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

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.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome; Coronary Arteriosclerosis
• Intervention / Treatment: Drug: clopidogrel; Drug: clopidogrel; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 2800
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • Royal Alexandra Hospital
  • Ontario
    • Hamilton, Ontario, Canada
      • McMaster University
    • Newmarket, Ontario, Canada
      • York PCI Group
    • Ottawa, Ontario, Canada
      • University of Ottawa Heart Institute
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montréal, Quebec, Canada
      • Montreal Heart Institute
    • Montréal, Quebec, Canada
      • Hopital du Sacre-Coeur de Montreal
    • Montréal, Quebec, Canada
      • Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu
    • Montréal, Quebec, Canada
      • Royal Victoria Hospital
    • Québec, Quebec, Canada
      • Hôpital Laval
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Health Care - Osborn Campus
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Health Care - Shea Campus
  • California
    • La Jolla, California, United States, 92037
      • Scripps Green Hospital
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • Sacramento, California, United States, 95825
      • Sacramento Heart and Vascular Research Center
    • San Diego, California, United States, 92103
      • UCSD Medical Center
    • San Diego, California, United States, 92120
      • Alvarado Hospital
    • San Francisco, California, United States, 94110
      • San Francisco General Hospital
    • San Francisco, California, United States, 94143
      • UCSF Moffitt-Long Hospital
    • Santa Barbara, California, United States, 93105
      • Santa Barbara Cottage Hospital
    • Torrance, California, United States, 90503
      • Torrance Memorial Medical Center
  • Connecticut
    • Bridgeport, Connecticut, United States, 06610
      • Bridgeport Hospital
    • Danbury, Connecticut, United States, 06810
      • Danbury Hospital
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Clearwater, Florida, United States, 33756
      • Clearwater Cardiovascular and Interventional Consultants
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Science Center
    • Ormond Beach, Florida, United States, 32174
      • Cardiology Research Associates
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • St. Joseph's Research Institute
    • Rome, Georgia, United States, 30165
      • Redmond Regional Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois Medical Center
    • Chicago, Illinois, United States, 60612
      • Jesse Brown VA Medical Center
    • Moline, Illinois, United States, 61265
      • Trinity Medical Center
    • Springfield, Illinois, United States, 62701
      • Prairie Education & Research Cooperative
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • St. Vincent Heart Center of Indiana/The Care Group LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70232
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Union Memorial Hospital
    • Takoma Park, Maryland, United States, 20912
      • Washington Adventist Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center
    • Burlington, Massachusetts, United States, 01803
      • The Lahey Clinic
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Michigan
    • Petoskey, Michigan, United States, 49770
      • Cardiac and Vascular Research Center of Northern Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
    • Ypsilanti, Michigan, United States, 48197
      • St. Joseph's Mercy Hospital
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • St. Mary's Duluth Clinic Health System
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's / Mid America Heart Institute
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10021
      • Lenox Hill Hospital
    • New York, New York, United States, 10021
      • NY Presbyterian / Weill Cornell Medical Center
    • Poughkeepsie, New York, United States, 12601
      • Hudson Valley Heart Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Durham VA Medical Center
    • High Point, North Carolina, United States, 27262
      • Carolina Cardiology Associates
    • Raleigh, North Carolina, United States, 27610
      • Wake Heart Research
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Clinical Trial Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
    • Elyria, Ohio, United States, 44035
      • North Ohio Research, Ltd.
    • Fairview Park, Ohio, United States, 44126
      • Cleveland Cardiovascular Research Foundation
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Science Center
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Cardiovascular Associates
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Clinic - Cardiology
    • Erie, Pennsylvania, United States, 16502
      • St. Vincent Health Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Clinical Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Centennial Medical Center
  • Texas
    • Austin, Texas, United States, 78704
      • South Austin Hospital
    • Austin, Texas, United States, 78756
      • Austin Heart P.A.
    • Dallas, Texas, United States, 75226
      • Baylor Heart and Vascular Hospital
    • Fort Worth, Texas, United States, 76104
      • Plaza Medical Center of Fort Worth
    • Houston, Texas, United States, 77030
      • The Methodist Hospital
    • San Antonio, Texas, United States, 78229
      • University Hospital San Antonio (UTHSCSA)
    • Tomball, Texas, United States, 77375
      • Tomball Regional Hospital

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:

• 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

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: clopidogrel; oral, 75 mg 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
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.	Drug: clopidogrel; oral, 75 mg 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; Drug: placebo; oral, 6 pill loading dose on day of randomization; one pill daily for 6 months starting on day of randomization
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.	Drug: clopidogrel; oral, 75 mg 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; Drug: placebo; oral, 6 pill loading dose on day of randomization; one pill daily for 6 months starting on day of randomization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Accumetrics, Inc.
• Investigators: Principal Investigator: Matthew J Price, M.D., Scripps Advanced Clnical Trials

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): October 1, 2010
• Study Completion (ACTUAL): October 1, 2010

Study Registration Dates

• First Submitted: March 24, 2008
• First Submitted That Met QC Criteria: March 26, 2008
• First Posted (ESTIMATE): March 28, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): June 16, 2011
• Last Update Submitted That Met QC Criteria: June 15, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: Acute Coronary Syndrome; Platelets; Platelet Function Tests; Clopidogrel; Stent Thrombosis; Heart Diseases; Myocardial Ischemia; Coronary Disease; Drug Eluting Stents; Arterial Occlusive Disease
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Embolism and Thrombosis; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Thrombosis; Arteriosclerosis; 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: P95082