Multi-omics Study of Clinical Endpoints in CHD

• Conditions: Coronary Heart Disease
• Interventions: Other: risk factors of adverse cardiovascular events; Other: validation; Other: multi-omics target discovery; Other: Predictive mathematical models

• Registration Number: NCT03797339
• Lead Sponsor: Guangdong Provincial People's Hospital

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.

Study Timeline

• Study Start: 2017-07-01
• Study First Submitted: 2019-01-05
• Study First Submitted QC: 2019-01-05
• Study First Posted: 2019-01-09
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-11
• Last Update Posted: 2019-02-12
• Primary Completion: 2019-12-31
• Study Completion: 2020-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 4000

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Discovery cohort	risk factors of adverse cardiovascular events	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.
Validation corhort	validation	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.
Discovery cohort	multi-omics target discovery	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.
Validation corhort	Predictive mathematical models	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.
Validation corhort	risk factors of adverse cardiovascular events	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.

Primary Outcome Measures

Name	Time	Method
Death	from date of baseline examination until the date of first documented death,up to 48 months	All-cause death

Secondary Outcome Measures

Name	Time	Method
CI-AKI	more than 6 h within 48 h after Coronary Angiography	CI-AKI was diagnosed if a patient had an absolute increase in serum creatinine (sCr) concentration ≥ 0.3 mg/dl (26.4 μmol/L) from baseline or a relative increase ≥ 50 % in sCr concentration for more than 6 h within 48 h after surgery
MACE	from date of baseline examination until the date of first documented cardiovascular events,up to 48 months	MACE was defined as the occurrence of cardiac death, nonfatal myocardial infarctions, coronary revascularisation and cerebral infraction.
Bleeding	from date of baseline examination until the date of first documented bleeding,up to 48 months	Bleeding was the six-month incidence of combined alarming, internal, and nuisance bleeding events defined according to Serebruany et al15. Alarming bleeding included bleeding requiring a transfusion, intracranial bleeding, and life-threatening bleeding. Internal bleeding included haematoma, epistaxis, blood loss from the mouth, vagina, melaena, eye bleed, haematuria, and haematemesis. Nuisance bleeding included easy bruising, bleeding from small cuts, petechiae, and ecchymosis.
Statin-induced myopathy (SIM)	from date of baseline examination until the date of first documented SIM,up to 48 months	The definition of SIM from statin treatment was based on the patients' subjective sense of muscular pain as well as CK elevations. These muscular side effects included myalgia (muscle pain/ache without serum CK elevations), other muscle-related symptoms such as weakness, cramps, spasms, soreness and twitching, CK elevations without physical symptoms, myositis or other muscle symptoms with CK elevations, and rhabdomyolysis.

Trial Locations

Locations (5)

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China

The First Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China

Guangdong General Hospital; 🇨🇳 Guangzhou, Guangdong, China

Renji Hospital Affiliated to Shanghai Jiaotong University; 🇨🇳 Shanghai, Shanghai, China

XiangYa Hospital Central South University; 🇨🇳 Changsha, Hunan, China