Multi-omics Study of Clinical Endpoints in CHD (OmiDETCHD)

Guangdong Provincial People's Hospital (Guangdong Provincial Academy of Medical Sciences)

Status: Unknown

Conditions: Coronary Heart Disease

Treatments: Other: validation; Other: Predictive mathematical models; Other: risk factors of adverse cardiovascular events; Other: multi-omics target discovery

Study type: Observational

Funder types: Other

Identifiers

NCT03797339

2017YFC0909301

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 4,000 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• age: 18-80 years
• Chinese Han patients with coronary artery disease
• inpatients undergoing coronary angiography or percutaneous coronary intervention

Exclusion criteria

• 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

Trial design

4,000 participants in 2 patient groups

Discovery cohort

Description:

1000 cases of coronary heart disease follow-up cohort was used for multi-omics target discovery.During the follow-up period, the information about the occurrence and risk factors of adverse cardiovascular events will be collected.

Treatment:

Other: risk factors of adverse cardiovascular events

Other: multi-omics target discovery

Validation corhort

Description:

3000 coronary heart disease follow-up cohorts was used for validating the results from the discovery corhort. During the follow-up period, the occurrence and risk factors of adverse cardiovascular events.Predictive mathematical models based on multi-omics combination will be constructed finally.

Treatment:

Other: risk factors of adverse cardiovascular events

Other: validation

Other: Predictive mathematical models