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

• ClinicalTrials.gov Identifier: NCT00645918
• Recruitment Status: Completed
• First Posted: March 28, 2008
• Last Update Posted: June 16, 2011
• Sponsor: Accumetrics, Inc.
• Information provided by: Accumetrics, Inc.

Tracking Information

• First Submitted Date: March 24, 2008
• First Posted Date: March 28, 2008
• Last Update Posted Date: June 16, 2011
• Study Start Date: June 2008
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 26, 2008): 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 [ Time Frame: 6 months ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: March 26, 2008): 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 [ Time Frame: 6 months ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: GRAVITAS: Gauging Responsiveness With A VerifyNow Assay-Impact On Thrombosis And Safety
• Official Title: GRAVITAS: Gauging Responsiveness With A VerifyNow Assay-Impact On Thrombosis And Safety
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator)

Condition

• Coronary Arteriosclerosis
• Acute Coronary Syndrome

Intervention

• Drug: clopidogrel
  oral, 75 mg daily for 6 months starting on day of randomization
• Drug: placebo
  oral, 6 pill loading dose on day of randomization; one pill daily for 6 months starting on day of randomization
• Drug: clopidogrel
  oral, 450 mg loading dose on day of randomization; 75 mg daily for 6 months starting on day of randomization

Study Arms

• Active Comparator: A
  "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.
  Interventions:

  • Drug: clopidogrel
  • Drug: clopidogrel
• Placebo Comparator: B
  "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.
  Interventions:

  • Drug: clopidogrel
  • Drug: placebo
• Placebo Comparator: C
  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.
  Interventions:

  • Drug: clopidogrel
  • Drug: placebo

Publications *

• Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB, Tanguay JF, Cannon CP, Topol EJ. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Circulation. 2011 Sep 6;124(10):1132-7. doi: 10.1161/CIRCULATIONAHA.111.029165. Epub 2011 Aug 29.
• Price MJ, Berger PB, Teirstein PS, Tanguay JF, Angiolillo DJ, Spriggs D, Puri S, Robbins M, Garratt KN, Bertrand OF, Stillabower ME, Aragon JR, Kandzari DE, Stinis CT, Lee MS, Manoukian SV, Cannon CP, Schork NJ, Topol EJ; GRAVITAS Investigators. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011 Mar 16;305(11):1097-105. doi: 10.1001/jama.2011.290. Erratum In: JAMA. 2011 Jun 1;305(21);2174. Stillablower, Michael E [corrected to Stillabower, Michael E].
• Price MJ, Berger PB, Angiolillo DJ, Teirstein PS, Tanguay JF, Kandzari DE, Cannon CP, Topol EJ. Evaluation of individualized clopidogrel therapy after drug-eluting stent implantation in patients with high residual platelet reactivity: design and rationale of the GRAVITAS trial. Am Heart J. 2009 May;157(5):818-24, 824.e1. doi: 10.1016/j.ahj.2009.02.012.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 20, 2010): 2800
• Original Estimated Enrollment (submitted: March 26, 2008): 2783
• Actual Study Completion Date: October 2010
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00645918
• Other Study ID Numbers: P95082
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Matthew J. Price, M.D., Scripps Advanced Clinical Trials
• Original Responsible Party: Same as current
• Current Study Sponsor: Accumetrics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Matthew J Price, M.D.; Scripps Advanced Clnical Trials

• PRS Account: Accumetrics, Inc.
• Verification Date: June 2011