Clinical trial NCT00914368: Tailoring Of Platelet Inhibition to Avoid Stent Thrombosis
Official title: TOPAS-1, A Pharmacodynamic Phase II Study of Clopidogrel P2Y12 Platelet Inhibition
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Disease
Myocardial Infarction
Stent Thrombosis
Heart Diseases
Acute Coronary Syndrome
Keywords: Platelet Aggregation Inhibitors
Aspirin
Clopidogrel
Pathologic Processes
Disease
Therapeutic Uses
Syndrome
Hematologic Agents
Cardiovascular Diseases
Pharmacologic Actions
Lead sponsor: Uppsala University
Sponsor class: OTHER
First posted: 2009-06-05
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: The primary objective of this study is to establish a cut off level of platelet inhibition that separates patients with or without previous stent occlusion with acute clinical onset while on aspirin and clopidogrel treatment within 6 months after coronary stenting for coronary artery disease.

Detailed description: To establish cut off levels of platelet inhibition using ADP-induced P2Y12-receptor mediated platelet aggregation using Accumetrics VerifyNow P2Y12 assay (PRU) and Vasodilator-stimulated phosphoprotein (VASP, PRI %)for patients with experienced stent occlusion with acute clinical onset and/or myocardial infarction within 6 months after coronary stenting for coronary artery disease.

Eligibility criteria: Inclusion Criteria:

* Provide signed written informed consent.
* Male or female patients above 18 years old.
* Previous PCI and coronary stenting for coronary artery disease
* Previous (after coronary stenting) or current dual antiplatelet treatment (aspirin 75 mg once daily (o.d) and clopidogrel 75 mg o.d). All patients need to be on treatment with aspirin 75 mg once daily at least seven days prior to enrollment.
* Experienced one of the following alternatives:

  * Stent thrombosis within 6 months of PCI while on dual antiplatelet treatment; OR
  * Experienced MI within 6 month after coronary stenting while on dual antiplatelet treatment; OR
  * No experience of stent thrombosis or MI for at least 6 months and until visit 1 (matched control)

Exclusion Criteria:

General exclusion criteria:

1. Women who are known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding.
2. Any condition or laboratory findings which in the opinion of the Investigator makes the patient unsuitable for inclusion
3. Enrolled in either another investigational drug study or in another investigational study of an approved drug within 30 days prior to Visit 1 of the current study.
4. Known allergies or intolerance to aspirin and/or thienopyridines (clopidogrel or ticlopidine).
5. Significant active neuropsychiatric disease, alcohol abuse or drug abuse, in the investigator's opinion.
6. UCR or Accumetrics employees or investigator site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.

   Cardiovascular Exclusion Criteria:
7. Subjects with unstable coronary artery disease, defined as new, increased, or rest angina at screening.
8. Subjects with significant hypertension (systolic blood pressure \> 180 mm Hg or diastolic blood pressure \>110 mmHg) at the time of screening.

   Bleeding Risk Exclusion Criteria:
9. Any known contraindication to treatment with an anticoagulant or antiplatelet agent.
10. Prior history or presence of significant bleeding disorders (for example,hematemesis, melena, severe or recurrent epistaxis, hemoptysis, hematuria, or intraocular bleeding)
11. Prior history or clinical suspicion of cerebral vascular malformations
12. Prior history of abnormal bleeding tendency (i.e. prolonged bleeding on dental extraction, tonsillectomy, or previous surgical procedure).
13. Personal or family history of coagulation or bleeding disorders.
14. Thrombocytopenia (platelet count \< 100,000/mm3) or thrombocytosis (platelet count \> 500,000/mm3).
15. History of major surgery, severe trauma, organ biopsy within 3 months prior to enrollment.
16. Any planned surgical procedure within 20 days following inclusion.
17. The use (or planned use) of other antiplatelet agents (besides aspirin and clopidogrel), anticoagulant or fibrinolytic agents.

Primary outcomes:
measure: VerifyNow P2Y12 (PRU)
timeFrame: Within 6 months
Secondary outcomes:
measure: VASP (PRI, %)
timeFrame: Within 6 months
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala Clinical Research Center
Study officials:
affiliation: Uppsala University, Uppsala Clinical Research Center
name: Lars Wallentin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: