Multi-omics Study of Clinical Endpoints in CHD

Coronary Heart Disease Clinical Trial

— OmiDETCHD  

Official title:

Multi-omics Study of the Individual Differences of Drug Efficacy and Toxicity in Patients With Coronary Heart Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03797339
• Other study ID #: 2017YFC0909301
• Status: Recruiting
• Start date: July 1, 2017
• Est. completion date: December 31, 2020

Study information

• Verified date: February 2019
• Source: Guangdong General Hospital
• Contact: Shilong Zhong, Ph.D
• Phone: 862083827812
• Email: zhongsl[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4000
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

Other:
• risk factors of adverse cardiovascular events
During the follow-up period,general information(age, sex, BMI, blood pressure, the history of drink and smoke, medical history, etc).Blood biochemistry parameters(Lipid, hsCRP levels, etc)and other laboratory examination parameters will be collected
• multi-omics target discovery
Genome-wide genotype , DNA methylation and metabolomes were determined using illumina high-density genotyping chips, high-throughput sequencing, and high-resolution mass spectrometry respectly. Blood exposure of statins and metoprolol and its metabolites was determined by UPLC-MS/MS.
• validation
The genome-wide genotype of patients with coronary heart disease was detected using the illumina chip. The methylation level of the functional region was detected by the target region enrichment methylation sequencing method. Intestinal flora differences were detected using 16SrDNA high-throughput sequencing.
• Predictive mathematical models
Machine learning algorithms such as multiple linear regression or Bayesian classification are used to optimize clinical factors and multi-group targets to establish predictive mathematical models.

Locations

Country	Name	City	State
China	XiangYa Hospital Central South University	Changsha	Hunan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Guangdong General Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	Renji Hospital Affiliated to Shanghai Jiaotong University	Shanghai	Shanghai

Sponsors (5)

Lead Sponsor	Collaborator
Guangdong General Hospital	First Affiliated Hospital, Sun Yat-Sen University, RenJi Hospital, West China Hospital, Xiangya Hospital of Central South University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SYNTAX score	It is mainly used for the treatment of left main coronary artery lesions and/or three-vessel lesions.Patients with a score of =33 are recommended for CABG. Patients with a score between 23 and 32 can choose either PCI or CABG. Patients with a score of =22 are recommended for PCI and CABG.	more than 6 h within 48 h after Coronary Angiography
Primary	Death	All-cause death	from date of baseline examination until the date of first documented death,up to 48 months
Secondary	MACE	MACE was defined as the occurrence of cardiac death, nonfatal myocardial infarctions, coronary revascularisation and cerebral infraction.	from date of baseline examination until the date of first documented cardiovascular events,up to 48 months
Secondary	Bleeding	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.	from date of baseline examination until the date of first documented bleeding,up to 48 months
Secondary	Statin-induced myopathy (SIM)	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.	from date of baseline examination until the date of first documented SIM,up to 48 months
Secondary	CI-AKI	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	more than 6 h within 48 h after Coronary Angiography