The ImPact of Trimetazidine on MicrOcirculation After Stenting for Stable Coronary Artery Disease (PATMOS)

June 1, 2023 updated by: Ivan Ilic, MD PhD, Clinical Hospital Center Zemun

The Study to Assess the Effect of Trimetazidine on Index of Microcirculatory Resistance (IMR), Measured by Coronary Pressure and Temperature Wire, in Patients With Stable Coronary Artery Disease

The study should enrol 50 patients with stable coronary artery disease scheduled for elective percutaneous coronary intervention of single, de novo lesion of native coronary artery. Patients will be randomized to orally given trimetazidine on top of standard medical therapy for stable coronary artery disease versus standard therapy only. The randomization will begin 48 hrs before intervention. Index of microcirculatory resistance (IMR) will be measured by thermodilution method using coronary pressure and temperature wire before and after stent implantation. Echocardiography will be performed before intervention and within 30 minutes after intervention. Patients will be followed clinically for a period of one year.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study is prospective, single blinded randomized study that will be performed in a single tertiary cardiovascular centre. The inclusion criteria for the study are the presence of the stable angina or positive stress test, Canadian Cardiovascular Society (CCS) class less than IV and an indication for percutaneous intervention of a single, de novo, native coronary artery lesion with diameter stenosis greater than 70%. Exclusion criteria are left ventricular systolic function (LVEF) less than 30%, acute coronary syndrome, a history of previous myocardial infarction in the territory supplied by the treated coronary artery, existence of the collateral circulation to another coronary artery supplied by the treated vessel, chronic total occlusion, significant bifurcation lesion, previous surgical revascularization, significant renal function impairment (GFR less than 60ml/min), allergy to any constituents of trimetazidine, aspirin and antiplatelet medications used after PCI, contrast agents, contraindication to adenosine use. The patient with disorders like Parkinson disease, parkinsonian symptoms, tremors, restless leg syndrome, and other related movement disorders will also be excluded from the study.

Patients, who are trimetazidine naïve, will be randomly assigned to receive either trimetazidine plus previous medications (TMZ group) 48h before scheduled PCI or just previous medication (Control group). Paients that are TMZ naïve and randomized to TMZ group will be given loading of 70mg of TMZ on day 0. The PCI operator would not be aware if the patient receives TMZ. All patients will be pretreated before PCI with aspirin 100mg/day, Clopidogrel 75mg/day seven days before the procedure. Patient will be asked to sign informed consent form before entering the study and the study protocol was approved by Ethics committee of Clinical Hospital Center Zemun.

Patients will undergo PCI intervention on day 2. Before PCI patients will receive heparin 80 - 100 IU/kg iv. PCI procedure has to be performed with angioplasty balloon predilation of the treated lesion to avoid influence of direct stenting on IMR measurement. The stenting will be performed according to operator's preference. The fractional flow reserve (FFR), coronary flow reserve (CFR) and IMR will be measured before and after PCI using coronary pressure - / thermistor - tipped wire (Radi Pressure Wire Certus, St Jude Medical, Uppsala, Sweden). Maximal hyperemia will be achieved using iv infusion of adenosine (140mcg/kg/min) during the procedure. The pressure wire will be advanced through 6F guiding catheter to position the pressure sensor at a point 10 mm distal to the distal end of the stenosis or the stent after PCI procedure. Three injections of 3ml normal saline at room temperature will be administered via guiding catheter at baseline before starting PCI procedure and at maximal hyperemia. The transit time will be measured as the time that elapses between the moment when one-half of the saline had been injected (defined as T0, and determined on the temperature curve from the shaft of the wire) and the moment when one-half of the saline had passed the sensor. Simultaneous recordings of mean aortic pressure (guiding catheter, Pa) and mean distal coronary pressure (distal pressure sensor, Pd) will also be obtained at baseline and during maximal hyperemia. FFR will be calculated by dividing the mean distal coronary pressure (Pd) by the mean aortic pressure (Pa) during maximal hyperemia. CFR will be calculated as a ratio of mean transit time at basal condition (Tbas) and after inducing hyperemia (Thyp). The IMR will be calculated using the following equation: IMR = Pa x Thyp [(Pd - Pw) / (Pa - Pw)], where Pw is the coronary wedge pressure. Pw will be measured as the distal coronary pressure Pd (from the distal pressure and temperature sensor) during complete balloon occlusion of the vessel with the angioplasty balloon during PCI.

Coronary angiograms will be analyzed offline using a computer-assisted, automated edge-detection algorithm using dedicated software Axiom Sensis (Siemens, Erlangen, Germany) by an independent operator not involved in the study or PCI procedure. QCA of the lesion, TIMI coronary flow, TIMI myocardial blush and TIMI frame count before and after PCI will be assessed.

Comprehensive echocardiogram with 2D-strain analysis will be done before and immediately after PCI procedure within 30 minutes after its end.

After the procedure, the patients who had an uneventful PCI will stay in the hospital for 24 h. Blood samples for Troponin I, creatin kinaze (CK) and CK-MB will be collected at 6, 12 and 24 h after the procedure, and for C reactive protein (CRP) after 24h. Complications of the interventions will be documented in the patients study file. Periprocedural myocardial necrosis is defined as rise in troponin I level three times 99th percentile upper limit of reference range, according to definition of myocardial infarction for clinical trials on coronary interventions.

After discharge from the hospital patients will be followed according to hospital protocol. Patients will be seen in an office visit 30 days and 6 months after baseline PCI procedure. At 12 months after baseline procedure patients' vital status will be assessed by telephone interview.

Statistical analysis

Continuous data will be summarized as the means ± SD. Categorical data will be summarized as counts and percentages. Unpaired t-tests will be used for comparing the continuous variables, if the distribution is normal, and Mann Whitney U test if the distribution is not normal. Chi-squared test and Fisher's exact test will be used for categorical vari¬ables. Multivariate logistic regression analysis will be performed to determine independent predictors of impaired IMR after PCI. Univariate analysis would be conducted first to identify potential factors for impaired IMR. The likelihood-ratio test will be used, and the variables with a p value < 0.2 would be included in the multivariate model. A p value of p<0.05 will be considered to be statistically significant. All statistical analyses will be performed with the PASWStatistics 18.0 statistical software (SPSS Inc, Chicago, Illinois, USA).

Based on the previous studies it was estimated that study sample size needed for expected difference in IMR values of 9 to be obtained between study groups (power 80%) is around 40 patients.

Study Type

Interventional

Enrollment (Actual)

71

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Serbia
      • Belgrade, Serbia, 11040
        • Institute for Cardiovascular Diseases Dedinje

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • presence of the stable angina or positive stress test
  • Canadian Cardiovascular Society (CCS) class less than IV
  • single, de novo, native coronary artery lesion
  • diameter stenosis greater than 70%.

Exclusion Criteria:

  • left ventricular systolic function (LVEF) less than 30%
  • acute coronary syndrome
  • history of previous myocardial infarction in the territory supplied by the treated coronary artery
  • existence of the collateral circulation to another coronary artery supplied by the treated vessel
  • chronic total occlusion
  • significant bifurcation lesion
  • previous surgical revascularization
  • significant renal function impairment (GFR less than 60ml/min) allergy to any constituents of trimetazidin, aspirin and antiplatelet medications used after PCI, contrast agents
  • contraindication to adenosine use
  • Parkinson disease
  • parkinsonian symptoms, tremors, restless leg syndrome, and other related movement disorders

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: trimetazidin
Patients, who are trimetazidine (TMZ) naïve, will be randomly assigned to receive trimetazidine plus previous medications (TMZ group) 48h before scheduled PCI- Paients that are TMZ naïve and randomized to TMZ group will be given oral loading of 70mg TMZ.
Drug: trimetazidine
After being randomized to Trimetazidin and cardiac medication vs. only cardiac medication, patient will undergo scheduled PCI of single, new, native coronary artery lesion using balloon predilatation and subsequent stenting.
Other Names:
  • Vastarel MR
  • Preductal MR
  • Trimetacor
No Intervention: Control
Patients, who are TMZ naïve, will be randomly assigned to receive just previous cardiac medication (Control group).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
index of microcirculatory resistance
Time Frame: On day 2 during percutaneous coronary intervention
Trimetazidine given on day 0 before elective percutaneous coronary intervention would decrease microvascular dysfunction by reducing index of microcirculatory resistance (IMR) measured by thermodilution method using coronary pressure and temperature wire on day 2 during PCI
On day 2 during percutaneous coronary intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
periprocedural myocardial necrosis
Time Frame: on day 2 after PCI
Periprocedural myocardial necrosis will be measured by collecting blood samples for Troponin I, CK and CK-MB at 6, 12 and 24 h after the procedure.
on day 2 after PCI

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
change in 2D myocardial strain
Time Frame: on day 2 30 minutes after completion of PCI procedure
Comprehensive echocardiogram with 2D-strain analysis will be done before and immediately after PCI procedure to correlate change in IMR with possible change in 2D strain after PCI
on day 2 30 minutes after completion of PCI procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clinical Hospital Center Zemun

Investigators

  • Study Director: Petar Otasevic, MD, PhD, Institute for cardiovascular diseases Dedinje Belgrade, Serbia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (Actual)

March 1, 2023

Study Completion (Actual)

March 1, 2023

Study Registration Dates

First Submitted

March 29, 2014

First Submitted That Met QC Criteria

April 4, 2014

First Posted (Estimated)

April 8, 2014

Study Record Updates

Last Update Posted (Actual)

June 2, 2023

Last Update Submitted That Met QC Criteria

June 1, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZEM - CARD - 002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Coronary Artery Disease

Clinical Trials on trimetazidine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cambodia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe