Efficacy of Ticagrelor vs Clopidogrel in High-risk NSTE-ACS Patients Undergoing Early PCI

NCT02201667 | Unknown Phase 4 DMC

• 1 other identifier: ISSBRIL0208
• Study Type: interventional
• Target: 444
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Coronary Syndrome

Keywords

non-ST elevation acute coronary syndrome; myocardial perfusion; magnetic Resonance Imaging; antiplatelet

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Cardiac Magnetic Resonance Imaging

  At 30th day after randomization

• Echocardiography

  At 30th day after randomization

• Myocardial-specific isoenzyme of creatine kinase (CK-MB) enzyme levels peri-PCI

  Within 0 to 48 hours after enrollment

Other Outcomes (2)

• Bleeding events: Incidence of bleeding events

  Within 0 to 30 dys after randomization

• Other adverse events

  Within 0 to 30 days after randomization

Study Arms (2)

Ticagrelor group

EXPERIMENTAL

Patients wil be given 180 mg loading dose of ticagrelor and 300mg loading dose of aspirin followed by PCI, then will receive 90 mg ticagrelor twice daily with aspirin maintenance dose to 30 days after randomization.

Drug: Ticagrelor; Drug: Aspirin; Procedure: PCI

Clopidogrel group

ACTIVE COMPARATOR

Patients will be given clopidogrel 300mg loading dose and 300mg loading dose of aspirin followed by PCI, then will receive 75mg clopidogrel once with aspirin maintenance dose to 30 days after randomization.

Drug: clopidogrel; Drug: Aspirin; Procedure: PCI

Interventions

Ticagrelor DRUG

180-mg loading dose followed by 90mg twice daily for 30 days

Also known as: BRILINTA

Ticagrelor group

clopidogrel DRUG

300-mg loading dose followed by 75mg once daily for 30 days.

Also known as: Plavix

Clopidogrel group

Aspirin DRUG

300mg loading dose aspirin and followed by 100mg once daily

Also known as: Aspirin Enteric Coated Tablets

Clopidogrel group; Ticagrelor group

PCI PROCEDURE

PCI is performed according to indication for early PCI according to 2012 Chinese NSTE-ACS guideline recommendation

Clopidogrel group; Ticagrelor group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures;
• 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;
• 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.

You may not qualify if:

• Evidence of cardiac rupture;
• History of major hemorrhage (intracranial, gastrointestinal, etc.);
• Active pathological bleeding;
• Acute or chronic hematologic disorder including a Hemoglobin less than 10 g/L or a platelet count less than 10×109/L before procedure;
• Contraindication against the use of clopidogrel and ticagrelor;
• 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.
• 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;
• 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);
• Previous enrolment in this study or treatment with an investigational drug or device under another study protocol in the past 30 days;
• Treatment with anticoagulants;
• Pregnancy or lactating;
• Body weight \<40kg or \>125kg;
• Known hypersensitivity to any drug that may appear in the study;
• 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;

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Ren Ji Hospital Afflited to School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, 200127, China

Location

Related Publications (11)

• 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.

  PMID: 19960517 BACKGROUND

• 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.

  PMID: 19923168 BACKGROUND

• 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. doi: 10.1161/01.cir.101.2.125.

  PMID: 10637197 BACKGROUND

• 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. doi: 10.1161/01.cir.97.23.2302.

  PMID: 9639373 BACKGROUND

• 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. No abstract available. Chinese.

  PMID: 22883082 BACKGROUND

• 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(1):58. doi: 10.1186/1532-429X-15-58.

  PMID: 23806080 BACKGROUND

• 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. doi: 10.1016/s0735-1097(00)01101-3.

  PMID: 11153779 BACKGROUND

• 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.

  PMID: 21176835 BACKGROUND

• 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: 10.1007/BF03337726. Epub 2009 Dec 1.

  PMID: 20009495 BACKGROUND

• 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. No abstract available.

  PMID: 21670242 BACKGROUND

• 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.

  PMID: 22094974 BACKGROUND

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Ticagrelor; Clopidogrel; Aspirin

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Ben He, MD,PhD

  Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ben He, MD,PhD

CONTACT

68383609; heben1025@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2014
• First Posted: July 28, 2014
• Study Start: August 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: October 1, 2016
• Last Updated: August 4, 2014

Record last verified: 2014-07

Locations

CN (1)