Clinical trial NCT03887013: Cardiac Metabolic Modulator Treatment for Improvement of Diastolic Function in Patients With Coronary Heart Disease
Official title: Cardiac Metabolic Modulator Treatment for Improvement of Left Ventricular Diastolic Function in Patients With Coronary Heart Disease: a Prospective, Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Coronary Heart Disease
Diastolic Dysfunction
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
First posted: 2019-03-22
Enrollment: 226
Sex: ALL
Minimum age (years): 50
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage difference of patients with II or III degree diastolic dysfunction in each arm
timeFrame: Within 6 months after patients being enrolled
Secondary outcomes:
measure: Average E/e' ratio change between week 24 and baseline
timeFrame: Within 6 months after patients being enrolled
measure: E' velocity change of septum or of left ventricular lateral wall in m/s between week24 and baseline
timeFrame: Within 6 months after patients being enrolled
measure: Velocity of tricuspid regurgitation change in m/s between week 24 and baseline
timeFrame: Within 6 months after patients being enrolled
measure: Index of left atrium volume change between week 24 and baseline
timeFrame: Within 6 months after patients being enrolled
measure: Concentration of the plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) change in pg/ml between week 24 and baseline
timeFrame: Within 6 months after patients being enrolled
measure: Number of participants with cardiovascular death and being rehospitalized for heart failure within 24 weeks treatment
timeFrame: Within 6 months after patients being enrolled
measure: Concentration of glycated hemoglobin (HbA1c) change in patients with diabetes mellitus (DM) between week 24 and baseline
timeFrame: Within 6 months after patients being enrolled
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases
state: Beijing
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Yan Zhao
role: PRINCIPAL_INVESTIGATOR
References: