Efficacy and safety of xuezhikang once per day versus two times per day in patients with mild to moderate hypercholesterolaemia (APEX study): a protocol for a multicentre, prospective randomised controlled, open-label, non-inferiority study

Introduction: Reduction in low-density lipoprotein cholesterol (LDL-C) improves clinical outcomes in patients with coronary artery disease. However, rates of lipid-lowering medication adherence are far from ideal. Reducing dosage frequency from multiple dosing to once-daily dosing may improve patients' medication adherence. Xuezhikang (XZK), an extract of Chinese red yeast rice, contains a family of naturally occurring statins and is traditionally prescribed as 600 mg two times per day. A comParative Efficacy study of XZK (APEX study) is designed to test the hypothesis that XZK prescribed 1200 mg once per day (OD group) is non-inferior to 600 mg two times per day (TD group) in patients with hypercholesterolaemia.

Methods and analysis: The APEX study is a multicentre, prospective randomised controlled, open-label, non-inferiority study. We plan to recruit 316 patients aged ≥18 years with a diagnosis of mild to moderate hypercholesterolaemia for primary prevention. Patients will be randomised (1:1) to OD group and TD group. The OD group take XZK 1200 mg once per day after dinner while TD group take a traditional dose of 600 mg, two times per day after meals. Participants will have an 8-week medication period and be followed up at weeks 0, 4 and 8. The primary end point is the mean percentage change from baseline to week 8 in serum LDL-C. Secondary end points are safety and lipid-lowering effect on other lipoproteins and compliance. Data analyses will be on the intention-to-treat principle using non-inferiority analysis.

Ethics and dissemination: The research had been approved by the Clinical Research and Laboratory Animal Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University ((2017)286). The results will be reported through peer-reviewed journals, seminars and conference presentations.

Trial registration number: ChiCTR-IIR-17013660.