Clinical trial NCT03797339: Multi-omics Study of Clinical Endpoints in CHD
Official title: Multi-omics Study of the Individual Differences of Drug Efficacy and Toxicity in Patients With Coronary Heart Disease
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Coronary Heart Disease
Keywords: epigenome
metabolome
microbiome
genome
multi-omics targets
individual drug use
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
Collaborators: name: RenJi Hospital
name: West China Hospital
name: Xiangya Hospital of Central South University
name: First Affiliated Hospital, Sun Yat-Sen University
First posted: 2019-01-09
Enrollment: 4000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Chinese Han patients with coronary artery disease who have ingested metoprolol and statins were prospectively recruited from Guangdong General Hospital, Shanghai Jiao Tong University, Central South University, Sun Yat-sen University and Sichuan University.

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Death
timeFrame: from date of baseline examination until the date of first documented death,up to 48 months
Secondary outcomes:
measure: MACE
timeFrame: from date of baseline examination until the date of first documented cardiovascular events,up to 48 months
measure: Bleeding
timeFrame: from date of baseline examination until the date of first documented bleeding,up to 48 months
measure: Statin-induced myopathy (SIM)
timeFrame: from date of baseline examination until the date of first documented SIM,up to 48 months
measure: CI-AKI
timeFrame: more than 6 h within 48 h after Coronary Angiography
Other outcomes:
measure: SYNTAX score
timeFrame: more than 6 h within 48 h after Coronary Angiography
Locations:
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Changsha
country: China
facility: XiangYa Hospital Central South University
state: Hunan
city: Shanghai
country: China
facility: Renji Hospital Affiliated to Shanghai Jiaotong University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Shilong Zhong, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: