Efficacy and Safety of Metoprolol Tartrate Tablets Combined With Chinese Traditional Medicine on Premature Ventricular Complex.

Efficacy and Safety of Metoprolol Tartrate Tablets Combined With Chinese Traditional Medicine on Premature Ventricular Complex: a Multicenter, Randomized, Double-blind, Parallel Controlled Clinical Study.

Objective: investigators investigated the effects of metoprolol tartrate plus Tongmai Yangxin Pill on premature ventricular complexes and cardiac function in patients with premature ventricular complex.

Methods: In total, 584 participants with premature ventricular complex will be randomly assigned (at a 1:1 ratio) into two groups: study group (metoprolol tartrate [25 mg twice per day, orally] plus Tongmai Yangxin Pill [40 pills twice per day, orally]) and control group (metoprolol tartrate [25 mg twice per day, orally] plus placebo [40 simulated pills twice per day, orally]). The total treatment period is 8 weeks.

Efficacy endpoints and safety assessment:

Primary efficacy endpoints are as follows: change in 24-h number of PVCs after treatment and effective rate of 24-h number of PVCs after treatment. Secondary efficacy endpoints are as follows: change in New York Heart Association classification; total effective rate of comprehensive effect; change in high-sensitivity C-reactive protein level; and change in echocardiography parameters (i.e., left ventricular ejection fraction, left ventricular end diastolic dimension, E/A, cardiac index, cardiac output, and stroke volume).

Study Overview

• Status: Completed
• Conditions: Premature Ventricular Contraction
• Intervention / Treatment: Drug: Tongmai Yangxin Pill (TMYXP); Drug: metoprolol tartrate; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 584
• Phase: Phase 4

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:

• Lown PVC grade, II-IVA;
• in patients with coronary heart disease and comorbid PVC or non-organic heart disease, the PVC frequency was 3000-30000 times/24 h;
• New York Heart Association grade, I or II;
• ejection fraction, ≥45%;
• written informed consent to participate in the trial.

Exclusion Criteria:

• presence of bradyarrhythmia (<50 beats/min), including sinus syndrome and atrioventricular block (second or third degree atrioventricular block);
• presence of persistent ventricular tachycardia, non-persistent ventricular tachycardia, and/or persistent atrial fibrillation;
• presence of severe PVC requiring treatment with other antiarrhythmic drugs; -presence of drug-induced, electrolyte-induced, or acid-base-induced arrhythmia;
• presence of uncontrolled or severe hypertension (e.g., grade ≥3 hypertension);
• presence of uncontrolled diabetes; presence of alanine aminotransferase or aspartate aminotransferase level ≥1.5-fold above the upper limit of normal, urea nitrogen level ≥1.2-fold above the upper limit of normal, and/or blood creatinine above the upper limit of normal;
• presence of severe respiratory dysfunction or asthma;
• presence of primary hematopoietic diseases, other systemic diseases (e.g., hyperthyroidism), poor peripheral circulation perfusion, severe peripheral vascular diseases, and/or PVC with unknown etiology;
• presence of allergic constitution, mental disorder, alcoholism, and/or smoking habit;
• pregnancy or lactation;
• ongoing β-blocker treatment or contraindications to β-blocker treatment; -participation in other clinical trials within the prior 3 months;
• and other reasons for lack of suitability to participate in this study, as determined by the investigators.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: study group; Metoprolol tartrate (25 mg twice per day, orally) plus TMYXP (40 pills twice per day, orally). the treatment duration is 8 weeks.	Drug: Tongmai Yangxin Pill (TMYXP); TMYXP is a Chinese patent medicine developed by many years of clinical practice experience. The ingredients of TMYXP are Radix Rehmanniae, Caulis Spatholobi, Polygonum Multiflorum, Colla Corii Asini, Ophiopogonis, Tortoise Shell (vinegar), Radix Codonopsis, Cassia Twig, Jujube, Schisandra Fruit, and Licorice Root. It has the effect of invigorating Qi, nourishing Yin, dredging the pulse, and relieving pain. It is used in treatment of Qi and Yin deficiency syndromes caused by coronary heart disease, angina pectoris, and arrhythmia. Metoprolol tartrate (a heart-selective β-blocker) is a class II antiarrhythmic medication that decreases the ventricular rate of supraventricular tachyarrhythmias by inhibition of atrioventricular conduction.; Drug: metoprolol tartrate; metoprolol tartrate (a heart-selective β-blocker) is a class II antiarrhythmic medication that decreases the ventricular rate of supraventricular tachyarrhythmias by inhibition of atrioventricular conduction.; Other Names: metoprolol; betaloc
Placebo Comparator: control group; Metoprolol tartrate (25 mg twice per day, orally) plus placebo (40 simulated pills twice per day, orally). The treatment is 8 weeks.	Drug: metoprolol tartrate; metoprolol tartrate (a heart-selective β-blocker) is a class II antiarrhythmic medication that decreases the ventricular rate of supraventricular tachyarrhythmias by inhibition of atrioventricular conduction.; Other Names: metoprolol; betaloc; Drug: placebo; simulated pills

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 24-h number of PVCs after 8-week treatment		8 weeks
Effective rate of 24-h number of PVCs after 8-week treatment.	the definition of "effective" is, premature ventricular complex decreased by 50%-70% compared with baseline in the Holter result.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in New York Heart Association (NYHA) classification	Marked effective NYHA improvement was defined as reduction of NYHA grade by ≥2; effective NYHA improvement was defined as reduction of NYHA grade by 1; non-effective NYHA improvement was defined as no change or elevation of NYHA grade.	8 weeks
total effective rate of comprehensive effect	Total effective rate of comprehensive effect was defined as total symptom score; clinical recovery was defined as significant improvement of clinical symptoms and reduction of symptom score by ≥90%.	8 weeks
change in high-sensitivity C-reactive protein level		8 weeks
change in echocardiography parameter left ventricular ejection fraction		8 weeks
change in echocardiography parameter left ventricular end diastolic dimension		8 weeks
change in echocardiography parameter E/A		8 weeks
change in echocardiography parameter cardiac index		8 weeks
change in echocardiography parameter cardiac output		8 weeks
change in echocardiography parameter stroke volume		8 weeks

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Collaborators: Tianjin Lerentang factory
• Investigators: Principal Investigator: Qi Hua, PhD, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: July 25, 2021
• First Submitted That Met QC Criteria: August 9, 2021
• First Posted (Actual): August 17, 2021

Study Record Updates

• Last Update Posted (Actual): August 17, 2021
• Last Update Submitted That Met QC Criteria: August 9, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Cardiac Complexes, Premature; Premature Birth; Ventricular Premature Complexes; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Metoprolol
• Other Study ID Numbers: 2013019

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