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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Atrial Premature Complexes
• Intervention / Treatment: Drug: 1/2 Normal-dose Wenxin Granules; Drug: Normal-dose Wenxin Granules; Drug: Twice Normal-dose Wenxin Granules; Drug: Placebo

Detailed Description

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:

1. Low-dose Group(1/2 Normal-dose Wenxin Granules ):Wenxin Granules (no sucrose) 2.5g + Wenxin Granules placebo 7.5g.
2. Medium-dose Group(Normal-dose Wenxin Granules ):Wenxin Granules (no sucrose) 5g + Wenxin Granules placebo 5g.
3. High-dose Group(Twice Normal-dose Wenxin Granules):Wenxin Granules (no sucrose) 10g.
4. 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

1. Change in Total Score From Baseline in Traditional Chinese Medicine Syndrome Score Scale (TCMSSS).

   Time Frame: Week 0 to Week 4

2. 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

1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 Time Frame: Week 0 to Week 4
2. Impact of treatment on Liver Function Time Frame: Week 0 to Week 4
3. Impact of treatment on Renal Function Time Frame: Week 0 to Week 4
4. Impact of treatment on Hemoglobin Levels Time Frame: Week 0 to Week 4
5. Impact of treatment on White Blood Cells Time Frame: Week 0 to Week 4
6. Impact of treatment on Blood Platelet Time Frame: Week 0 to Week 4
7. Impact of treatment on Hematuria and Proteinuria Time Frame: Week 0 to Week 4

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hongli Wu; Phone Number: 8601064014411; Email: holiwu@yeah.net
• Study Contact Backup: Name: Haixia Li; Phone Number: 860108001018; Email: 2272236055@qq.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Recruiting
      • Guang'anmen Hospital, China Academy of Chinese Medical Sciences
      • Contact: Haixia Li; Phone Number: 8601088001018; Email: 2272236055@qq.com
      • Contact: Xingjiang Xiong; Phone Number: 8615801463736; Email: 5administration@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Accord with the diagnostic criteria of arrhythmia (atrial premature beats );
2. Accord with the diagnostic criteria of deficiency of both qi and yin and heart vessel stasis and obstruction Syndrome;
3. The number of premature beat of 24 h dynamic electrocardiogram >360 times/h or >8640 times/24h;
4. 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);
5. Ages 18 to 75 years old ,all genders;
6. Voluntary subjects and signed the informed consent form.

Exclusion Criteria:

1. Serious condition that need to merge other anti-arrhythmic drugs(I,II,III,IV) to treat;
2. Heart rhythm disorders caused by the factors such as drugs ,electrolyte and acid-base balance disorders;
3. Merge tardy arrhythmia (including sick sinus syndrome and II degree atrioventricular block);
4. Removed predisposing factors (such as fatigue, nervousness, mood swings, alcoholism, etc.) the premature beats reduced, while the symptoms significantly relieved;
5. Patients who have pacemaker implanted or have undergone heart percutaneous coronary intervention (PCI) surgery;
6. Patients with severe hypotension;
7. 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);
8. Allergic constitution; the test drug allergy or its ingredients or elements allergy;
9. Pregnancy and lactation women ,recent preparation pregnancy;
10. Patients with chronic alcoholism , drug dependence, mental illness;
11. Participated in other clinical trials within 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose Group; The intervention is half-dose of Wenxin Granules (1/2 normal dose).	Drug: 1/2 Normal-dose Wenxin Granules; 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.
Experimental: Medium-dose Group; The intervention is medium-dose of Wenxin Granules (normal dose).	Drug: Normal-dose Wenxin Granules; 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.
Experimental: High-dose Group; The intervention is twice-dose of Wenxin Granules (twice normal dose).	Drug: Twice Normal-dose Wenxin Granules; 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.
Placebo Comparator: Placebo Group; The intervention is a placebo.	Drug: Placebo; The drugs should be taken 10 g orally each time, 3 times a day after meals, for 4 weeks. Ingredients: Wenxin Granules placebo 10g.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Following drug administration, a review of subjective symptoms will be performed.	Week 0 to Week 4
Impact of treatment on Liver Function	Blood samples will be collected to examine the impact of treatment on the levels of ALT, AST in the subjects blood.	Week 0 to Week 4
Impact of treatment on Renal Function	Blood samples will be collected to examine the impact of treatment on the levels of Cr, Bun in the subjects blood.	Week 0 to Week 4
Impact of treatment on Hemoglobin Levels	Blood samples will be collected to examine the impact of treatment on the levels of Hemoglobin in the subjects blood.	Week 0 to Week 4
Impact of treatment on White Blood Cells	Blood samples will be collected to examine the impact of treatment on the levels of white blood count in subjects blood.	Week 0 to Week 4
Impact of treatment on Blood Platelet	Blood samples will be collected to examine the impact of treatment on the levels of Blood Platelet in subjects blood.	Week 0 to Week 4
Impact of treatment on Hematuria and Proteinuria	Urine samples will be collected to examine the the presence and amount of blood and protein in the urine.	Week 0 to Week 4

Collaborators and Investigators

• Sponsor: China Academy of Chinese Medical Sciences
• Investigators: Principal Investigator: Hongli Wu, China Academy of Chinese Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: October 29, 2019
• First Submitted That Met QC Criteria: November 12, 2019
• First Posted (Actual): November 15, 2019

Study Record Updates

• Last Update Posted (Actual): November 18, 2022
• Last Update Submitted That Met QC Criteria: November 16, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Traditional Chinese Medicine; arrhythmia; Wenxin Granules; Dose-effect relationship; Deficiency of both Qi and Yin Syndrome; Heart Vessel Stasis and Obstruction Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Cardiac Complexes, Premature; Atrial Premature Complexes
• Other Study ID Numbers: WX20150820

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No