Platelet Inhibition in the Acute Phase of STEMI

NCT01144819 | Completed

• 1 other identifier: 23374
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Dual antithrombotic treatment with aspirin and clopidogrel is recommended in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The European Society of Cardiology (ESC) Guidelines recommend a bolus dose of aspirin of 250-500 mg and a 600 mg bolus dose of clopidogrel as soon as STEMI is suspected. Studies have shown that more newly produced platelets are present in the acute phase of STEMI, and it is likely that these immature platelets are haemostatically more active and might be of importance in thrombus formation. The enhanced platelet reactivity may reduce the effect of aspirin and clopidogrel in the acute phase of STEMI compared to measurements made in the same patients 3 months after primary PCI. Aim: This study aims to compare platelet response to aspirin and clopidogrel in the acute phase of STEMI with the platelet response in the same patients 3 months after STEMI . Design: This study is an observational follow-up study. Materials and methods: 46 patients with STEMI referred to primary PCI at Aarhus University Hospital, Skejby will be included in the study. A total of 3 blood samples are obtained in the acute phase of STEMI: Prior to primary PCI (Blood sample 1), at 4 hours (Blood sample 2) and at 12 hours (Blood sample 3) after administration of loading dose aspirin and clopidogrel. When patients are in a stable phase 3 month later, a final blood sample is taken (Blood sample 4). The blood is analyzed 30 minutes after withdrawal of blood by the platelet aggregation test Multiplate® aggregometry (agonists: Collagen, arachidonic acid and adenosinediphosphate) and VerifyNow® arachidonic acid and P2Y12 aggregometry. Platelet count, volume and the immature platelet fraction (IPF) will be measured using Sysmex® flowcytometry.

Conditions

Acute Myocardial Infarction; Antiplatelet Therapy; ST-segment Elevation Myocardial Infarction (STEMI)

Keywords

STEMI; Acute myocardial infarction; Antiplatelet therapy; aspirin; clopidogrel; VerifyNow aggregometry; Multiplate aggregometry

Outcome Measures

Primary Outcomes (18)

• Difference between aggregation induced by agonist collagen (1 μg/ml) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 1: Obtained immediately before primary PCI in the catherization laboratory. The blood sample is obtained from the femoral artery catheter. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation induced by agonist collagen (1 μg/ml) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 2: 4 hours after administration of loading dose (LD) aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation induced by agonist collagen (1 μg/ml) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 3: 12 hours after administration of LD aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation induced by agonist arachidonic acid (1,0 mM) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 1: Obtained immediately before primary PCI in the catherization laboratory. The blood sample is obtained from the femoral artery catheter. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation induced by agonist arachidonic acid (1,0 mM) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 2: 4 hours after administration of loading dose (LD) aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation induced by agonist arachidonic acid (1,0 mM) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 3: 12 hours after administration of LD aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation induced by agonist adenosine diphosphate (6,4 µM) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 1: Obtained immediately before primary PCI in the catherization laboratory. The blood sample is obtained from the femoral artery catheter. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation induced by agonist adenosine diphosphate (6,4 µM) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 2: 4 hours after administration of loading dose (LD) aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation induced by agonist adenosine diphosphate (6,4 µM) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 3: 12 hours after administration of LD aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation induced by agonist adenosine diphosphate (20 µM) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 1: Obtained immediately before primary PCI in the catherization laboratory. The blood sample is obtained from the femoral artery catheter. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation induced by agonist adenosine diphosphate (20 µM) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 2: 4 hours after administration of loading dose (LD) aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation induced by agonist adenosine diphosphate (20 µM) measured by Multiplate® Aggregometry (Unit=AUC).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 3: 12 hours after administration of LD aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation measured by VerifyNow® Aggregometry using the ASPI-kit (Unit = ARU).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 1: Obtained immediately before primary PCI in the catherization laboratory. The blood sample is obtained from the femoral artery catheter. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation measured by VerifyNow® Aggregometry using the ASPI-kit (Unit = ARU).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 2: 4 hours after administration of loading dose (LD) aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation measured by VerifyNow® Aggregometry using the ASPI-kit (Unit = ARU).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 3: 12 hours after administration of LD aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation measured by VerifyNow® Aggregometry using the P2Y12-kit (Unit = PRU).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 1: Obtained immediately before primary PCI in the catherization laboratory. The blood sample is obtained from the femoral artery catheter. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation measured by VerifyNow® Aggregometry using the P2Y12-kit (Unit = PRU).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 2: 4 hours after administration of loading dose (LD) aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

• Difference between aggregation measured by VerifyNow® Aggregometry using the P2Y12-kit (Unit = PRU).

  Outcome is the difference between aggregation measurements. In this case between: Blood sample 3: 12 hours after administration of LD aspirin and clopidogrel. Blood sample 4: 2-3 months after primary PCI.

  Approximately 2-3 months

Secondary Outcomes (6)

• Difference in immature platelet fraction measured by Sysmex® flowcytometry.

  Approximately 2-3 months

• Difference in serum P-selectin

  Approximately 2-3 months

• Difference in serum trombopoietin

  Approximately 2-3 months

• Difference in serum thromboxane B2

  Approximately 2-3 months

• Difference in immature platelet fraction measured by Sysmex® flowcytometry.

  Approximately 2-3 months

Study Arms (1)

STEMI

Patients with STEMI according to ESC STEMI guidelines: Age above 18 years and able to give written, informed consent to participation in the project.

Eligibility Criteria

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

Study Population

Residents of the Central Denmark Region.

You may qualify if:

• Above 18 years of age
• Patients with ST-segment elevation myocardial infarction (STEMI) referred to primary PCI at University Hospital of Aarhus, Skejby.

You may not qualify if:

• Treatment with NSAID, ticlopidine and dipyramidole.
• Treatment with anticoagulants (Vitamin K antagonists)
• Patients diagnosed with platelet disease or haemophilia.
• Patients unable to give written, informed consent to participation in this project.

Sponsors & Collaborators

• University of Aarhus: lead
• AP Moeller Foundation: collaborator

Study Sites (1)

Aarhus University Hospital, Skejby

Aarhus N, Central Jutland, 8200, Denmark

Location

Related Publications (1)

• Funck-Jensen KL, Dalsgaard J, Grove EL, Hvas AM, Kristensen SD. Increased platelet aggregation and turnover in the acute phase of ST-elevation myocardial infarction. Platelets. 2013;24(7):528-37. doi: 10.3109/09537104.2012.738838. Epub 2012 Dec 5.

  PMID: 23216571 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample 1: * Whole blood (Platelet aggregation tests and flowcytometry) * Serum * S-Thromboxane B2 * S-Trombopoeitin * S-P-selectin * Plasma * DNA * RNA Blood sample 2: * Whole blood * Plasma Blood sample 3: * Whole blood * Plasma Blood sample 4: * Whole blood (Platelet aggregation tests and flowcytometry) * Serum * S-Thromboxane B2 * S-Trombopoeitin * S-P-selectin * Plasma * DNA * RNA

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Steen D Kristensen, MD, DMSc

  Aarhus University Hospital Skejby

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2010
• First Posted: June 16, 2010
• Study Start: October 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: August 1, 2010
• Last Updated: September 9, 2013

Record last verified: 2013-09

Locations

DK (1)