Evaluating the Safety and Efficacy of Qishen Granules Among Patients With Chronic Heart Failure

Study Overview
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Brief Summary
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This trial will assess the efficacy and safety of QSG in CHF.

Detailed Description
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Background: Chronic heart failure(CHF), the final stage of various cardiovascular diseases, is a major public health problem associated with significant hospitalization rates, mortality, and huge health care costs, despite advances in the treatment and management of heart failure and heart failure related risk factors. Qishen granules(QSG), a Chinese herbal formula, is widely used by traditional chinese medicine(TCM) practitioners to treat CHF. Several animal experimental studies have showed that QSG can significantly relieve the heart failure symptoms of CHF rat models. However, there is yet no standard clinical trial to assess that. Thus, the investigators are conducting this study to evaluate the efficacy and safety of QSG in a large, varied population. Methods/Design: This study is designed as a randomized, multi-center, placebo-controlled, double-blind , parallel-group clinical trial. An established total of 200 patients with CHF will be recruited and randomly allocated to either the QSG treatment group or the placebo group (a 1:1 ratio). The patients will receive QSG or placebo granules twice daily for 12 weeks. The primary endpoint is the reduction or percent change in the plasma N-terminal pro-B-type natriuretic peptide(NT-proBNP) level during 12 weeks of treatment. The secondary endpoints consist of composite cardiac events (CCEs), New York Heart Association (NYHA) functional classification, 6-minute walking distance (6MWD), Left ventricular ejection fraction, patient quality of life and TCM syndrome integral scale. Discussion: This trial will assess the efficacy and safety of QSG in CHF.

Official Title
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Evaluating the Safety and Efficacy of Qishen Granules Among Patients With Chronic Heart Failure: Study Protocol for a Randomized Controlled Trial

Conditions
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Heart Failure, Cardiovascular Diseases

Intervention / Treatment
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* Drug: Qishen Granules
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age between 18 and 75 years; clinical findings of CHF for at least 3 months prior to screening; CHF caused by coronary heart disease and hypertension, which is diagnosed according to the Chinese guidelines published in 2014 for the diagnosis and management of CHF; clinically stable condition with an NYHA functional class of II to III and an optimal medical treatment with a fixed dosage for at least 2 weeks; a documented left ventricular ejection fraction (LVEF) ≤40% and a serum NT-proBNP level ≥450 pg/ml; CHF of Qi deficiency and blood stasis syndrome; provision of written informed consent. Exclusion Criteria: CHF complicated with severe valvular disease, congenital heart disease, pericardial disease, cardiomyopathy, unstable angina, acute myocardial infarction(in recent 4 weeks), cardiogenic shock, acute myocarditis, infective endocarditis, uncontrolled severe cardiac arrhythmia with hemodynamic changes; pulmonary heart disease, pulmonary hypertension caused by acute or chronic pulmonary embolism or cerebral apoplexy in recent 6 months; severe hepatic inadequacy with alanine aminotransferase or alkaline phosphatase levels >2 times the upper normal limit, renal inadequacy with a creatinine clearance rate>20% or a serum creatinine level>3mg/dl (>265μmol/L), severe electrolyte imbalance, severe hematologic disease, malignant tumor, diabetes mellitus with severe complications, or severe endocrine diseases such as hyperthyroidism and hypothyroidism; acute infection confirmed by any one of the following 3 tips: 1) fever; 2) a white blood cell count>10×109/L and a percentage of neutrophils>85%; 3) shadows on chest X-ray; uncontrolled blood pressure or fibrosis in other organs; CHF of yin deficiency according to TCM syndrome differentiation; pregnancy or breastfeeding; psychiatric or infectious disease; patients who have participated in other clinical trials in the past two months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Qishen granules<br>The QSG treatment group will receive Qishen granules (13.6 g/pouch, twice per day-30 minutes after breakfast and dinner-for 12 weeks; dosage based on the requirements of Pharmacopoeia of the People's Republic of China). | Drug: Qishen Granules<br>* The QSG are manufactured by Beijing tcmages Pharmaceutical Co., Ltd. (Beijing, China), a company that has obtained Chinese Good Manufacturing Practice for Pharmaceutical Products certification. All the ingredients have been approved by the Chinese Ministry of Food and Drug Safety. 13.6 grams (dry weight) of granules consist of six herbs: Astragalus membranaceus (Fisch.) Bge. var. Mongolicus (Bge.) Hsiao (6g), Salvia miltiorrhiza Bge. (1.5g), Lonicera japonica Thunb. (2g), Scrophularia ningpoensis Hemsl. (2g), Aconitum carmichaeli Debx. (0.9g), and Glycyrrhiza uralensis Fisch. (1.2g).<br>* Other names: Yixin Jiedu formula;|
| Placebo Comparator: placebo granules<br>The placebo group will receive placebo granules (13.6 g/pouch, twice per day-30 minutes after breakfast and dinner-for 12 weeks). | Drug: Placebo<br>* The placebo is manufactured by Beijing tcmages Pharmaceutical Co., Ltd. (Beijing, China) as well, following the Specification for processing Chinese medicine in Beijing. The placebo granules are similar in appearance, taste, and scent to the Qishen granules.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the reduction or percent change in the plasma N-terminal pro-B-type natriuretic peptide |  | 12weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| composite cardiac events |  | 4weeks,8weeks,12weeks | 
| New York Heart Association (NYHA) functional classification |  | 4weeks,8weeks,12weeks | 
| 6-minute walking distance |  | 4weeks,8weeks,12weeks | 
| Left ventricular ejection fraction |  | 12weeks | 
| Chronic Heart Failure Quality of Life Scale of Integrated Chinese and Western Medicine |  | 4weeks,8weeks,12weeks | 
| TCM syndrome integral scale |  | 4weeks,8weeks,12weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic heart failure, traditional Chinese medicine, Qishen granules