Effectiveness and safety of Guipi Mixture for the treatment of premature ventricular contractions (heart-spleen deficiency syndrome): study protocol for a randomized, double-blind, placebo-controlled, multicentre trial

INTRODUCTION: Premature ventricular contractions (PVCs) are a common arrhythmia. Long‐term frequent PVCs may contribute to tachycardia‐induced cardiomyopathy, exacerbate angina, or trigger more severe ventricular arrhythmias, increasing cardiovascular risk. Current Western guidelines recommend pharmacotherapy or catheter ablation, with conservative drug therapy (e.g., lidocaine, propafenone, metoprolol, amiodarone, verapamil) remaining the mainstay. Metoprolol tartrate, a first‐line drug, is effective for PVCs but has single targets, limited efficacy, and potential long‐term cardiovascular adverse effects. Traditional Chinese Medicine (TCM) offers high efficacy and low toxicity. Guipi Mixture, a Chinese patent medicine for heart‐spleen deficiency syndrome, combined with Western medicine may overcome these limitations. This study evaluates the efficacy and safety of Guipi Mixture plus metoprolol for PVCs (heart‐spleen deficiency syndrome). METHODS: This is a randomized, double‐blind, placebo‐controlled, multicenter trial. Across 18 centers, 200 eligible subjects will be randomized (1:1) to intervention (Guipi Mixture + metoprolol) or control (Guipi Mixture placebo + metoprolol). The 12‐week trial includes a 2‐week screening, 2‐week run‐in, and 8‐week treatment period. The primary outcome is the absolute change in 24 h PVC count from baseline to week 8 measured by ambulatory ECG (AECG). Secondary outcomes include responder rate (based on PVC reduction), SF‐36 quality of life, PSQI sleep quality, TCM syndrome score, and ECG indicators. Adverse events will be recorded throughout the trial. DISCUSSION: This study will provide evidence on the efficacy and safety of Guipi Mixture for PVCs (heart‐spleen deficiency syndrome) and explore its impact on patients' quality of life. CLINICAL TRIAL REGISTRATION: http://itmctr.ccebtcm.org.cn/, identifier ITMCTR2025001333.