The Dose-Effect Relationship of Wenxin Granules in the Treatment of Atrial Premature Beats

Study Overview
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Brief Summary
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A Randomized, double-blind, placebo-controlled, four dose groups, post-marketing clinical trial, to evaluate the efficacy and safety of Wenxin granules in treating atrial premature beats by different doses,to provide a scientific basis for rational clinical use of drug.

Detailed Description
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Research purpose: To evaluate the efficacy and safety of Wenxin granules in treating atrial premature beats by different doses, to provide a scientific basis for rational clinical use of drug. Research design: A Randomized, double-blind, placebo-controlled, four dose groups, post-marketing clinical trial. Sample size: The ratio of high, medium and low dose groups and placebo group were 1:1:1:1. A total of 60 cases were included in the first phase.The maximum sample size required was determined to be 150 cases. Therapeutic schedule: Low-dose Group(1/2 Normal-dose Wenxin Granules ):Wenxin Granules (no sucrose) 2.5g + Wenxin Granules placebo 7.5g. Medium-dose Group(Normal-dose Wenxin Granules ):Wenxin Granules (no sucrose) 5g + Wenxin Granules placebo 5g. High-dose Group(Twice Normal-dose Wenxin Granules):Wenxin Granules (no sucrose) 10g. Placebo Group(Placebo):Wenxin Granules placebo 10g. Usage and Dosage:The drugs should be taken 10 g orally each time, 3 times a day after meals, for 4 weeks. Drug combination: During the test should not merge the other anti-arrhythmic drugs beyond the provisions of this scheme. Due to merger disease or condition changes ,have to use drugs or other treatment, investigators must record the types (or other treatment ),drug usage, time and reasons, in order to summarize ,analyze and report. Primary Outcome Measures 1. Responder rate based on 24-hour Holter monitoring, defined as the proportion (%) of subjects with a ≥ 50% reduction in atrial premature beats during 24-hour Holter monitoring from baseline. Time Frame: Week 0 to Week 4 Secondary Outcome Measures Change in Total Score From Baseline in Traditional Chinese Medicine Syndrome Score Scale (TCMSSS). Time Frame: Week 0 to Week 4 Responder rate based on each symptom score, defined as the proportion (%) of subjects with a ≥ 1 score reduction in each symptom score from baseline. Time Frame: Week 0 to Week 4 Other Outcome Measures Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 Time Frame: Week 0 to Week 4 Impact of treatment on Liver Function Time Frame: Week 0 to Week 4 Impact of treatment on Renal Function Time Frame: Week 0 to Week 4 Impact of treatment on Hemoglobin Levels Time Frame: Week 0 to Week 4 Impact of treatment on White Blood Cells Time Frame: Week 0 to Week 4 Impact of treatment on Blood Platelet Time Frame: Week 0 to Week 4 Impact of treatment on Hematuria and Proteinuria Time Frame: Week 0 to Week 4

Official Title
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The Dose-Effect Relationship of Wenxin Granules in the Treatment of Atrial Premature Beats of Deficiency of Both Qi and Yin and Heart Vessel Stasis and Obstruction Syndrome : A Randomized, Double-blind, Placebo-controlled Clinical Trial Study

Conditions
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Atrial Premature Complexes

Intervention / Treatment
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* Drug: Normal-dose Wenxin Granules
* Drug: 1/2 Normal-dose Wenxin Granules
* Drug: Twice Normal-dose Wenxin Granules
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Accord with the diagnostic criteria of arrhythmia (atrial premature beats ); Accord with the diagnostic criteria of deficiency of both qi and yin and heart vessel stasis and obstruction Syndrome; The number of premature beat of 24 h dynamic electrocardiogram >360 times/h or >8640 times/24h; Stop using the anti- arrhythmic drugs for more than five half-life (except that who long-term (one month or more) with beta blockers for high blood pressure and exertional angina); Ages 18 to 75 years old ,all genders; Voluntary subjects and signed the informed consent form. Exclusion Criteria: Serious condition that need to merge other anti-arrhythmic drugs(I,II,III,IV) to treat; Heart rhythm disorders caused by the factors such as drugs ,electrolyte and acid-base balance disorders; Merge tardy arrhythmia (including sick sinus syndrome and II degree atrioventricular block); Removed predisposing factors (such as fatigue, nervousness, mood swings, alcoholism, etc.) the premature beats reduced, while the symptoms significantly relieved; Patients who have pacemaker implanted or have undergone heart percutaneous coronary intervention (PCI) surgery; Patients with severe hypotension; Patients with serious cardiovascular diseases (such as congestive heart failure, cardiac shock, etc.), cerebrovascular disease, and serious primary 8.diseases such as liver, kidney and hematopoietic system (ALT,AST,BUN 2 times higher than normal ceiling, or Cr higher than the upper limit of normal); Allergic constitution; the test drug allergy or its ingredients or elements allergy; Pregnancy and lactation women ,recent preparation pregnancy; Patients with chronic alcoholism , drug dependence, mental illness; Participated in other clinical trials within 3 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
Interventional Model Description: The ratio of high, medium and low dose group and placebo groups are 1:1:1:1. A total of 60 cases are included in the first phase.The maximum sample size required is determined to be 150 cases.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose Group<br>The intervention is half-dose of Wenxin Granules (1/2 normal dose). | Drug: 1/2 Normal-dose Wenxin Granules<br>* The drugs should be taken 10 g orally each time, 3 times a day after meals, for 4 weeks. Ingredients: Wenxin Granules (no sucrose) 2.5g + Wenxin Granules placebo 7.5g.<br>|
| Experimental: Medium-dose Group<br>The intervention is medium-dose of Wenxin Granules (normal dose). | Drug: Normal-dose Wenxin Granules<br>* The drugs should be taken 10 g orally each time, 3 times a day after meals, for 4 weeks. Ingredients: Wenxin Granules (no sucrose) 5g + Wenxin Granules placebo 5g.<br>|
| Experimental: High-dose Group<br>The intervention is twice-dose of Wenxin Granules (twice normal dose). | Drug: Twice Normal-dose Wenxin Granules<br>* The drugs should be taken 10 g orally each time, 3 times a day after meals, for 4 weeks. Ingredients: Wenxin Granules (no sucrose) 10g.<br>|
| Placebo Comparator: Placebo Group<br>The intervention is a placebo. | Drug: Placebo<br>* The drugs should be taken 10 g orally each time, 3 times a day after meals, for 4 weeks. Ingredients: Wenxin Granules placebo 10g.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rate based on 24-hour Holter monitoring. | Defined as the proportion (%) of subjects with a ≥ 50% reduction in atrial premature beats during 24-hour Holter monitoring from baseline. | Week 0 to Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Score From Baseline in Traditional Chinese Medicine Syndrome Score Scale. | The rating scale consisted of 12 items (1 for the main symptoms and 11 for the accompanying symptoms) with 4 options (absent, mild, moderate or severe) for each item. Each option was represented by a fixed score(0,1,2,3), the higher the score, the more severe the symptom, and vice versa. The total score of the rating scale was called syndrome integral. Symptoms include palpitation, chest distress, chest pain, shortness of breath, lack of strength, insomnia, dreamfulness, dizziness, dim complexion, vexing heat in chest, palms and soles, dry mouth, cyanotic lips and nails. The changes of TCM syndrome scores before and after treatment were compared. | Week 0 to Week 4 | 
| Responder rate(%) based on each symptom score. | Defined as the proportion (%) of subjects with a ≥ 1 score reduction in each symptom score from baseline. | Week 0 to Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Wenxin Granules, Dose-effect relationship, Deficiency of both Qi and Yin Syndrome, Heart Vessel Stasis and Obstruction Syndrome, Traditional Chinese Medicine, arrhythmia