Trimetazidine in Pulmonary Artery Hypertension

Comprehensive Evaluation of Right Ventricular Function, Ventricular Remodeling and Micro RNA Profiling in Pulmonary Artery Hypertension: Effects of a Fatty Acid Oxidation Inhibitor

Pulmonary artery hypertension (PAH) is a chronic and progressive disease that affects 15 persons per million. Although current therapy has improve disease prognosis, PAH still has a poor survival, with a median survival of 2.8 years after diagnosis. In the last few years new key elements in PAH pathogenesis have been discovered, such as the role of metabolism in disease onset and progression. In fact, PAH pulmonary smooth muscle cells switch into a glycolytic phenotype which resembles the metabolism of cancer cells. The investigators hypothesis is that "fatty acid oxidation inhibition reverts the PAH adverse phenotype by restoring mitochondrial function and morphology, decreasing proliferation and restoring apoptosis susceptibility in pulmonary smooth muscle cells "

Study Overview

• Status: Unknown
• Conditions: Pulmonary Artery Hypertension
• Intervention / Treatment: Drug: Trimetazidine

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Chile
  • Metropolitana
    • Santiago, Metropolitana, Chile, 8330024
      • Recruiting
      • Hospital Clínico Pontificia Universidad Católica de Chile
      • Contact: Silvana A Llevaneras, RN; Phone Number: +56223548236; Email: sllevane@med.puc.cl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• PAH patients belonging to the following subgroups of the updated Dana Point Classification Group 1

  1. Idiopathic PAH
  2. Heritable PAH
  3. Drug or toxin-induced PAH
  4. PAH associated with connective tissue disease
  5. PAH associated to congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair
  6. PAH associated to HIV infection
• Documented hemodynamic diagnosis of PAH by right ventricular catheterization performed any time prior to screening
• Signed informed consent

Exclusion Criteria:

• Patients belonging to the subgroups of the updated Dana Point Classification Group I not listed in the inclusion criteria
• Patients belonging to the groups 2-5 of the updated Dana Point Classification Group
• Moderate to severe chronic pulmonary obstructive disease
• Documented left ventricular dysfunction
• Severe renal impairment (Serum creatinine > 2.5 mg/dL)
• 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
• Life expectancy less than 12 months
• Females who are lactating or pregnant or those who plan to become pregnant during the study
• Known hypersensitivity to any of the excipients of the drug formulation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Sugar pill; Placebo 1 pill bid, 3 months
EXPERIMENTAL: Trimetazidine; Trimetazidine 35 mg bid for 3 months	Drug: Trimetazidine; Other Names: Vastarel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in right ventricular (RV) function	Changes in RV function assessed by echo 3d (strain-strain rate)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in exercise capacity	Changes in exercise capacity assessed by 6 minute walk test	3 months
Changes in symptoms	Changes in Borg dyspnea index	3 months
Changes in biomarkers	Changes in B-type natriuretic peptide, galectin-3 and rho-kinase activity	3 months
Time to clinical worsening	Time to first PAH related medical event (ER evaluation, hospitalization or death)	3 months

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Collaborators: Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
• Investigators: Principal Investigator: Pablo F Castro, MD, Pontificia Universidad Catolica de Chile

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ANTICIPATED): December 1, 2016
• Study Completion (ANTICIPATED): December 1, 2017

Study Registration Dates

• First Submitted: March 31, 2014
• First Submitted That Met QC Criteria: April 2, 2014
• First Posted (ESTIMATE): April 3, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): April 3, 2014
• Last Update Submitted That Met QC Criteria: April 2, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Vasodilator Agents; Trimetazidine
• Other Study ID Numbers: 13-229