Multi-omics Study of the Individual Differences of Drug Efficacy and Toxicity in Patients With Coronary Heart Disease
试验速览
- 阶段
- 不适用
- 入组人数
- 4,000
- 试验地点
- 5
- 主要终点
- Death
研究概览
简要总结
This study aimed to explore underlying mechanisms of individual differences in drugs for coronary heart disease treatment and its association with adverse consequences. It will enroll approximately 4000 coronal heart disease patients aged between 18 and 80 years in mainland China and follow-up for at least 1 years. Questionnaires, anthropometric measures, laboratory tests, and biomaterials will be collected . The principal clinical outcomes of the study consist of ischemia attack , cardiac death, renal injury,and myotoxic activity.
详细描述
The study is a multicenter prospective cohort study, aimed to explore underlying mechanisms of individual differences in drugs for coronary heart disease treatment and its association with adverse consequences.The genomic genotype, DNA methylation and metabolome of 1000 patients with coronary heart disease were determined using illumina high-density genotyping chip, high-throughput sequencing and high-resolution mass spectrometry. Blood exposures of statins and metoprolol and its metabolites was determined by UPLC-MS/MS.
The biological network using cross-omics analysis was reconstructed to identify potential causative key genes, bacteria, and endogenous metabolite targets that cause differences in individual responses. A machine identification algorithm selecting clinical factors and multi-omics targets was used to establish a predictive mathematical model.
A multi-center clinical cohort of 3000 coronal heart disease patients was used to verify the effects of various levels of omic targets on drug blood exposures, efficacy and toxic side effects. A comprehensive model based on multi-target combination of individualized drugs was constructed, and the predictive effect was clinically analyzed.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age: 18-80 years
- •Chinese Han patients with coronary artery disease
- •inpatients undergoing coronary angiography or percutaneous coronary intervention
排除标准
- •renal insufficiency (defined as serum creatinine concentration > 2 times the upper limit of normal [230 μmol/L], renal transplantation or dialysis)
- •hepatic insufficiency (defined as serum transaminase concentration > 2 times the upper limit of normal [80 U/L], or a diagnosis of cirrhosis)
- •pre-existing bleeding disorders
- •being pregnant or lactating
- •advanced cancer or haemodialysis
- •history of thyroid problems, and use of antithyroid drugs or thyroid hormone medication
- •incomplete information about cardiovascular events during follow-up
结局指标
主要结局
Death
时间窗: from date of baseline examination until the date of first documented death,up to 48 months
All-cause death
次要结局
- CI-AKI(more than 6 h within 48 h after Coronary Angiography)
- MACE(from date of baseline examination until the date of first documented cardiovascular events,up to 48 months)
- Bleeding(from date of baseline examination until the date of first documented bleeding,up to 48 months)
- Statin-induced myopathy (SIM)(from date of baseline examination until the date of first documented SIM,up to 48 months)
研究者
ShiLong Zhong
Professor
Guangdong Provincial People's Hospital