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

Cardiac Metabolic Modulator Treatment for Improvement of Left Ventricular Diastolic Function in Patients With Coronary Heart Disease: a Prospective, Randomized Controlled Study

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.

Study Overview

• Status: Unknown
• Conditions: Coronary Heart Disease; Diastolic Dysfunction
• Intervention / Treatment: Drug: Trimetazidine

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 Type: Interventional
• Enrollment (Anticipated): 226
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100037
      • Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: CHD routine therapy; Patients with CHD will be treated with evidence-based therapy including antiplatelet drugs,beta-blockers,statins,angiotensin-converting enzyme inhibitor (ACEI),nitrates,etc. Percutaneous coronary intervention (PCI) could be performed if needed.
EXPERIMENTAL: CHD routine therapy+Trimetazidine; Apart from the drug and PCI therapy mentioned above,patients will be given treatment of trimetazidine.	Drug: Trimetazidine; Trimetazidine is given as 20mg every time and three times per day (Tid) or 20mg every time and two times per day (when renal function is declined).; Other Names: Cardiac metabolic modulator

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases
• Investigators: Principal Investigator: Yan Zhao, Chinese Academy of Medical Sciences, Fuwai Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 25, 2019
• Primary Completion (ANTICIPATED): October 1, 2020
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: March 19, 2019
• First Submitted That Met QC Criteria: March 21, 2019
• First Posted (ACTUAL): March 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 25, 2019
• Last Update Submitted That Met QC Criteria: March 21, 2019
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Vasodilator Agents; Trimetazidine
• Other Study ID Numbers: CRFH20180050

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No