Cardiac Metabolic Modulator Treatment for Improvement of Diastolic Function in Patients With Coronary Heart Disease

Phase 4

• Conditions: Coronary Heart Disease; Diastolic Dysfunction
• Interventions: Drug: Trimetazidine

• Registration Number: NCT03887013
• Lead Sponsor: China National Center for Cardiovascular Diseases

Brief Summary

Based on accumulating evidence showing that impaired cardiac energetic metabolism plays important role in the mechanism of cardiac diastolic dysfunction,the study is designed to evaluate whether metabolic modulator treatment with trimetazidine could have beneficial effects on patients with coronary heart disease(CHD) and ventricular diastolic dysfunction.This study is a prospective,randomised,open-label trial to assess the efficacy of trimetazidine treatment in improving diastolic function in CHD patients with diastolic dysfunction.

Detailed Description

The primary objective of this trial is to determine whether the 24-week trimetazidine therapy, as an adjunct to routine treatment for CHD, would improve diastolic function in patients with ischemic heart disease compared to the routine treatment.

Study Timeline

• Status Verified: 2018-10
• Study First Submitted: 2019-03-19
• Study First Submitted QC: 2019-03-21
• Last Update Submitted: 2019-03-21
• Study First Posted: 2019-03-22
• Study Start: 2019-03-25
• Last Update Posted: 2019-03-25
• Primary Completion: 2020-10
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 226

Inclusion Criteria

• Aged between 50 and 79 years,male or female (without pregnancy).
• Diagnosed CHD by coronary angiography,with stenoses in main bifurcations less than 70% after PCI treatment.
• Left ventricular ejection fraction(LVEF) more than 50% assessed by ultracardiography.
• Characteristics of diastolic dysfunction by ultracardiography (more than 2 criteria as following):(1)Average E/e'>14,(2)Septal e' velocity <7 cm/s or lateral e' velocity <10 cm/s,(3)Tricuspid regurgitation (TR) velocity >2.8m/s,(4)Left atrium (LA) volume index >34ml/m2.
• Not yet being treated by trimetazidine.
• Provided informed consent.

Exclusion Criteria

• Acute heart failure or acute exacerbation of chronic heart failure.
• LVEF less than 50% at admission or in the past.
• History of malignant tumor or life expectancy under 12 months.
• Acute myocardial infarction or unstable angina pectoris within 3 months.
• Scheduled coronary artery bypass grafting therapy within 6 months.
• Diagnosed or considered valvular heart disease, hypertrophic cardiomyopathy,restrictive cardiomyopathy or pericardium diseases.
• Significant hepatic impairment (Serum glutamate-pyruvate transaminase more than 3 times normal upper limit) or severe renal dysfunction (eGFR≤30 ml/min/1.73m2).
• Known or considered Parkinson's Disease.
• Known hypersensitivity or intolerance to trimetazidine.
• Pregnancy and lactation period.
• Any disorder which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol.
• Participation in another clinical trial within the past 30 days.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CHD routine therapy+Trimetazidine	Trimetazidine	Apart from the drug and PCI therapy mentioned above,patients will be given treatment of trimetazidine.

Primary Outcome Measures

Name	Time	Method
Percentage difference of patients with II or III degree diastolic dysfunction in each arm	Within 6 months after patients being enrolled	II or III degree diastolic dysfunction is defined as average E/e' ratio more than 10

Secondary Outcome Measures

Name	Time	Method
Average E/e' ratio change between week 24 and baseline	Within 6 months after patients being enrolled	Average e/e' is evaluated by ultracardiography
Number of participants with cardiovascular death and being rehospitalized for heart failure within 24 weeks treatment	Within 6 months after patients being enrolled	This number will be acquired during follow up
Concentration of glycated hemoglobin (HbA1c) change in patients with diabetes mellitus (DM) between week 24 and baseline	Within 6 months after patients being enrolled	HbA1c (%)is tested by Fuwai Hospital laboratory
E' velocity change of septum or of left ventricular lateral wall in m/s between week24 and baseline	Within 6 months after patients being enrolled	E' velocity change of septum or of left ventricular lateral wall is evaluated by ultracardiography
Velocity of tricuspid regurgitation change in m/s between week 24 and baseline	Within 6 months after patients being enrolled	Velocity of tricuspid regurgitation is evaluated by ultracardiography
Index of left atrium volume change between week 24 and baseline	Within 6 months after patients being enrolled	Index of left atrium volume is evaluated by ultracardiography
Concentration of the plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) change in pg/ml between week 24 and baseline	Within 6 months after patients being enrolled	NT-proBNP is tested by Fuwai Hospital laboratory

Trial Locations

Locations (1)

Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases; 🇨🇳 Beijing, Beijing, China