Effect of Traditional Chinese Medicine on Outcomes in Patients With Severe / Very Severe COPD

Study Overview
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Brief Summary
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The aim of this study is to compare the effectiveness of two treatments for severe / very severe COPD patients: one, conventional medicine based on 2013 Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Chinese Treatment Guidelines; the other, TCM treatments and conventional medicine, which have been evaluated and have certain effect.

Detailed Description
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Patients with severe or very severe COPD are more likely to suffer repeated exacerbations and more rapidly declining lung function generating increased risk of death and time to a COPD related hospitalization. Although many therapies exist and are being developed to relieve symptoms and reduce mortality in COPD, most have only been studied in moderate to very severe COPD. There are few clinical trials to compare therapeutic alternatives in severe and very sever COPD. Furthermore, some randomized controlled trials on comprehensive Traditional Chinese medicine (TCM) interventions, especially based on the TCM patterns, have been the certain evidence for showing definite effect for COPD patients. In addition, a study about the effect of TCM on outcomes in mild and moderate COPD patients has been in progress and will be carried out in December 2014 (NCT01486186). Hence, corresponding to the mild to moderate COPD patients, The this study aims to evaluate the effectiveness of TCM on severe / very severe COPD patients. This is a multi-center, randomized, double-blind, controlled study to evaluate the effectiveness of TCM on severe / very Severe COPD patients. Following a 14 day run-in period, approximately 564 subjects will be randomly assigned to conventional medicine treatment group, TCM and conventional medicine treatment group for 52 weeks. After the 52 weeks treatment period, subjects in two treatments arms will follow-up 52 weeks. The primary outcome measure is the frequency of exacerbations. The secondary efficacy measures include all-cause mortality, FEV1, dyspnea (MMRC), exercise capacity( 6MWD), quality of life ( CAT, SF-36 and COPD-PRO), and effectiveness satisfaction with treatment(ESQ-COPD) . Safety will be assessed through the collection of adverse events. There will be a total of 9 study visits (baseline, the 13, 26, 39 and 52 weeks of the treatment, the 13, 26, 39 and 52 weeks of follow-up).

Official Title
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A Multi-center, Randomized, Double-blind, Controlled Study to Evaluate the Effectiveness of on Severe / Very Severe COPD Patients

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Salmeterol / fluticasone (Seretide®)
* Drug: Bufeijianpi granule
* Drug: Bufeiyishen granule
* Drug: Yiqizishen granule
* Drug: Placebo Bufeijianpi granule
* Drug: Placebo Bufeiyishen granule
* Drug: Placebo Yiqizishen granule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A confirmed diagnosis of severe to very severe COPD. medically stable Age between 40 and 80 years. Syndrome differentiation belongs to syndrome of deficiency of pulmonosplenic qi, syndrome of insufficiency of qi of the lung and kidney, syndrome of insufficiency of qi and yin of the lung and kidney. with a two-week wash-out period prior to randomization Without participations in other interventional trials in the previous one month. With the informed consent signed. Exclusion Criteria: Pregnant or breast-feeding women. Any psychiatric condition rendering the patient unable to understand the nature, scope and possible consequences of the study. Current respiratory disorders other than COPD (e.g., bronchiectasis, bronchial asthma, tuberculosis, lung fibrosis, pulmonary thromboembolic, diffuse panbronchiolitis). Complicated with a neuromuscular disorder, which affected the respiration. Complicated with heart failure (NYHA Class III or IV),or myocardial infarction within six months ,or unstable hemodynamics. Complicated with malignancy, congenital or acquired immune deficiency. Complicated with serious hepatic and renal diseases (liver cirrhosis, portal hypertension, bleeding of varicose veins, dialysis, or renal transplantation). Participating in other trials or allergic to the used medicine.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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 |
| --- | --- |
| Experimental: Conventional medicine+ placebo TCM<br>Patients in this group will be given conventional medicine, Salmeterol / fluticasone based on the classes of medications recommended by 2011 GOLD and Chinese Treatment Guidelines for COPD, and three placebo TCM treatment, which are which are placebo Bufeijianpi granule, placebo Bufeiyishen granule and placebo Yiqizishen granule corresponding to the three traditional Chinese syndromes in sequence, which are syndrome of deficiency of pulmono-splenic qi, syndrome of insufficiency of qi of the lung and kidney, syndrome of insufficiency of qi and yin of the lung and kidney. | Drug: Salmeterol / fluticasone (Seretide®)<br>* According to the revised 2013 GOLD, Salmeterol / fluticasone was used to severe and very severe COPD patients for 52weeks: Salmeterol / fluticasone (Seretide®, GlaxoSmithKline), 50/500 μg / dose, 60 inhalations. 50/500 μg each time, twice daily.<br>Drug: Placebo Bufeijianpi granule<br>* According to traditional Chinese syndrome differentiation and treatment, patients with syndrome of deficiency of pulmono-splenic qi will be given placebo Bufeijianpi granule, twice daily for 52 weeks for lower dosage.<br>Drug: Placebo Bufeiyishen granule<br>* According to traditional Chinese syndrome differentiation and treatment, patients with syndrome of insufficiency of qi of the lung and kidney will be given placebo Bufeiyishen granule, twice daily for 52 weeks for lower dosage.<br>Drug: Placebo Yiqizishen granule<br>* According to traditional Chinese syndrome differentiation and treatment, patients with syndrome of insufficiency of qi and yin of the lung and kidney will be given placebo Yiqizishen granule granule, twice daily for 52 weeks for lower dosage.<br>|
| Experimental: conventional medicine+ TCM<br>Patients in this group will receive Salmeterol / fluticasone based on the classes of medications recommended by 2011 GOLD and Chinese Treatment Guidelines for COPD, and three types of TCM treatment, which are Bufeijianpi granule, Bufeiyishen granule and Yiqizishen granule. A herbal extract twice daily for 52 weeks for lower dosage. The three granules are corresponding to the three traditional Chinese syndromes in sequence, which are syndrome of deficiency of pulmono-splenic qi, syndrome of insufficiency of qi of the lung and kidney, syndrome of insufficiency of qi and yin of the lung and kidney. | Drug: Salmeterol / fluticasone (Seretide®)<br>* According to the revised 2013 GOLD, Salmeterol / fluticasone was used to severe and very severe COPD patients for 52weeks: Salmeterol / fluticasone (Seretide®, GlaxoSmithKline), 50/500 μg / dose, 60 inhalations. 50/500 μg each time, twice daily.<br>Drug: Bufeijianpi granule<br>* According to traditional Chinese syndrome differentiation and treatment, patients with syndrome of deficiency of pulmono-splenic qi will be given Bufeijianpi granule, twice daily for 52 weeks for lower dosage.<br>Drug: Bufeiyishen granule<br>* According to traditional Chinese syndrome differentiation and treatment, patients with syndrome of insufficiency of qi of the lung and kidney will be given Bufeiyishen granule, twice daily for 52 weeks for lower dosage.<br>Drug: Yiqizishen granule<br>* According to traditional Chinese syndrome differentiation and treatment, patients with syndrome of insufficiency of qi and yin of the lung and kidney will be given Yiqizishen granule granule, twice daily for 52 weeks for lower dosage.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The frequency of exacerbation |  | Change from Baseline in the frequency of exacerbation at the week13, 26, 39 and 52 of the treatment phase, the week 13, 26, 39 and 52 of the followup phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | The mortality of COPD and all-cause mortality will be calculated. | 52 Weeks of the treatment phase and the 52 Weeks of the followup phase | 
| Forced expiratory volume in one second | FEV1 is the amount of air that can be exhaled in one second. A positive change from baseline in FEV1 indicates improvement in lung function. | Change from Baseline in the one second (FEV1) at the week13, 26, 39 and 52 of the treatment phase, the week 13, 26, 39 and 52 of the followup phase. | 
| Dyspnea | Using Modified Medical Research Council ( MMRC) scale to assess a patient's level of dyspnea. The MMRC scale is a simple grading system that scored from 0 (less severe) to 4 (severe). | Change from Baseline in MMRC at the week13, 26, 39 and 52 of the treatment phase, the week 13, 26, 39 and 52 of the followup phase | 
| 6 Minutes Walking Distance Test ( 6MWD) |  | Change from Baseline in the 6MWD at the week 13, 26, 39 and 52 of the treatment phase, the week 13, 26, 39 and 52 of the followup phase. | 
| Quality of life | Using three instruments, COPD Assessment Test ( CAT) , Short Form 36-Item Health Survey (SF-36) and patient reported outcome for chronic obstructive pulmonary disease (COPD-PRO), to asses the impact of COPD on a person's life, and how this changes over time. | Change from Baseline in the CAT, SF-36 and COPD-PRO at the week 13, 26, 39 and 52 of the treatment phase, the week 13, 26, 39 and 52 of the followup phase. | 
| Effectiveness satisfaction with treatment | Using the effectiveness satisfaction questionnaire of chronic obstructive pulmonary disease (ESQ-COPD) to evaluate COPD patients' satisfaction with their treatment over time. | Change from Baseline in the ESQ-COPD at the week 13, 26, 39 and 52 of the treatment phase, the week 13, 26, 39 and 52 of the followup phase. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Disease, Chronic Obstructive, Medicine, Chinese Traditional, Humans, Treatment Outcome