The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension (TRIMETA-PH)

The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension Patients in National Cardiovascular Center Harapan Kita Hospital Indonesia

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.

Study Overview

• Status: Completed
• Conditions: Precapillary Pulmonary Hypertension
• Intervention / Treatment: Drug: Placebo oral capsule; Drug: Trimetazidine

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta, Indonesia, 11420
    • National Cardiovascular Center Harapan Kita Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sugar pill; The participant will received placebo oral capsule 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.; Other Names: sugar pill
Experimental: trimetazidine; The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.	Drug: Trimetazidine; The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.; Other Names: Trizedon MR

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Cardiac Fibrosis After 3 Months Intervention	Native T1 mapping (ms) assessed by Cardiac MRI at 3 months intervention minus with Native T1 at baseline.	Baseline and 3 months after intervention
Changes in Functional Capacity After 3 Month 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.	Baseline and 3 months after intervention

Collaborators and Investigators

• Sponsor: Indonesia University
• Investigators: Principal Investigator: Hary Sakti Muliawan, MD,PhD, Department Cardiology and Vascular Medicine Universitas Indonesia

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2017
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): December 14, 2018

Study Registration Dates

• First Submitted: September 3, 2017
• First Submitted That Met QC Criteria: September 3, 2017
• First Posted (Actual): September 6, 2017

Study Record Updates

• Last Update Posted (Actual): October 3, 2019
• Last Update Submitted That Met QC Criteria: September 11, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Vasodilator Agents; Trimetazidine
• Other Study ID Numbers: LB.02.01/VII/172/KEP.009/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No