Ticagrelor and Clopidogrel on Reperfusion in Patients With AMI

NCT ID: NCT02233790

Last Updated: 2014-09-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2016-12-31

Brief Summary

The patients with acute myocardial infarction (AMI) present high mortality and morbidity rate,even treated with stenting in the blocked heart vessels.

The appearance of no-reflow is common after re-opening of the blocked vessel. The no-reflow were commonly attributed to tiny blockage in coronary micro-vasculature by thrombus and spasm of the micro-vessel during stenting.

An agent with more effective anti-clotting and micro-vessel dilation would be helpful to solve the issue of no-reflow. Ticagrelor was demonstrated to be a potent platelet inhibitor and a potent micro-vessel dilator which can influence metabolism of adenosine, a endogenous potent small vessel dilator.

This study is to test the effectiveness of ticagrelor on improving reperfusion and minimizing the myocardial infarct size after PPCI in patients with AMI.

Detailed Description

The patients with acute myocardial infarction (AMI) present high mortality and morbidity rate, and also have malignant prognosis even if they could survive. The mortality and prognosis has been improved markedly because of the treatment with primary percutaneous coronary intervention (PPCI). However, the issue of no-reflow after revascularization has not been solved yet. The mechanisms of no-reflow in human being were regarded mainly as micro-embolism in coronary micro-circulation with thrombus or debris from atherosclerotic plaque, coronary micro-vasculature spasm and other conditions.

Therefore, an agent with potent antithrombotic and micro-vasculature dilation function would be more effective on prevention of no-reflow after coronary revascularization. Ticagrelor was demonstrated to be a potent platelet inhibitor and a potent micro-vessel dilator which can influence metabolism of adenosine.

Ticagrelor can inhibit adenosine uptake in vitro and subsequently augments cardiac blood flow in a canine model of reactive hypoxia- or adenosine-induced blood flow increases. In a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion. These findings suggest that ticagrelor may have additional benefits in patients with acute coronary syndrome beyond inhibition of platelet aggregation, which is advantageous to the dilation of microcirculation and improvement of myocardial perfusion. AMISTAD study shows that: adenosine reperfusion therapy can reduce 33% of the infarction area assessed by single-photon emission computed tomography (SPECT) detection. AMISTAD- 2 study showed that: adenosine early reperfusion therapy can reduce the composite end point of death and heart failure events. Additionally, ticagrelor is a non-precursor agent, playing a role directly on platelet inhibition.

Myocardial perfusion imaging with SPECT is among the most widely used and well-established noninvasive tools for the diagnosis of ischemic coronary disease. It has been shown to have a high sensitivity and specificity in identifying patients with coronary artery disease and to be accurate in identifying areas of prior myocardial infarction.

Given the evidence (from PLATO trial) of greater IPA with ticagrelor than clopidogrel, similar risk of major bleeding and probable effect of micro-vasculature dilation due to adenosine, ticagrelor will improve the reperfusion and decrease the infarct size significantly.

This study is to test the effectiveness of ticagrelor on improving reperfusion and minimizing the myocardial infarct size after PPCI in patients with AMI. Also, it is to evaluate the safety of ticagrelor in patients with AMI.

Conditions

Myocardial Infarction; No-Reflow Phenomenon

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ticagrelor

Group Type: EXPERIMENTAL

Ticagrelor

Intervention Type: DRUG

a loading dose of 180mg pre-PCI, and then 90 mg twice daily for 1 Month within the study. Thereafter, the patients will take clopidogrel if Ticagrelor is not available on the market.

Clopidogrel

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

Clopidogrel 75 mg once daily after a loading dose of 300 mg pre-PCI.

Interventions

Ticagrelor

a loading dose of 180mg pre-PCI, and then 90 mg twice daily for 1 Month within the study. Thereafter, the patients will take clopidogrel if Ticagrelor is not available on the market.

Intervention Type: DRUG

Clopidogrel

Clopidogrel 75 mg once daily after a loading dose of 300 mg pre-PCI.

Intervention Type: DRUG

Other Intervention Names

Brilinta; Plavix

Eligibility Criteria

Inclusion Criteria

• Provision of informed consent prior to any study specific procedures
• Patients with acute ST-segment elevation myocardial infarction, an onset of symptoms presented within 12 hours. Two criteria have to be met: persistent ST-segment elevation of at least 0.1 mV in at least two contiguous leads or a new left bundle-branch block, and the intention to perform primary PCI
• Patients must agree to undergo all protocol-required follow-up examinations and not to participate any other clinical trials within the duration of this study

Exclusion Criteria

• Any contraindication against the use of clopidogrel or ticagrelor
• Fibrinolytic therapy within 24 hours before randomization
• Stroke within the previous 6 months or intracranial hemorrhage at any time before randomization
• Any other concomitant severe organic or systemic disorder, such as severe liver (ALT>3×ULN )or renal disease(creatinin>5.0mg/dl or 442μmol/L), etc.
• A need for oral anticoagulation therapy
• An increased risk of bradycardia or atrial-ventricle block
• Concomitant therapy with a strong cytochrome P-450 3A inhibitor or inducer
• Pregnant women or breast-feeding, or planning to become pregnant while enrolled in this study
• Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

First Hospital of China Medical University

OTHER

Sponsor Role: lead

Responsible Party

Yingxian Sun

Director, Department of cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yingxian Sun, Dr.

Role: PRINCIPAL_INVESTIGATOR

First Hospital of China Medical University

Locations

The First Hospital of China Medical University

Shenyang, Liaoning, China

Countries

China

Central Contacts

Yingxian Sun, Dr.

Role: CONTACT

sunyingxian12@126.com

0086-24-83282688

Wen Tian, Dr.

Role: CONTACT

dr.wentian@gmail.com

0086-24-83282300

Facility Contacts

Jianhua Tong, Master

Role: primary

yykyk@vip.163.com

0086-24-83282837

References

Mahaffey KW, Puma JA, Barbagelata NA, DiCarli MF, Leesar MA, Browne KF, Eisenberg PR, Bolli R, Casas AC, Molina-Viamonte V, Orlandi C, Blevins R, Gibbons RJ, Califf RM, Granger CB. Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial. J Am Coll Cardiol. 1999 Nov 15;34(6):1711-20. doi: 10.1016/s0735-1097(99)00418-0.

Reference Type: BACKGROUND

PMID: 10577561 (View on PubMed)

Steg PG, James S, Harrington RA, Ardissino D, Becker RC, Cannon CP, Emanuelsson H, Finkelstein A, Husted S, Katus H, Kilhamn J, Olofsson S, Storey RF, Weaver WD, Wallentin L; PLATO Study Group. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: A Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation. 2010 Nov 23;122(21):2131-41. doi: 10.1161/CIRCULATIONAHA.109.927582. Epub 2010 Nov 8.

Reference Type: BACKGROUND

PMID: 21060072 (View on PubMed)

Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. doi: 10.1161/CIRCULATIONAHA.109.912550. Epub 2009 Nov 18.

Reference Type: BACKGROUND

PMID: 19923168 (View on PubMed)

Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW; AMISTAD-II Investigators. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol. 2005 Jun 7;45(11):1775-80. doi: 10.1016/j.jacc.2005.02.061.

Reference Type: BACKGROUND

PMID: 15936605 (View on PubMed)

Other Identifiers

ISSBRIL0209

Identifier Type: -

Identifier Source: org_study_id