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

Coronary Microvascular Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03104062
• Other study ID #: 4416
• Status: Completed
• Phase: N/A
• Start date: October 1, 2016
• Est. completion date: February 1, 2018

Study information

• Verified date: May 2018
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: February 1, 2018
• Est. primary completion date: February 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Microvascular Disease
• Infarction
• Microbubble Contrasted Echocardiography
• Myocardial Infarction
• Thrombolysis
• Ticagrelor

Intervention

Diagnostic Test:
• Microbubble Contrasted Echocardiography
Myocardial Perfusion Score Index (MPSI) obtained using Microbubble Contrasted Echocardiography
• Platelet Aggregability
Obtained using Multiplate Analyzer
• Laboratory
it will be collected at patients arrival, Reative C-Protein, BNP, CK-mass, Troponine, interleukine-6, Creatinine.

Locations

Country	Name	City	State
Brazil	Heart Institute (InCor) - University of Sao Paulo Medical School	Sao Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Laboratory analysis	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);	4 (±3) days after Cardiac catheterization
Other	In hospital use of morphine (Yes or No)	Evaluate MPSI in patients who used Morphine or not.	4 (±3) days after Cardiac catheterization
Other	In hospital Use of Proton Pump Inhibitor (PPI) (yes or no)	Evaluate MPSI in patients who used PPI or not	4 (±3) days after Cardiac catheterization
Primary	Myocardial Perfusion Score Index (MPSI)	Obtained using Microbubble Contrasted Echocardiography	4 (±3) days after Cardiac catheterization
Secondary	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	after 90 days after discharge
Secondary	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	4 (±3) days after Cardiac catheterization
Secondary	MPSI in patients submitted to angioplasty	To evaluate MPSI in the subgroups of patients submitted to angioplasty and not submitted to angioplasty	4 (±3) days after Cardiac catheterization
Secondary	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	4 (±3) days after Cardiac catheterization
Secondary	Elective versus Urgent Percutaneous Coronary Intervention (PCI)	To compare the ticagrelor and clopidogrel groups in patients who had elective or urgent PCI	4 (±3) days after Cardiac catheterization
Secondary	Platelet aggregability	To evaluate the platelet aggregability in the ticagrelor and clopidogrel groups obtained immediately before Myocardial Contrasted Echocardiography (MCE) by Multiplate	4 (±3) days after Cardiac catheterization
Secondary	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	4 (±3) days after Cardiac catheterization