Clinical trial NCT03273387: The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension
Official title: The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension Patients in National Cardiovascular Center Harapan Kita Hospital Indonesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Precapillary Pulmonary Hypertension
Lead sponsor: Indonesia University
Sponsor class: OTHER
First posted: 2017-09-06
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will evaluate the effect of trimetazidine versus placebo in addition to standard pulmonary arterial hypertension regime on right ventricular function in pulmonary arterial hypertension patients.

Detailed description: Right ventricular dysfunction is the worst mortality predictor in pulmonary arterial hypertension (PAH). Recent study has described that approximately 25% of PAH patients will developed into right ventricular failure despite therapeutic reduction of pulmonary vascular resistance. Subsequently, several studies have shown that fatty acid accumulation in right ventricle was inversely correlated with right ventricular function in PAH patients. Several PAH animal studies have revealed that metabolic glucose oxidation impairment through increased aerobic glycolysis, mitochondrial dysfunction, and lipotoxicity play significant role in right ventricular failure. Moreover, several pulmonary hypertension animal studies have demonstrated the benefit of partial fatty acid inhibitor such as trimetazidine on right ventricle function. It was hypothesize that trimetazidine improved right ventricular function through indirect effect of increased glucose oxidation by blocking the Randle cycle. Therefore, we hypothesize that trimetazidine can improve right ventricular function in pulmonary arterial hypertension patients.

Eligibility criteria: Inclusion Criteria:

* Pre-capillary Pulmonary Hypertension patients assessed by right heart catheterization
* Signed informed consent

Exclusion Criteria:

* Patient belonging to post-capillary, Isolated post-capillary, or combined post -capillary and pre-capillary pulmonary hypertension according to 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.
* Moderate to severe chronic pulmonary obstructive disease
* Right Ventricular Ejection Fraction \> 45% assessed by cardiac magnetic resonance.
* Documented left ventricular dysfunction with left ventricular ejection fraction \< 50% assessed by cardiac magnetic resonance.
* Severe renal impairment (Serum creatinine \> 2.5 mg/dL, eGFR \< 30ml/min/1.73 m\^2, or routine dialysis treatment).
* Malignant arrhythmia such as total atrioventricular block or ventricular fibrillation or unstable ventricular tachycardia.
* Patients who are receiving or have been receiving any investigational drugs within 1 month before the baseline visit
* Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements
* Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
* Females who are lactating or pregnant or those who plan to become pregnant during the study
* Known Parkinson disease
* Known hypersensitivity to any of the drug formulation

Primary outcomes:
measure: Changes in Right Ventricular Ejection Fraction (RVEF %) After 3 Months Intervention
timeFrame: Baseline and 3 months after intervention
Secondary outcomes:
measure: Changes in Cardiac Fibrosis After 3 Months Intervention
timeFrame: Baseline and 3 months after intervention
measure: Changes in Functional Capacity After 3 Month Intervention
timeFrame: Baseline and 3 months after intervention
Other outcomes:
Locations:
city: Jakarta
country: Indonesia
facility: National Cardiovascular Center Harapan Kita Hospital
Study officials:
affiliation: Department Cardiology and Vascular Medicine Universitas Indonesia
name: Hary Sakti Muliawan, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: