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Trimetazidine in Pulmonary Artery Hypertension

Primary Purpose

Pulmonary Artery Hypertension

Status
Unknown status
Phase
Phase 2
Locations
Chile
Study Type
Interventional
Intervention
Trimetazidine
Sponsored by
Pontificia Universidad Catolica de Chile
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Artery Hypertension

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital Clinico Pontificia Universidad Catolica de ChileRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Sugar pill

Trimetazidine

Arm Description

Placebo 1 pill bid, 3 months

Trimetazidine 35 mg bid for 3 months

Outcomes

Primary Outcome Measures

Changes in right ventricular (RV) function
Changes in RV function assessed by echo 3d (strain-strain rate)

Secondary Outcome Measures

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

Full Information

First Posted
March 31, 2014
Last Updated
April 2, 2014
Sponsor
Pontificia Universidad Catolica de Chile
Collaborators
Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
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1. Study Identification

Unique Protocol Identification Number
NCT02102672
Brief Title
Trimetazidine in Pulmonary Artery Hypertension
Official Title
Comprehensive Evaluation of Right Ventricular Function, Ventricular Remodeling and Micro RNA Profiling in Pulmonary Artery Hypertension: Effects of a Fatty Acid Oxidation Inhibitor
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Unknown status
Study Start Date
March 2014 (undefined)
Primary Completion Date
December 2016 (Anticipated)
Study Completion Date
December 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pontificia Universidad Catolica de Chile
Collaborators
Fondo Nacional de Desarrollo Científico y Tecnológico, Chile

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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 "

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Artery Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sugar pill
Arm Type
Placebo Comparator
Arm Description
Placebo 1 pill bid, 3 months
Arm Title
Trimetazidine
Arm Type
Experimental
Arm Description
Trimetazidine 35 mg bid for 3 months
Intervention Type
Drug
Intervention Name(s)
Trimetazidine
Other Intervention Name(s)
Vastarel
Primary Outcome Measure Information:
Title
Changes in right ventricular (RV) function
Description
Changes in RV function assessed by echo 3d (strain-strain rate)
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Changes in exercise capacity
Description
Changes in exercise capacity assessed by 6 minute walk test
Time Frame
3 months
Title
Changes in symptoms
Description
Changes in Borg dyspnea index
Time Frame
3 months
Title
Changes in biomarkers
Description
Changes in B-type natriuretic peptide, galectin-3 and rho-kinase activity
Time Frame
3 months
Title
Time to clinical worsening
Description
Time to first PAH related medical event (ER evaluation, hospitalization or death)
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: PAH patients belonging to the following subgroups of the updated Dana Point Classification Group 1 Idiopathic PAH Heritable PAH Drug or toxin-induced PAH PAH associated with connective tissue disease PAH associated to congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pablo F Castro, MD
Phone
+56223543334
Email
pcastro@med.puc.cl
First Name & Middle Initial & Last Name or Official Title & Degree
Hugo E Verdejo, MD, PhD
Phone
+569223543624
Email
hverdejo@med.puc.cl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pablo F Castro, MD
Organizational Affiliation
Pontificia Universidad Catolica de Chile
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Clinico Pontificia Universidad Catolica de Chile
City
Santiago
State/Province
Metropolitana
ZIP/Postal Code
8330024
Country
Chile
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silvana A Llevaneras, RN
Phone
+56223548236
Email
sllevane@med.puc.cl

12. IPD Sharing Statement

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Trimetazidine in Pulmonary Artery Hypertension

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