Efficacy and Safety of Qishenyiqi Dripping Pills for Treating Chronic Heart Failure With Reduced Ejection Fraction (Syndrome of Qi Deficiency and Blood Stasis) Due to Coronary Heart Disease

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety and the best effective dose of Qishen Yiqi Drop Pills in the treatment of chronic heart failure with decreased ejection fraction of CHD (Qi deficiency and blood stasis syndrome).

Official Title
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A Multi-center, Randomized, Double-blind, Placebo-parallel Controlled, Standardise-loaded Ⅱ Clinical Trial of Efficacy and Safety of Qishenyiqi Dripping Pills for Treating Chronic Heart Failure With Reduced Ejection Fraction (Syndrome of Qi Deficiency and Blood Stasis) Due to Coronary Heart Disease

Conditions
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Chronic Heart Failure With Reduced Ejection Fraction

Intervention / Treatment
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* Drug: Low dose Qishenyiqi Dripping Pills 3 bags
* Drug: High dose Qishenyiqi Dripping Pills 3 bags
* Drug: Qishenyiqi Dripping Pills placebo 3 bags


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Conformed to the diagnostic criteria of CHD and chronic heart failure Conformed to the TCM syndrome differentiation standard of chronic heart failure syndrome of Qi deficiency and blood stasis Male or female subjects aged ≥ 40 years and ≤80 years LVEF<45%(modified Simpson method) NYHAⅡ-Ⅲ Received standardized drug therapy for chronic heart failure at least 2 weeks before randomization, and did not receive intravenous therapy (vasoactive drugs, diuretics) within 2 weeks without adjustment of dose Ability to understand the requirements of the study and willingness to provide written informed consent Have no pregnancy program and take effective contraceptive measures voluntarily Abide by the experimental protocol and cooperate with the data collection according to the researcher's judgment Exclusion Criteria: Patients with heart failure caused by other heart diseases,such as cor pulmonale, congenital heart disease, primary pulmonary hypertension, secondary severe pulmonary hypertension, severe stenosis or insufficiency of heart valves, cardiomyopathy (including hypertrophic cardiomyopathy, restrictive cardiomyopathy, dilated cardiomyopathy, alcoholic cardiomyopathy), moderate massive pericardial effusion, constrictive pericarditis, infective endocarditis Heart failure caused by systemic diseases or other systemic diseases, such as rheumatic immune and secretory diseases;heart failure caused by kidney disease, lung disease, liver disease and serious infection;heart failure caused by chemical or toxicological causes Patients who had acute myocardial infarction, underwent coronary revascularization or left ventricular remodeling, underwent cardiac resynchronization with pacemaker implantation, underwent cardiothoracic surgery within 3 months prior to receiving the experimental drug, patients with other acute coronary syndrome, pulmonary embolism or acute cerebrovascular disease Severe arrhythmias such as ventricular tachycardia, second degree Ⅱ type or above sinus atrial or atrioventricular block without pacemaker treatment, average QTc > 500ms, heart rate < 50 beats/min, etc Complicated with other serious diseases, such as pheochromocytoma, hematologic diseases, organ transplantation patients, and any history of malignant tumor The presence of uncontrolled hypertension, systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg Hypotension with a systolic blood pressure <80mmHg and/or a diastolic blood pressure <50mmHg Patients with hepatic and/or renal dysfunction (ALT≥ 2 times the upper limit of normal, and/or estimated glomerular filtration rate (EGFR) <30 mL /min/1.73m2 HbA1c ≥9.0%, or fasting blood glucose ≥13.9mmol/L Moderate and severe anemia (Hb < 90g/L) Serum potassium ≥5.5mmol/L Patients requiring anticoagulants who did not achieve dose stabilization for 1 month or INR > 3.0 In patients who need to take antiplatelet drugs, the dose was stable for less than 1 month, and the platelet value was lower than the lower limit of normal value Allergic to the test drug or its related taste or ingredients People with complicated mental illness, poor condition control and drug addiction Unable to complete 6MWT Pregnant or lactating women Participation in other studies and use of investigational drugs from other studies within 3 months prior to screening The investigator deems that the patient is not suitable to participate in the study, including the investigator's judgment that the patient is unable to complete the study or comply with the requirements of the study

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: Low dose group<br>Low dose Qishenyiqi Dripping Pills, 3 bags, take orally after meals, 3 times a day | Drug: Low dose Qishenyiqi Dripping Pills 3 bags<br>* Low dose Qishenyiqi Dripping Pills contain Qishenyiqi dripping pills 2 bags(0.52g dripping pills per bag) and Qishenyiqi dripping pills placebo 1 bag(0.52g dripping pills placebo per bag),take orally after meals, 3 times a day for 12weeks<br>* Other names: Low dose group;|
| Experimental: High dose group<br>High dose Qishenyiqi Dripping Pills, 3 bags, take orally after meals, 3 times a day | Drug: High dose Qishenyiqi Dripping Pills 3 bags<br>* High dose Qishenyiqi Dripping Pills contain Qishenyiqi dripping pills 3 bags(0.52g dripping pills per bag),take orally after meals, 3 times a day for 12weeks<br>* Other names: High dose group;|
| Placebo Comparator: Placebo group<br>Qishenyiqi Dripping Pills placebo, 3 bags, take orally after meals, 3 times a day | Drug: Qishenyiqi Dripping Pills placebo 3 bags<br>* Qishenyiqi Dripping Pills placebo contain Qishenyiqi dripping pills placebo 3 bags(0.52g dripping pills placebo per bag),take orally after meals, 3 times a day for 12weeks<br>* Other names: Placebo group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-Minutes-Walking-Test (6MWT) in week 12 | Change from baseline to weeks 12 in exercise capacity as measured by the 6-Minutes-Walking-Test (6MWT) distance. | Baseline to weeks 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-Minutes-Walking-Test (6MWT) in weeks 4 and 8 | Change from baseline to weeks 4 and 8 in exercise capacity as measured by the 6-Minutes-Walking-Test (6MWT) distance. | Baseline to weeks 4 and 8 | 
| NYHA classification | Percentage of subjects whose NYHA classification improved/worsened/remained unchanged from baseline to weeks 4,8 and 12. | Baseline to weeks 4,8 and 12 | 
| Traditional Chinese Medicine Syndrome Score | Change from baseline to weeks 4,8 and 12 in Traditional Chinese Medicine Syndrome Score. There were 3 clinical primary symptoms, 4 clinical secondary symptoms, tongue picture and pulse condition evaluated as TCM symptoms, which was defined as TCM syndrome score. The standard of TCM primary symptoms scored as without 0, light 2, medium 4, heavy 6 points. The standard of TCM secondary symptoms scored as without 0, with 1 points. Tongue picture and pulse condition did not count. | Baseline to weeks 4,8 and 12 | 
| Dyspnea, weakness, edema | Symptom disappearance rate(dyspnea, weakness, edema) from baseline to weeks 4,8 and 12. | Baseline to weeks 4,8 and 12 | 
| Echocardiogram results | Change from baseline to weeks 4,8 and 12 in left ventricular end diastolic diameter(LVEDD) measured by echocardiography; Change from baseline to weeks 4,8 and 12 in left ventricular end diastolic volume(LVEDV) measured by echocardiography; Change from baseline to weeks 4,8 and 12 in left ventricular end systolic volume(LVESV) measured by echocardiography; Change from baseline to weeks 4,8 and 12 in left ventricular ejection fraction(LVEF) measured by echocardiography; Change from baseline to weeks 4,8 and 12 in stroke volume(SV) measured by echocardiography; Change from baseline to weeks 4,8 and 12 in cardiac output(CO) measured by echocardiography. | Baseline to weeks 4,8 and 12 | 
| NT-proBNP | Change from baseline to weeks 4,8 and 12 in NT-proBNP. | Baseline to weeks 4,8 and 12 | 
| Minnesota Living With Heart Failure Questionnaire(MLHFQ) | Change from baseline to weeks 4,8 and 12 in Minnesota Living With Heart Failure Questionnaire(MLHFQ). The MLHFQ is a self-administered questionnaire for patients with HF, comprising 21 items representing different degrees of impact of HF on health-related quality of life. Every item in this questionnaire scores from 0 (none) to 5 (very much) and the total items score from 0 (none) to 105 (very much). | Baseline to weeks 4,8 and 12 | 
| Cardiovascular adverse events | To determine whether the incidence of cardiovascular adverse events during the study period was superior to placebo. | Week 12 |