Effect of Yong Chong Cao Capsule on Outcomes in Patients With Mild to Severe COPD

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effectiveness of Yong Chong Cao capsule on outcomes in patients with mild to severe Chronic Obstructive Pulmonary Disease (COPD).

Detailed Description
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The aim of this study is to compare the effectiveness of two treatments for mild to severe COPD patients: one, Yong Chong Cao capsule treatment and conventional medicine based on 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Chinese Treatment Guidelines; the other, Bailing capsule treatment and conventional medicine. COPD, with high prevalence, morbidity, mortality and economic burdens, affects millions worldwide. Although many therapies exist and are being developed to relieve symptoms and reduce mortality in COPD, most have only been studied in placebo-controlled efficacy studies in highly selected populations. There are few clinical trials to compare therapeutic alternatives in real world. Furthermore, some randomized controlled trials on Yong Chong Cao capsule, one therapeutic type of Cordyceps sinensis in traditional Chinese medicine (TCM) interventions, especially based on the syndrome of insufficiency of qi of the lung and kidney patterns, have been the certain evidence for showing definite effect for COPD patients. In addition, studies in real world populations of COPD that received different cordyceps sinensis therapies that do have efficacy evidence was found wide variations in care delivery. In short, there is a need to compare the effectiveness of two capsule in patients with mild to severe COPD. This is a multi-center, open-label, randomized, controlled study to evaluate the effectiveness of Yong Chong Cao capsule for patients with mild to severe COPD compared with Bailing capsule. Following a 14 day run-in period, approximately 240 subjects will be randomly assigned to Yong Chong Cao capsule treatment group, Bailing capsule treatment group for 24 weeks. After the 24 weeks treatment period, subjects in two treatments arms will follow-up 24 weeks. The primary outcome measure is the frequency of exacerbations. The secondary efficacy measures include FEV1, dyspnea (MMRC), exercise capacity(6MWD), quality of life (CAT, SGRQ). Safety will be assessed through the collection of adverse events. There will be a total of 4 study visits (baseline, the 12 and 24 weeks of the treatment, the 24 weeks of follow-up).

Official Title
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A Multi-center, Open-label, Randomized, Controlled Study to Evaluate the Effectiveness of Yong Chong Cao Capsule on Outcomes in Patients With Mild to Severe COPD

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Salbutamol (Ventolin®)
* Drug: Tiotropium Bromide (Spiriva®)
* Drug: Salmeterol / fluticasone (Seretide®)
* Drug: YCC capsule
* Drug: BL capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A confirmed diagnosis of mild to severe COPD. Medically stable. Syndrome differentiation belongs to syndrome of insufficiency of qi of the lung and kidney. Age between 18 and 80 years. With the informed consent signed. Exclusion Criteria: Pregnant or breast-feeding women. Current respiratory disorders other than COPD (e.g., bronchiectasis, bronchial asthma, tuberculosis, lung fibrosis, pulmonary thromboembolic, diffuse panbronchiolitis, lung cancer). Complicated with heart failure (NYHA Class III or IV), or myocardial infarction within six months ,or unstable hemodynamics. Complicated with serious hepatic and renal diseases (liver cirrhosis, portal hypertension, bleeding of varicose veins, dialysis, or renal transplantation). Any psychiatric condition rendering the patient unable to understand the nature, scope and possible consequences of the study. Participating in other trials or allergic to the used medicine. Participating in other clinical trials with other interventions in one month. Allergic to the used medicine.

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YCC capsule+conventional medicine<br>Patients in this group will be given Yong Chong Cao (YCC) capsule and conventional medicine based on the classes of medications recommended by 2017 GOLD and Chinese Treatment Guidelines for COPD,which are Group A patients: Salbutamol (Ventolin®),Group B and Group C patients: Tiotropium Bromide (Spiriva®),Group D patients: Salmeterol / fluticasone (Seretide®). | Drug: Salbutamol (Ventolin®)<br>* According to the revised 2017 GOLD, patients will be divided into Group A, B, C, and D based on individualized assessment. Salbutamol will be used to Group A patients: Salbutamol (Ventolin®, GlaxoSmithKline) 100μg/dose. 100 μg each time (when needed), and the maximum dose is 8-12 inhalations a day.<br>* Other names: Group A patients: Salbutamol (Ventolin®).;Drug: Tiotropium Bromide (Spiriva®)<br>* Tiotropium Bromide Powder for Inhalation will be used to Group B and Group C patients: Tiotropium Bromide Powder for Inhalation(Spiriva®, Boehringer Ingelheim), 18μg/ capsule, 10 capsules. 18μg each time, once daily.<br>* Other names: Group B and C patients: Tiotropium Bromide (Spiriva®);Drug: Salmeterol / fluticasone (Seretide®)<br>* Salmeterol / fluticasone will be used to Group D patients: Salmeterol / fluticasone (Seretide®, GlaxoSmithKline), 50/250 μg / dose, 60 inhalations. 50/250 μg each time, twice daily.<br>* Other names: Group D patients: Salmeterol / fluticasone (Seretide®);Drug: YCC capsule<br>* According to traditional Chinese syndrome differentiation and treatment, patients with syndrome of insufficiency of qi of the lung and kidney will be given Yong Chong Cao (YCC)capsule (Kecai®, Guangdong daguang pharmaceutical group Co., Ltd), 1 g each time, three times a day.<br>|
| Experimental: BL capsule + conventional medicine<br>Patients in this group will be given Bailing (BL) capsule and conventional medicine based on the classes of medications recommended by 2017 GOLD and Chinese Treatment Guidelines for COPD, which are Group A patients: Salbutamol (Ventolin®),Group B and Group C patients: Tiotropium Bromide (Spiriva®),Group D patients: Salmeterol / fluticasone (Seretide®). | Drug: Salbutamol (Ventolin®)<br>* According to the revised 2017 GOLD, patients will be divided into Group A, B, C, and D based on individualized assessment. Salbutamol will be used to Group A patients: Salbutamol (Ventolin®, GlaxoSmithKline) 100μg/dose. 100 μg each time (when needed), and the maximum dose is 8-12 inhalations a day.<br>* Other names: Group A patients: Salbutamol (Ventolin®).;Drug: Tiotropium Bromide (Spiriva®)<br>* Tiotropium Bromide Powder for Inhalation will be used to Group B and Group C patients: Tiotropium Bromide Powder for Inhalation(Spiriva®, Boehringer Ingelheim), 18μg/ capsule, 10 capsules. 18μg each time, once daily.<br>* Other names: Group B and C patients: Tiotropium Bromide (Spiriva®);Drug: Salmeterol / fluticasone (Seretide®)<br>* Salmeterol / fluticasone will be used to Group D patients: Salmeterol / fluticasone (Seretide®, GlaxoSmithKline), 50/250 μg / dose, 60 inhalations. 50/250 μg each time, twice daily.<br>* Other names: Group D patients: Salmeterol / fluticasone (Seretide®);Drug: BL capsule<br>* According to traditional Chinese syndrome differentiation and treatment, patients with syndrome of insufficiency of qi of the lung and kidney will be given Bailing(BL) capsule (Bailing®, Huadong Medicine Co.,Ltd), 1 g each time, three times a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The frequency of exacerbation of COPD | The exacerbation of COPD often results in reduced quality of life, increased rate of lung function decline, increased hospitalization. It is important to assess the changes of exacerbations over time. | Changes in the frequency of exacerbation at the week 12 and week 24 of the treatment phase, and at the week 24 of the follow-up phase compared with baseline. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Modified Medical Research Council scale scores | 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). | Changes in the mMRC scores at the week 12 and week 24 of the treatment phase, and the week 24 of the follow-up phase compared with baseline. | 
| Changes in Forced expiratory volume in one second | 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. | Changes in FEV1 at the week 24 of the treatment phase and the week 24 of the follow-up phase compared with baseline. | 
| Changes in COPD Assessment Test scores | Using the COPD Assessment Test ( CAT) , to assess the impact of COPD on a person's symptom, and how this changes over time. | Changes in the CAT scores at the week 12 and week 24 of the treatment phase, and the week 24 of the follow-up phase compared with baseline. | 
| Changes in Six Minutes Walking Distance | Using the results of six Minutes Walking Distance (6MWD)Test to assess the exercise tolerance. | Changes in the 6WMD scores at the week 12 and week 24 of the treatment phase, and the week 24 of the follow-up phase compared with baseline. | 
| Changes in St Georges respiratory questionnaire scores | Using the St. George's Respiratory Questionnaire(SGRQ), to assess the impact of COPD on a person's life, and how this changes over time. | Changes in the SGRQ scores at the week 12 and week 24 of the treatment phase, and the week 24 of the follow-up phase compared with baseline. | 
| Changes in clinical COPD questionnaire scores | Using the clinical COPD questionnaire (CCQ), to assess the impact of COPD on a person's life, and how this changes over time. | Changes in the CCQ scores at the week 12 and week 24 of the treatment phase, and the week 24 of the follow-up phase compared with baseline. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Disease, Chronic Obstructive, mild, moderate, severe, Medicine, Chinese Traditional, Cordyceps sinensis