The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension (TRIMETA-PH)
Primary Purpose
Precapillary Pulmonary Hypertension
Status
Completed
Phase
Phase 2
Locations
Indonesia
Study Type
Interventional
Intervention
Trimetazidine
Placebo oral capsule
Sponsored by
About this trial
This is an interventional treatment trial for Precapillary Pulmonary Hypertension
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
Sites / Locations
- National Cardiovascular Center Harapan Kita Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Sugar pill
trimetazidine
Arm Description
The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.
The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT03273387
First Posted
September 3, 2017
Last Updated
September 11, 2019
Sponsor
Indonesia University
1. Study Identification
Unique Protocol Identification Number
NCT03273387
Brief Title
The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension
Acronym
TRIMETA-PH
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
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
September 10, 2017 (Actual)
Primary Completion Date
November 1, 2018 (Actual)
Study Completion Date
December 14, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indonesia University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Precapillary Pulmonary Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sugar pill
Arm Type
Placebo Comparator
Arm Description
The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.
Arm Title
trimetazidine
Arm Type
Experimental
Arm Description
The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
Intervention Type
Drug
Intervention Name(s)
Trimetazidine
Other Intervention Name(s)
Trizedon MR
Intervention Description
The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Other Intervention Name(s)
sugar pill
Intervention Description
The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.
Primary Outcome Measure Information:
Title
Changes in Right Ventricular Ejection Fraction (RVEF %) After 3 Months Intervention
Description
Right ventricular ejection fraction (RVEF %) assessed by Cardiac MRI at 3 months intervention minus with RVEF at baseline.
Time Frame
Baseline and 3 months after intervention
Secondary Outcome Measure Information:
Title
Changes in Cardiac Fibrosis After 3 Months Intervention
Description
Native T1 mapping (ms) assessed by Cardiac MRI at 3 months intervention minus with Native T1 at baseline.
Time Frame
Baseline and 3 months after intervention
Title
Changes in Functional Capacity After 3 Month Intervention
Description
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.
Time Frame
Baseline and 3 months after intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hary Sakti Muliawan, MD,PhD
Organizational Affiliation
Department Cardiology and Vascular Medicine Universitas Indonesia
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cardiovascular Center Harapan Kita Hospital
City
Jakarta
ZIP/Postal Code
11420
Country
Indonesia
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension
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