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Effect of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients With Acute Myocardial Infarction

Primary Purpose

Coronary Microvascular Disease, Ticagrelor, Thrombolysis

Status
Completed
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
Microbubble Contrasted Echocardiography
Platelet Aggregability
Laboratory
Sponsored by
University of Sao Paulo General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Coronary Microvascular Disease

Eligibility Criteria

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

Inclusion Criteria:

  • age from 18 years old to 75 years old.
  • Patients with a ST-segment elevation AMI with up to 24 hours duration, documented by ischemic symptoms due to atherosclerosis> 10 minutes at rest, treated with pharmacological thrombolysis, acetylsalicylic acid (ASA) and Clopidogrel or Ticagrelor.
  • Cardiac catheterization performed within 4 (± 2) days of the onset of symptoms, which at the end of coronary angiography showed residual obstruction in the "culprit" artery <50% with TIMI 3 flow regardless of whether or not the percutaneous coronary intervention was performed.

Exclusion Criteria:

  • Previous infarction known from the same wall as the current one
  • Any contraindication to the use of Clopidogrel or Ticagrelor
  • Need for oral anticoagulation therapy or aspirin doses greater than 100mg per day.
  • Concomitant oral or intravenous therapy with strong inhibitors of Cytochrome P450, family 3, subfamily A (CYP3A), Substrates of CYP3A with narrow therapeutic indices or strong inducers of CYP3A
  • High risk of bradyarrhythmias
  • Dialysis therapy
  • Clinically important thrombocytopenia known
  • Clinically Significant Anemia
  • Pregnancy or lactation
  • Contraindications to fibrinolytic therapy

Sites / Locations

  • Heart Institute (InCor) - University of Sao Paulo Medical School

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Ticagrelor

Clopidogrel

Arm Description

Patients will be randomized to have Ticagrelor 90mg BID

Patientes will be randomized to have Clopidogrel 75mg once a day

Outcomes

Primary Outcome Measures

Myocardial Perfusion Score Index (MPSI)
Obtained using Microbubble Contrasted Echocardiography

Secondary Outcome Measures

Left ventricular remodeling 90 days after de AMI, using Echocargiography parameters (End diastolic volume, end systolic volume and ejection Fraction)
To compare the parameters of left ventricular remodeling (End diastolic volume, End Systolic Volume, Ejection Fraction) at after 90 days after discharge from the ticagrelor and clopidogrel groups
number of myocardial segments with perfusion deficit in coronary microcirculation
To evaluate the number of myocardial segments with perfusion deficit in coronary microcirculation in the ticagrelor and clopidogrel groups
MPSI in patients submitted to angioplasty
To evaluate MPSI in the subgroups of patients submitted to angioplasty and not submitted to angioplasty
Patients who used clopidogrel prior to randomization and were randomized to ticagrelor
To evaluate MPSI in subgroups of patients who used clopidogrel prior to randomization and were randomized to ticagrelor
Elective versus Urgent Percutaneous Coronary Intervention (PCI)
To compare the ticagrelor and clopidogrel groups in patients who had elective or urgent PCI
Platelet aggregability
To evaluate the platelet aggregability in the ticagrelor and clopidogrel groups obtained immediately before Myocardial Contrasted Echocardiography (MCE) by Multiplate
Time Ticagrelor or Clopidogrel is administered
Evaluate the main objective of the study in two subgroups: 1) Ticagrelor or Clopidogrel administered less than 12 hours from the symptoms onset. 2) greater than or equal to 12 hours from the symptoms onset

Full Information

First Posted
March 17, 2017
Last Updated
May 15, 2018
Sponsor
University of Sao Paulo General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03104062
Brief Title
Effect of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients With Acute Myocardial Infarction
Official Title
Effect of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients With Acute Myocardial Infarction
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
October 1, 2016 (Actual)
Primary Completion Date
February 1, 2018 (Actual)
Study Completion Date
February 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Of the patients diagnosed with ST-segment elevation myocardial infarction (STEMI) who underwent reperfusion therapy and have thrombolysis in myocardial infarction (TIMI) 3 flow, about 40% have flow alterations in the coronary microcirculation, which leads to worse remodeling of the left ventricle with a consequent increase in the mortality of this population. Clopidogrel is the only known antiplatelet medication that brings benefits to the coronary microcirculation. Ticagrelor is significantly superior to clopidogrel in terms of decreasing mortality. The main objective of this study is to compare the effect of ticagrelor versus clopidogrel on the coronary microcirculation by the Myocardial Perfusion Score Index (MPSI) obtained using Microbubble Contrasted Echocardiography (MCE) in patients who have STEMI and treated with thrombolysis.
Detailed Description
The present project should prospectively include patients participating in the TREAT study, who are including individuals with Acute Myocardial Infarction (AMI) treated with fibrinolytic and openly randomized to ticagrelor or clopidogrel within 24 hours of the onset of symptoms. Patients will be submitted to coronary angiography within 4 (± 2) days of the onset of symptoms, and those who, at the end of coronary angiography, present residual obstruction in the culprit vessel of less than 50% and have TIMI 3 flow, regardless of have undergone percutaneous coronary intervention will be included. Following, on day 2 (± 1) days after coronary angiography (therefore 6 ± 3 days from the onset of symptoms), they will be submitted to microcirculation perfusion evaluation by means of MPSI (myocardial perfusion score index) obtained by MCE (Microbubble contrasted echocardiography) - blood collection for evaluation of Platelet aggregability will be performed immediately prior to the start of MCE. Finally, in order to evaluate left ventricular remodeling, patients will undergo a new Echocardiography within 90 (± 10) days after discharge.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Microvascular Disease, Ticagrelor, Thrombolysis, Microbubble Contrasted Echocardiography

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ticagrelor
Arm Type
Other
Arm Description
Patients will be randomized to have Ticagrelor 90mg BID
Arm Title
Clopidogrel
Arm Type
Other
Arm Description
Patientes will be randomized to have Clopidogrel 75mg once a day
Intervention Type
Diagnostic Test
Intervention Name(s)
Microbubble Contrasted Echocardiography
Intervention Description
Myocardial Perfusion Score Index (MPSI) obtained using Microbubble Contrasted Echocardiography
Intervention Type
Diagnostic Test
Intervention Name(s)
Platelet Aggregability
Intervention Description
Obtained using Multiplate Analyzer
Intervention Type
Diagnostic Test
Intervention Name(s)
Laboratory
Intervention Description
it will be collected at patients arrival, Reative C-Protein, BNP, CK-mass, Troponine, interleukine-6, Creatinine.
Primary Outcome Measure Information:
Title
Myocardial Perfusion Score Index (MPSI)
Description
Obtained using Microbubble Contrasted Echocardiography
Time Frame
4 (±3) days after Cardiac catheterization
Secondary Outcome Measure Information:
Title
Left ventricular remodeling 90 days after de AMI, using Echocargiography parameters (End diastolic volume, end systolic volume and ejection Fraction)
Description
To compare the parameters of left ventricular remodeling (End diastolic volume, End Systolic Volume, Ejection Fraction) at after 90 days after discharge from the ticagrelor and clopidogrel groups
Time Frame
after 90 days after discharge
Title
number of myocardial segments with perfusion deficit in coronary microcirculation
Description
To evaluate the number of myocardial segments with perfusion deficit in coronary microcirculation in the ticagrelor and clopidogrel groups
Time Frame
4 (±3) days after Cardiac catheterization
Title
MPSI in patients submitted to angioplasty
Description
To evaluate MPSI in the subgroups of patients submitted to angioplasty and not submitted to angioplasty
Time Frame
4 (±3) days after Cardiac catheterization
Title
Patients who used clopidogrel prior to randomization and were randomized to ticagrelor
Description
To evaluate MPSI in subgroups of patients who used clopidogrel prior to randomization and were randomized to ticagrelor
Time Frame
4 (±3) days after Cardiac catheterization
Title
Elective versus Urgent Percutaneous Coronary Intervention (PCI)
Description
To compare the ticagrelor and clopidogrel groups in patients who had elective or urgent PCI
Time Frame
4 (±3) days after Cardiac catheterization
Title
Platelet aggregability
Description
To evaluate the platelet aggregability in the ticagrelor and clopidogrel groups obtained immediately before Myocardial Contrasted Echocardiography (MCE) by Multiplate
Time Frame
4 (±3) days after Cardiac catheterization
Title
Time Ticagrelor or Clopidogrel is administered
Description
Evaluate the main objective of the study in two subgroups: 1) Ticagrelor or Clopidogrel administered less than 12 hours from the symptoms onset. 2) greater than or equal to 12 hours from the symptoms onset
Time Frame
4 (±3) days after Cardiac catheterization
Other Pre-specified Outcome Measures:
Title
Laboratory analysis
Description
Number of Participants With Abnormal Laboratory Values in both groups, Ticagrelor and Clopidogrel. The laboratory analysis will be: Platelet count; Platelet mean volume; HbA1C; Creatinine clearance; Reactive c-protein; Interleucine-6; Brain natriuretic peptide (BNP); Troponin; Creatine Kinase-MB (CK-MB);
Time Frame
4 (±3) days after Cardiac catheterization
Title
In hospital use of morphine (Yes or No)
Description
Evaluate MPSI in patients who used Morphine or not.
Time Frame
4 (±3) days after Cardiac catheterization
Title
In hospital Use of Proton Pump Inhibitor (PPI) (yes or no)
Description
Evaluate MPSI in patients who used PPI or not
Time Frame
4 (±3) days after Cardiac catheterization

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: age from 18 years old to 75 years old. Patients with a ST-segment elevation AMI with up to 24 hours duration, documented by ischemic symptoms due to atherosclerosis> 10 minutes at rest, treated with pharmacological thrombolysis, acetylsalicylic acid (ASA) and Clopidogrel or Ticagrelor. Cardiac catheterization performed within 4 (± 2) days of the onset of symptoms, which at the end of coronary angiography showed residual obstruction in the "culprit" artery <50% with TIMI 3 flow regardless of whether or not the percutaneous coronary intervention was performed. Exclusion Criteria: Previous infarction known from the same wall as the current one Any contraindication to the use of Clopidogrel or Ticagrelor Need for oral anticoagulation therapy or aspirin doses greater than 100mg per day. Concomitant oral or intravenous therapy with strong inhibitors of Cytochrome P450, family 3, subfamily A (CYP3A), Substrates of CYP3A with narrow therapeutic indices or strong inducers of CYP3A High risk of bradyarrhythmias Dialysis therapy Clinically important thrombocytopenia known Clinically Significant Anemia Pregnancy or lactation Contraindications to fibrinolytic therapy
Facility Information:
Facility Name
Heart Institute (InCor) - University of Sao Paulo Medical School
City
Sao Paulo
ZIP/Postal Code
05403000
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35218519
Citation
Scanavini-Filho MA, Berwanger O, Matthias W, Aguiar MO, Chiang HP, Azevedo L, Baracioli LM, Lima FG, Furtado RHM, Dalcoquio TF, Menezes FR, Ferrari AG, de Luca F, Giugliano RP, Goodman S, Nicolau JC. Effects of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients with Acute Myocardial Infarction. Adv Ther. 2022 Apr;39(4):1832-1843. doi: 10.1007/s12325-022-02061-0. Epub 2022 Feb 26.
Results Reference
derived

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Effect of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients With Acute Myocardial Infarction

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