseline in morning PEF, inspiration capacity (IC) and Residual Volume (RV)at 12 weeks
• Overall daytime symptom score, reliever medication use,SGRQ and BODY index [at 12 weeks]: Change from Baseline in overall daytime symptom score, reliever medication use,SGRQ and BODY index at 12 weeks
• Percent of symptom-free nights, sleep symptoms, nighttime awakenings due to respiratory symptoms [at 12 weeks]: Change from Baseline in percent of symptom-free nights, sleep symptoms, nighttime awakenings due to respiratory symptoms at 12 weeks
• Biomarkers: serum Clara cell 16 (CC-16) protein and serum surfactant protein D (SPD) [at 12 weeks]: Change from Baseline in biomarkers: serum Clara cell 16 (CC-16) protein and serum surfactant protein D (SPD) at 12 weeks
• participants with adverse events and COPD exacerbations [at 12 weeks]: Change from Baseline in number of participants with adverse events and COPD exacerbations at 12 weeks

Sex: All, ages: 40 Years to 79 Years

Inclusion Criteria:

* Chinese male or female outpatients aged 40 to 79 years, inclusive
* Patients with an established diagnosis of COPD, defined as GOLD guideline postbronchodilation FEV1/FVC ratio of <70%, AND Postbronchodilation FEV1% predicted ranged from ≥25 to ≤70.
* A cigarette smoking history of 10 pack-years
* Use of oral theophylline, or any other inhaled medications other than LABA, LAMA, or ICS for≥30 days (e.g. SABA, SAMA)
* Patients who are able to use Accuhaler device and relief medication
* Patients willing to give informed consent to participate in the study and comply to study protocol
* Eligible female on child-bearing potentia

Exclusion Criteria:

* Patients with concurrent respiratory disorders (e.g. asthma) other than COPD
* Patients with a requirement for regular or long term oxygen therapy (>12h/d)
* Patients who used inhaled or oral steroids within 30 days of screening
* Patients who had a respiratory tract infection requiring antibiotics within 14 days of screening
* Patients with a moderate-to-severe COPD exacerbation within 30 days of screening
* Patients with any significant medical condition or disease that would place patients at risk or interfere with the study evaluation.
* Patients who used some inhibitory agents (e.g. b blockers) within 14 days of screening
* Female patients who is pregnant or may be pregnant in the study duration

• Chunxue C BAI, Doctor, Principal investigator, Fudan University