Acute Coronary Syndrome Clinical Trial
Official title:
An Open-label Study Evaluating the Acute Efficacy of Treatment With Ticagrelor Versus Clopidogrel on Myocardial Tissue-level Perfusion Assessed by TMPFC and MRI in Patients With High-risk NSTE-ACS Undergoing Early PCI(EARLY-MYO II)
The goal of acute coronary syndrome (ACS) therapy is to successfully restore both epicardial
blood flow and myocardial perfusion. Percutaneous coronary intervention (PCI) has been
documented as being the most effective method for restoration of epicardial blood flow.
However, epicardial blood flow does not necessarily equate to myocardial perfusion.
Clopidogrel binds irreversibly to platelet P 2 Y 12 receptors to inhibit platelet
aggregation, with main limitations of slow onset, prevention of recovery of platelet
functions, and interindividual variability. Clinical pharmacology and early dose-finding
studies suggested a faster onset and greater and more consistent inhibition of platelet
aggregation (IPA) with ticagrelor compared with clopidogrel. Two currently main methods of
angiographic assessment of myocardial perfusion includes thrombolysis in myocardial
infarction(TIMI) myocardial perfusion grading (TMPG) and myocardial blush grading (MBG).
These established myocardial perfusion parameters have been widely used in various important
trials and are reported to be highly useful in predicting clinical outcomes. However, visual
assessment of these methods is categorical, subjective, and operator dependent of contrast
in the myocardium using cine-angiographic frame-counting, was developed by the
investigators' center to quantify myocardial tissue- level perfusion and was proved to be a
predictive value on clinical prognosis.
Thus, the investigators aim to initiate an open-label study evaluating the acute efficacy of
treatment with ticagrelor versus clopidogrel on myocardial tissue-level perfusion assessed
by Myocardial Perfusion Frame Count(TMPFC) and magnetic resonance imaging (MRI) in patients
with high-risk non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing early
percutaneous coronary intervention (PCI) .
The investigators hypothesize that compared with clopidogrel, ticagrelor can significantly
improve myocardial perfusion assessed by Myocardial Perfusion Frame Count(TMPFC) in
high-risk non-ST elevation acute coronary syndrome (NSTE-ACS) patients undergoing early
percutaneous coronary intervention (PCI), without additional increased major bleeding.
Status | Not yet recruiting |
Enrollment | 444 |
Est. completion date | October 2016 |
Est. primary completion date | August 2016 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: For inclusion in the study subjects should fulfill the following criteria: 1. Provision of informed consent prior to any study specific procedures; 2. Men or women > 18 years of age, with documented evidence of non-ST segment elevation Acute Coronary Syndrome(ACS) in the 24 hours before randomisation; 3. Hospitalized for high-risk non-ST segment elevation Acute Coronary Syndrome(ACS)(GRACE risk score>140) with indication for early percutaneous coronary intervention (PCI) according to 2012 Chinese non-S T segment elevation Acute Coronary Syndrome(ACS) guideline recommendation. Exclusion Criteria: Subjects should not enter the study if any of the following exclusion criteria are fulfilled: 1. Evidence of cardiac rupture; 2. History of major hemorrhage (intracranial, gastrointestinal, etc.); 3. Active pathological bleeding; 4. Acute or chronic hematologic disorder including a Hemoglobin less than 10 g/L or a platelet count less than 10×109/L before procedure; 5. Contraindication against the use of clopidogrel and ticagrelor; 6. 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. 7. Severe complication 7.1 Other diseases with life expectancy =12 months; 7.2 Any history of Severe renal or hepatic dysfunction(hepatic failure, cirrhosis, portal hypertension and active hepatitis); Neutropenia, thrombocytopenia ; Known acute pancreatitis; 7.3 Arterial aneurysm, arterial/venous malformation and aorta dissection; 8. Complex heart condition 8.1 PCI within previous 1 month or Previous coronary-artery bypass surgery(CABG); 8.2 History of myocardial infarction; 8.3 Previously known multivessel coronary artery disease not suitable for percutaneous coronary intervention (PCI); 9. Previous enrolment in this study or treatment with an investigational drug or device under another study protocol in the past 30 days; 10. Treatment with anticoagulants; 11. Pregnancy or lactating; 12. Body weight <40kg or >125kg; 13. Known hypersensitivity to any drug that may appear in the study; 14. Inability to follow the protocol and comply with follow-up requirements or any other reason that the investigator feels would place the patient at increased risk; |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
China | Ren Ji Hospital Afflited to School of Medicine, Shanghai Jiao Tong University | Shanghai | Shanghai |
Lead Sponsor | Collaborator |
---|---|
RenJi Hospital |
China,
Chinese Society of Cardiology of Chinese Medical Association; Editorial Board of Chinese Journal of Cardiology. [Guideline of non-ST segment elevation acute coronary syndrome]. Zhonghua Xin Xue Guan Bing Za Zhi. 2012 May;40(5):353-67. Chinese. — View Citation
Ding S, Pu J, Qiao ZQ, Shan P, Song W, Du Y, Shen JY, Jin SX, Sun Y, Shen L, Lim YL, He B. TIMI myocardial perfusion frame count: a new method to assess myocardial perfusion and its predictive value for short-term prognosis. Catheter Cardiovasc Interv. 2010 Apr 1;75(5):722-32. doi: 10.1002/ccd.22298. — View Citation
Gibson CM, Cannon CP, Murphy SA, Ryan KA, Mesley R, Marble SJ, McCabe CH, Van De Werf F, Braunwald E. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation. 2000 Jan 18;101(2):125-30. — View Citation
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. — View Citation
Kidambi A, Mather AN, Motwani M, Swoboda P, Uddin A, Greenwood JP, Plein S. The effect of microvascular obstruction and intramyocardial hemorrhage on contractile recovery in reperfused myocardial infarction: insights from cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2013 Jun 27;15:58. doi: 10.1186/1532-429X-15-58. — View Citation
Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. — View Citation
Pu J, Ding S, Shan P, Qiao Z, Song W, Du Y, Shen J, Jin S, He B. Comparison of epicardial and myocardial perfusions after primary coronary angioplasty for ST-elevation myocardial infarction in patients under and over 75 years of age. Aging Clin Exp Res. 2010 Aug;22(4):295-302. doi: 10.3275/6711. Epub 2009 Dec 1. — View Citation
Pu J, Shan P, Ding S, Qiao Z, Jiang L, Song W, Du Y, Shen J, Shen L, Jin S, He B. Gender differences in epicardial and tissue-level reperfusion in patients undergoing primary angioplasty for acute myocardial infarction. Atherosclerosis. 2011 Mar;215(1):203-8. doi: 10.1016/j.atherosclerosis.2010.11.019. Epub 2010 Nov 26. — View Citation
Roe MT, Ohman EM, Maas AC, Christenson RH, Mahaffey KW, Granger CB, Harrington RA, Califf RM, Krucoff MW. Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion. J Am Coll Cardiol. 2001 Jan;37(1):9-18. Review. — View Citation
Shen LH, Wan F, Shen L, Ding S, Gong XR, Qiao ZQ, Du YP, Song W, Shen JY, Jin SX, Pu J, Yao TB, Jiang LS, Li WZ, Zhou GW, Liu SW, Han YL, He B. Pharmacoinvasive therapy for ST elevation myocardial infarction in China: a pilot study. J Thromb Thrombolysis. 2012 Jan;33(1):101-8. doi: 10.1007/s11239-011-0657-7. — View Citation
van 't Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra F. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Zwolle Myocardial Infarction Study Group. Circulation. 1998 Jun 16;97(23):2302-6. — View Citation
* Note: There are 11 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Bleeding events: Incidence of bleeding events | Incidence of bleeding events, classified by TIMI criteria and GUSTO severity criteria. | Within 0 to 30 dys after randomization | Yes |
Other | Other adverse events | Including any other adverse events (AEs) during the study. | Within 0 to 30 days after randomization | Yes |
Primary | TIMI Myocardial Perfusion Frame Count (TMPFC) | The Myocardial Perfusion Frame Count (TMPFC) is developed to standardize and quantify myocardial perfusion by timing the filling and clearance of contrast in the myocardium using cine-angiographic frame-counting. The first frame of Myocardial Perfusion Frame Count (TMPFC) is defined as the frame that clearly demonstrates the first appearance of myocardial blush beyond the infarct-related artery (IRA) (F1). The last frame of Myocardial Perfusion Frame Count (TMPFC) is then defined as the frame where contrast or myocardial blush disappears (F2). TMPFC is therefore F2-F1 frame counts at filming rate of 15frames/sec. | Within 0 to 24 hours after randomization | No |
Secondary | Cardiac Magnetic Resonance Imaging | Cardiovascular MRI will be performed at 30th day, to detect microvascular obstruction (MO) and intramyocardial hemorrhage (IMH). Infarct size and myocardial strain will also be measured by the method previously described. | At 30th day after randomization | No |
Secondary | Echocardiography | echocardiography will be performed within 24h post PCI and at 30th day to assess changes in left ventricular size and function | At 30th day after randomization | No |
Secondary | Myocardial-specific isoenzyme of creatine kinase (CK-MB) enzyme levels peri-PCI | Infarct size is measured by the myocardial-specific isoenzyme of creatine kinase (CK-MB) area under the curve, calculated by the linear-trapezoidal method. If the baseline or last value is missing, the corresponding value will be set to zero. For missing values of intermediate time points, linear interpolation is used. | Within 0 to 48 hours after enrollment | No |
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