Clopidogrel Response Evaluation and AnTi-Platelet InterVEntion in High Thrombotic Risk PCI Patients (CREATIVE)

Investigator Initiated Prospective Study to Investigate the Best Anti-platelet Treatment in High Thrombotic Risk PCI Patients.

To identify the high-risk patients who might have in-stent thrombosis after PCI with thromboelastography and to head-to-head compare two intensified antiplatelet therapeutic strategies of double-dosage Clopidogrel and triple antiplatelet therapy with Cilostazol with the standard antiplatelet therapy.

Study Overview

• Status: Completed
• Conditions: Coronary Heart Disease
• Intervention / Treatment: Drug: Clopidogrel 75mg; Drug: Aspirin 100mg; Drug: Clopidogrel 150mg; Drug: Cilostazol 100mg

Detailed Description

Study population: Age 18 - 75, male or non-pregnant female; stable or unstable angina with evidence of myocardial ischemia, or patient with myocardial infarction; coronary angiography reveals stenosis lesions; discovery of ADP induced platelet inhibition rate < 50% and MAADP > 47mm via thromboelastography (indicating low responsiveness to Clopidogrel with high risk for stent thrombosis formation); is able to understand the objective of the trial, takes part voluntarily and signs the written informed consent form.

• Study Type: Interventional
• Enrollment (Actual): 1078
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Fuwai Cardiovascular Hospital
  • Beijing, China, 100037
    • Fuwai Cardiovascular Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 - 75, male or non-pregnant female;
2. Stable or unstable angina with evidence of myocardial ischemia, or patient with myocardial infarction;
3. Coronary angiography reveals stenosis lesions;
4. Discovery of ADP induced platelet inhibition rate < 50% and MAADP >47mm via thromboelastography (indicating low responsiveness to Clopidogrel with high risk for stent thrombosis formation);
5. Is able to understand the objective of the trial, takes part voluntarily and signs the written informed consent form.

Exclusion Criteria:

1. Those who have participated in other drug or therapy equipment clinical trials but did not reach the main study endpoint time limit;
2. Symptoms of severe heart failure (NYHA Class III and above) or left ventricular ejection fraction < 40% (ultrasound or left ventricle ngiography);
3. Pregnant or lactating women;
4. severely impaired renal function before surgery: serum creatinine > 2.0mg/dl;
5. Impaired liver function before surgery: Serum GPT > 120U/L;
6. Bleeding tendency, history of active peptic ulcer, history of cerebral hemorrhage or cavum subarachnoidale bleeding, patients with antiplatelet agent and anticoagulant treatment contraindications and hence are unable to undergo anticoagulant therapy;
7. Patients who are unable to withstand dual antiplatelet therapy due to allergy to Aspirin, Clopidogrel or ticlopidine, heparin, contrast agent, paclitaxel and metals;
8. Leucocyte < 3.5 x 109; and/or platelet < 100,000/mm3 or > 750,000/mm3;
9. Patient's life expectancy is less than 12 months;
10. Patients who plan to undergo coronary artery bypass grafting or other surgery within 1 year;
11. Those waiting for heart transplant;
12. Patients who are deemed by the researchers to have low compliance and unable to abide by the requirements and complete the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clopidogrel + Aspirit; A Standard antiplatelet therapy control group： Clopidogrel 75mg Qd + Aspirin 100mg Qd	Drug: Clopidogrel 75mg; Drug: Aspirin 100mg
Active Comparator: Clopidogrel + Aspirin; B Double-dosage Clopidogrel group： Clopidogrel 150mg Qd + Aspirin 100mg Qd	Drug: Aspirin 100mg; Drug: Clopidogrel 150mg
Active Comparator: Clopidogrel + Aspirin + Cilostazol; C triple antiplatelet therapy group： Cilostazol 100mg Bid + Aspirin 100mg Qd + Clopidogrel 75mg Qd	Drug: Clopidogrel 75mg; Drug: Aspirin 100mg; Drug: Cilostazol 100mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiac and cerebrovascular events	MACCE, including cardiac death, myocardial infarction, target vessel revascularization and cerebrovascular events	within 1.5years of patient enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary endpoint	Occurrence of stent thrombosis	within 1.5 years of patients enrolled
bleeding	Major bleeding and minor bleeding	within 1.5 years of patients' enrolled
quality of life of patient	to evaluate with Seattle Angina Scale	within 1.5 years of patients' enrolled

Collaborators and Investigators

• Sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
• Collaborators: Zhejiang Otsuka Pharmaceutical Co., Ltd.; Haemonetics Corporation; Beijing Municipal Health Bureau
• Investigators: Study Chair: Yuejin Yang, PHD, FuWai Hospital, CAMS & PUMC

Publications and helpful links

General Publications

• Tang YD, Wang W, Yang M, Zhang K, Chen J, Qiao S, Yan H, Wu Y, Huang X, Xu B, Gao R, Yang Y; CREATIVE Investigators. Randomized Comparisons of Double-Dose Clopidogrel or Adjunctive Cilostazol Versus Standard Dual Antiplatelet in Patients With High Posttreatment Platelet Reactivity: Results of the CREATIVE Trial. Circulation. 2018 May 22;137(21):2231-2245. doi: 10.1161/CIRCULATIONAHA.117.030190. Epub 2018 Feb 2.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: January 15, 2013
• First Submitted That Met QC Criteria: January 28, 2013
• First Posted (Estimate): January 30, 2013

Study Record Updates

• Last Update Posted (Actual): July 19, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: PCI; clopidogrel; cilostazol; Thrombelastography; platelet function monitoring; in-stent thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neuroprotective Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Aspirin; Clopidogrel; Cilostazol
• Other Study ID Numbers: 2011-4003-03