Different Platelet Activities Between Intracoronary and Peripheral Blood in Coronary Artery Disease Patients (DPABIAP)

Antiplatelet treatment is important for coronary artery disease(CAD) patients .Some patients are resistant to antiplatelet treatment based on platelet function tests(PFT).Currently the results of PFT are mainly based on the analysis of peripheral blood. instead, adverse cardiovascular events in CAD patients may be more directly related to platelet activities in the coronary arteries. There's no evidence of system study to prove the PFT of peripheral blood can represent the platelet functions in coronary arteries.The purpose of this study is to determine the different platelet activities in the blood of peripheral vein (PV), peripheral artery (PA), intracoronary artery (IC) in the CAD patients without or with different interventions.

our study is divided into three parts: Part A: To study the different platelet activities in the blood of PV, PA, IC in the CAD patients with dual antiplatelet therapy.

Part B: To explore the different platelet activities of the above three sites in ST-segment elevation myocardial infarction (STEMI) patients who are administrated platelet membrane glycoprotein Ⅱb/Ⅲa (GPⅡb/Ⅲa) receptor antagonist ( tirofiban ) in PV or IC and dual antiplatelet therapy.

Part C: To explore the different platelet activities of the above three sites in STEMI patients who are administrated antiplatelet thrombolysin or placebo in PV and dual antiplatelet therapy.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Clopidogrel; Drug: Aspirin; Drug: Clopidogrel; Drug: tirofiban in PV; Drug: tirofiban in IC; Drug: antiplatelet thrombolysin; Drug: placebo

Detailed Description

Part A:A total of 30 CAD patients are recruited.All patients are on loading dose of 300 mg clopidogrel followed by a maintenance dose of 75 mg/d for at least 5 days and a loading dose of 300 mg aspirin followed by a maintenance dose of 100 mg/d for at least 5 days. All patients plan to receive coronary arteriography (CAG) or percutaneous coronary intervention (PCI).The investigators sample blood from PV,PA and IC before PCI.Regional differences will be compared between blood samples from PV,PA and IC by light aggregometry (agonists: arachidonic acid, LTA-AA; adenosine diphosphat, LTA-ADP), VerifyNow P2Y12 assays. Differences between LTA and VerifyNow P2Y12-assay will also be compared.

Part B:A total of 30 STEMI patients are recruited.Patients are randomly assigned to 2 groups.A group(n=15) is given tirofiban through PV, the other group(n=15) is given through IC.All patients are on loading dose of 600 mg clopidogrel and 300 mg aspirin.All patients plan to receive emergency PCI. Group PV: a loading dose of 10ug/kg tirofiban is given in 3 min through PV,followed by a maintenance dose of 0.15ug/kg*min for 48h.Group IC: a loading dose of 10ug/kg tirofiban is given through IC,followed by a maintenance dose of 0.15ug/kg*min for 48h. Blood samples are collceted from PV, PA and IC before the injection of loading dose tirofiban , and 15min after the injection.Regional differences will be compared between blood samples from PV,PA and IC by LTA-AA; LTA-ADP, LTA-RIS(agonists:ristocetin),VerifyNow P2Y12 assays.

Part C:A total of 30 STEMI patients are recruited.Patients are randomly assigned to 2 groups.A group(n=15) is given antiplatelet thrombolysin(the frist antiplatelet drugs based on GP Ib receptor which completed the preclinical and phase I clinical studies,and already has entered phase II clinical studies) through PV, the other group(n=15) is given placebo through PV.All patients are on loading dose of 600 mg clopidogrel and 300 mg aspirin.All patients plan to receive emergency PCI.Both Groups are given in the same way , a loading dose of 5 IU/60kg in 5 min through PV,followed by a maintenance dose of 0.002 IU/kg/h for 48h. Blood samples are collceted from PV, PA and IC before the injection of loading dose of antiplatelet thrombolysin or placebo, and 15 min after the injection.Regional differences will be compared between blood samples from PV,PA and IC by LTA-AA; LTA-ADP, LTA-RIS and VerifyNow P2Y12 assays.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • First Affiliated Hospital of Nanjing Medical University
      • Sub-Investigator: Dingguo Zhang, Ph.D

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. CAD patients plan to receive coronary arteriography (CAG) or percutaneous coronary intervention (PCI).
2. Patient aged >18 years and ≦75 years old;
3. Signed inform consent

Exclusion Criteria:

1. Allergy or intolerance to ASA, clopidogrel , tirofiban ,antiplatelet thrombolysin;
2. Subjects at a high risk of bleeding (e.g. platelet count< 100*109/L, known bleeding diathesis , active peptic ulcer );
3. Patients who are planning to take warfarin or drugs that potentially could interfere with the anti-platelet effects .
4. severe hemodynamic instability
5. severe liver and renal dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: dual antiplatelet therapy; clopidogrel +aspirin	Drug: Clopidogrel; loading dose of 300 mg clopidogrel followed by a maintenance dose of 75 mg/d for at least 5 days; Drug: Aspirin; loading dose of 300 mg aspirin followed by a maintenance dose of 100 mg/d for at least 5 days.; Drug: Clopidogrel; loading dose of 600 mg clopidogrel followed by a maintenance dose of 75 mg/d for at least 5 days
EXPERIMENTAL: tirofiban in PV; clopidogrel +aspirin + tirofiban in PV	Drug: Clopidogrel; loading dose of 300 mg clopidogrel followed by a maintenance dose of 75 mg/d for at least 5 days; Drug: Aspirin; loading dose of 300 mg aspirin followed by a maintenance dose of 100 mg/d for at least 5 days.; Drug: Clopidogrel; loading dose of 600 mg clopidogrel followed by a maintenance dose of 75 mg/d for at least 5 days; Drug: tirofiban in PV; a loading dose of 10ug/kg tirofiban is given in 3 min through PV,followed by a maintenance dose of 0.15ug/kg*min for 48h. (clopidogrel 600 mg+aspirin( ASA) 300 mg)x1 day.; Other Names: GPⅡb/Ⅲa receptor antagonist
EXPERIMENTAL: tirofiban in IC; clopidogrel +aspirin +tirofiban in IC	Drug: Clopidogrel; loading dose of 300 mg clopidogrel followed by a maintenance dose of 75 mg/d for at least 5 days; Drug: Aspirin; loading dose of 300 mg aspirin followed by a maintenance dose of 100 mg/d for at least 5 days.; Drug: Clopidogrel; loading dose of 600 mg clopidogrel followed by a maintenance dose of 75 mg/d for at least 5 days; Drug: tirofiban in IC; a loading dose of 10ug/kg tirofiban is given in 3 min through IC,followed by a maintenance dose of 0.15ug/kg*min for 48h. (clopidogrel 600 mg+ ASA 300 mg)x1 day.; Other Names: GP IIb/IIIa receptor antagonist
EXPERIMENTAL: antiplatelet thrombolysin; clopidogrel +aspirin +antiplatelet thrombolysin	Drug: Clopidogrel; loading dose of 300 mg clopidogrel followed by a maintenance dose of 75 mg/d for at least 5 days; Drug: Aspirin; loading dose of 300 mg aspirin followed by a maintenance dose of 100 mg/d for at least 5 days.; Drug: Clopidogrel; loading dose of 600 mg clopidogrel followed by a maintenance dose of 75 mg/d for at least 5 days; Drug: antiplatelet thrombolysin; a loading dose of 5 IU/60kg in 5 min through PV,followed by a maintenance dose of 0.002 IU/kg/h for 48h. (clopidogrel 600 mg+ ASA 300 mg)x1 day.; Other Names: GP Ib receptor antagonist
PLACEBO_COMPARATOR: placebo; clopidogrel +aspirin +placebo	Drug: Clopidogrel; loading dose of 300 mg clopidogrel followed by a maintenance dose of 75 mg/d for at least 5 days; Drug: Aspirin; loading dose of 300 mg aspirin followed by a maintenance dose of 100 mg/d for at least 5 days.; Drug: Clopidogrel; loading dose of 600 mg clopidogrel followed by a maintenance dose of 75 mg/d for at least 5 days; Drug: placebo; a loading dose of 5 IU/60kg in 5 min through PV,followed by a maintenance dose of 0.002 IU/kg/h for 48h. (clopidogrel 600 mg+ ASA 300 mg)x1 day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
platelet aggregation	Regional differences between blood samples from PV,PA and IC by LTA and VerifyNow P2Y12 assays.The results of LTA are reported in platelet aggregation rate（%）.Platelet aggregation was induced using 0.5 mg/ml arachidonic acid (AA) and 5 μmol/l ADP.The maximum aggregation achieved during an 8-minute period was used for analysis.The results of the VerifyNow P2Y12-assay are reported in P2Y12 reaction units (PRU).(using 20 μmol/l ADP as the agonist and 22 nmol/l prostag- landin E1 (PGE1). a value that uses iso- thrombin receptor-activating peptide to approximate a baseline off-drug platelet reactivity value, and percentage inhibition.	2 hours

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: National Natural Science Foundation of China

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2016
• Primary Completion (ANTICIPATED): November 1, 2017
• Study Completion (ANTICIPATED): December 1, 2017

Study Registration Dates

• First Submitted: February 23, 2017
• First Submitted That Met QC Criteria: March 7, 2017
• First Posted (ACTUAL): March 13, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 13, 2017
• Last Update Submitted That Met QC Criteria: March 7, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: tirofiban; Platelet Activities; light aggregometry; VerifyNow P2Y12-assay; peripheral vein; peripheral artery; intracoronary artery; antiplatelet thrombolysin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; 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; Aspirin; Clopidogrel; Tirofiban; Fibrinolysin
• Other Study ID Numbers: 005