The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension

Overview

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.

Full Title of Study: “The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension Patients in National Cardiovascular Center Harapan Kita Hospital Indonesia”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: November 1, 2018

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.

Interventions

  • Drug: Trimetazidine
    • The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
  • Drug: Placebo oral capsule
    • The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.

Arms, Groups and Cohorts

  • Placebo Comparator: Sugar pill
    • The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.
  • Experimental: trimetazidine
    • The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.

Clinical Trial Outcome Measures

Primary Measures

  • Changes in Right Ventricular Ejection Fraction (RVEF %) After 3 Months Intervention
    • Time Frame: Baseline and 3 months after intervention
    • Right ventricular ejection fraction (RVEF %) assessed by Cardiac MRI at 3 months intervention minus with RVEF at baseline.

Secondary Measures

  • Changes in Cardiac Fibrosis After 3 Months Intervention
    • Time Frame: Baseline and 3 months after intervention
    • Native T1 mapping (ms) assessed by Cardiac MRI at 3 months intervention minus with Native T1 at baseline.
  • Changes in Functional Capacity After 3 Month Intervention
    • Time Frame: Baseline and 3 months after intervention
    • Functional capacity assessed by SF-36 score after 3 month intervention minus with functional capacity at baseline. SF-36 functional capacity score scale 0 to 100 with better functional capacity along with higher score.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Indonesia University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Hary Sakti Muliawan, MD, PhD, MD,PhD – Indonesia University
  • Overall Official(s)
    • Hary Sakti Muliawan, MD,PhD, Principal Investigator, Department Cardiology and Vascular Medicine Universitas Indonesia

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