Tailoring Of Platelet Inhibition to Avoid Stent Thrombosis (TOPAS-1)

TOPAS-1, A Pharmacodynamic Phase II Study of Clopidogrel P2Y12 Platelet Inhibition

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Heart Diseases; Coronary Artery Disease; Acute Coronary Syndrome; Stent Thrombosis
• Intervention / Treatment: Drug: Clopidogrel

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.

• Study Type: Interventional
• Enrollment (Anticipated): 450
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden, 75185
    • Uppsala Clinical Research Center

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Patients with previously experienced stent thrombosis while on dual antiplatelet treatment within 6 months after coronary stenting for coronary artery disease	Drug: Clopidogrel; Patients not already on clopidogrel treatment a loading dose of clopidogrel 600 mg followed by a maintenance dose of 75 mg once daily will be administered.; Other Names: Plavix
Active Comparator: 2; Patients with previously experienced myocardial infarction while on dual antiplatelet treatment within 6 months after coronary stenting for coronary artery disease	Drug: Clopidogrel; Patients not already on clopidogrel treatment a loading dose of clopidogrel 600 mg followed by a maintenance dose of 75 mg once daily will be administered.; Other Names: Plavix
Active Comparator: 3; Patients without previously experienced myocardial infarction or stent thrombosis 6 within months after coronary stenting for coronary artery disease(matched controls for group 1 and 2)	Drug: Clopidogrel; Patients not already on clopidogrel treatment a loading dose of clopidogrel 600 mg followed by a maintenance dose of 75 mg once daily will be administered.; Other Names: Plavix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
VerifyNow P2Y12 (PRU)	Within 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
VASP (PRI, %)	Within 6 months

Collaborators and Investigators

• Sponsor: Uppsala University
• Investigators: Principal Investigator: Lars Wallentin, MD, PhD, Uppsala University, Uppsala Clinical Research Center

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: May 29, 2009
• First Submitted That Met QC Criteria: June 4, 2009
• First Posted (Estimate): June 5, 2009

Study Record Updates

• Last Update Posted (Estimate): April 13, 2010
• Last Update Submitted That Met QC Criteria: April 12, 2010
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Aspirin; Pathologic Processes; Cardiovascular Diseases; Syndrome; Platelet Aggregation Inhibitors; Clopidogrel; Pharmacologic Actions; Disease; Therapeutic Uses; Hematologic Agents
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Embolism and Thrombosis; Coronary Disease; Myocardial Infarction; Infarction; Heart Diseases; Coronary Artery Disease; Thrombosis; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: U-08-002