GRAVITAS: Gauging Responsiveness With A VerifyNow Assay-Impact On Thrombosis And Safety

Study Overview
=================
Brief Summary
-----------------
The objective of the GRAVITAS trial is to determine whether tailored anti-platelet therapy using the Accumetrics VerifyNow P2Y12 assay reduces major adverse cardiovascular events after drug-eluting stent implantation.

Official Title
-----------------
GRAVITAS: Gauging Responsiveness With A VerifyNow Assay-Impact On Thrombosis And Safety

Conditions
-----------------
Coronary Arteriosclerosis, Acute Coronary Syndrome

Intervention / Treatment
-----------------
* Drug: clopidogrel
* Drug: placebo
* Drug: clopidogrel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or females aged 18 years or older. 2. Patients undergoing coronary angiography and possible PCI with planned use of at least one drug-eluting stent (DES), and without planned use of glycoprotein IIb/IIIa inhibitors. One or more bare metal stents (BMS) may be implanted, and other lesions may be treated without stenting, as long as at least one DES is implanted. However, the procedure must be successful and uncomplicated for all lesions (DES + BMS + non stent). Indication for the procedure may be stable angina or ischemia, unstable angina, non-ST elevation MI (NSTEMI), or ST elevation MI (STEMI). Have the ability to understand the requirements of the study, including consent for use and disclosure of research-related health information. Have the ability to comply with study procedures and protocol, including required study visits. 6. A female patient is eligible to enter the study if she is (1) of child-bearing potential and not pregnant or nursing; (2) not of child-bearing potential (i.e., has had a hysterectomy, have both ovaries removed, has tubal ligation, or are post-menopausal, defined as 24 months without menses). Exclusion Criteria: Pre-PCI PCI within previous 30 days. Prior consent to participate in GRAVITAS and not randomized by IVRS. History of gastro-intestinal bleeding within 6 months. Major non-cardiac surgery within 6 weeks. Ischemic stroke within 6 weeks. Any history of hemorrhagic stroke or sub-arachnoid hemorrhage. Other bleeding diathesis, or considered by investigator to be at high-risk for bleeding on long-term clopidogrel therapy. Minor surgical procedures that require cessation of dual anti platelet therapy and result in significant bleeding are NOT eligible. Current or planned therapy with coumadin anticoagulation. Current or planned therapy with other thienopyridine class of ADP receptor inhibitors (e.g., prasugrel, ticlopidine), or the non-thienopyridine ticagrelor. Severe allergy to stainless steel, contrast dye, unfractionated heparin, low molecular weight heparin, or bivalirudin that cannot be adequately pre-medicated. Allergy to aspirin or clopidogrel. Current enrollment in an investigational drug or device study that has not reached the time period of the primary endpoint. Have received GPIIb/IIIa inhibitors eptifibatide or tirofiban within 24 hours before or during PCI or abciximab within 10 days before or during PCI. Thrombocytopenia (defined as platelet count < 100 K). Anemia (hematocrit < 30%). Polycythemia (hematocrit > 52%). Patients unwilling or unable to complete clinical follow-up for the duration of the study. Exclusion Criteria: Post-PCI PCI with placement of at least one DES is not performed. Planned staged PCI in the next 6 months post-procedure. Unsuccessful PCI (post-procedure diameter stenosis >30% with less than TIMI-3 flow in any treated vessel). Patients with in-hospital STEMI confirmed by ECG prior to randomization or those whom require a target vessel revascularization of the index lesion prior to randomization. Patients with acute stent thrombosis before Accumetrics VerifyNow tests. Administration of any GPIIb/IIIa during PCI procedure or prior to initial hospital discharge. Failure to meet clopidogrel requirements Major complication during or after PCI

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Tailored clopidogrel regimen - an additional clopidogrel 600-mg loading dose (eight 75-mg tablets taken orally; daily 150 mg clopidogrel dose plus additional 450 mg clopidogrel) on the day of randomization and then 150-mg clopidogrel every day thereafter for 6 months. | Drug: clopidogrel<br>* oral, 75 mg daily for 6 months starting on day of randomization<br>Drug: clopidogrel<br>* oral, 450 mg loading dose on day of randomization; 75 mg daily for 6 months starting on day of randomization<br>|
| Placebo Comparator: B<br>Standard clopidogrel regimen - a placebo loading dose (six placebo tablets taken orally plus daily dose of one placebo tablet plus 75 mg clopidogrel) on the day of randomization followed by one placebo tablet plus 75 mg clopidogrel every day thereafter for 6 months. | Drug: clopidogrel<br>* oral, 75 mg daily for 6 months starting on day of randomization<br>Drug: placebo<br>* oral, 6 pill loading dose on day of randomization; one pill daily for 6 months starting on day of randomization<br>|
| Placebo Comparator: C<br>Responders: A random sample of clopidogrel responders treated with a placebo loading dose (six placebo tablets taken orally plus daily dose of one placebo tablet plus 75 mg clopidogrel) on the day of randomization followed by one placebo tablet plus 75 mg clopidogrel every day thereafter for 6 months. | Drug: clopidogrel<br>* oral, 75 mg daily for 6 months starting on day of randomization<br>Drug: placebo<br>* oral, 6 pill loading dose on day of randomization; one pill daily for 6 months starting on day of randomization<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first occurrence of post-randomization CV death, non-fatal MI, or ARC definite/probable stent thrombosis in non-responders randomized to standard vs. tailored dosage |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first occurrence of post-randomization CV death, non-fatal MI, or ARC definite/probable stent thrombosis in non-responders randomized to standard dosage vs. responders |  | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Platelets, Platelet Function Tests, Clopidogrel, Drug Eluting Stents, Acute Coronary Syndrome, Myocardial Ischemia, Stent Thrombosis, Heart Diseases, Coronary Disease, Arterial Occlusive Disease