Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel

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Complete Title of Study
Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel

Study Acronym (The trial's abbreviation if there is one)
3T/2R

Principal Investigator, Co-investigators, and Collaborating Institutions
Principal investigator: 	Marco Valgimigli, MD, PhD

Institution: Universitaria di Ferrara, Ferrara, Fe, Italy

Overview of Trial
The goal of the study was to evaluate whether adding tirofiban, administered at high bolus dose on top of aspirin and clopidogrel will lead to a lower rate of periprocedural myocardial infarction after percutaneous coronary intervention in elective patients presenting with aspirin and/or clopidogrel resistance.

Disease State(s) Studied (e.g. acute MI, breast cancer, etc.)
Coronary artery disease

Study Phase (e.g. Phase I,II,III,IV) Study Phases are defined here
Phase IV

Study Design (e.g. multicenter, randomized, double blind, placebo controlled)
Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Treatment, Parallel Assignment, Efficacy Study

Study Arms and How They Were Treated (Intervention) (Explanation here)
263 patients were randomized to either an experimental arm (Aspirin, clopidogrel, Unfractioned heparin or bivalirudin plus tirofiban infusion given at high bolus dose plus standard 14-24 hour infusion) or a placebo arm (Saline infusion administered for 14-24 hours).

Primary Pre-Specified Endpoint
Troponin I or T elevation ratio at least three times the upper limit of normal

Secondary Endpoints

 * The incidence of myocardial infarction defined as elevation of CK-MB >1, ≥3 or ≥5 times the ULN in one or more blood samples (time frame: 30 days)
 * Elevation of troponin levels above upper limit of normal in ratios different from the primary endpoint (within 30 days)
 * Bleeding rates (time frame: 30 days)
 * Stent thrombosis with the first year of follow-up
 * Rate of major adverse cardiovascular events at 30 days and 1 year

Inclusion Criteria
Patients older than 18 years scheduled for coronary angiography and/or PCI with stable or unstable troponin and CK-MB negative coronary artery disease showing aspirin and or clopidogrel resistance (ACR.)

Exclusion Criteria

 * Inability to provide informed consent
 * Life expectancy of < 1 year
 * Evolving or ongoing myocardial infarction (MI) (Persistence of or developing Q wave or ST segment elevation at ECG with or without typical chest pain or typical rapid rise and fall CK-MB or new LBBB) or patients in whom the treating physician intends to use a Gp IIB/IIIa inhibitors
 * Administration of any GP IIb/IIIa receptor antagonist, anticoagulation, or lytic therapy in the previous 30 days
 * Serum creatinine > 2.5 mg/dl (221 micromol/L)
 * Ongoing bleeding or bleeding diathesis or contraindication for anticoagulation or increase bleeding risk or history of bleeding in the last 1 year
 * Previous stroke or TIA or any intracranial pathology in the last six months
 * Major surgery or trauma within the previous six weeks
 * Platelet count < 100.000 per cubic mm or HCT ,33% or Hb < 11 gm/dL
 * Subjects who received low-molecular-weight heparin within the 24 hours prior to randomization
 * Subjects with an allergy or intolerance to aspirin, heparin, clopidogrel, or tirofiban
 * Patients with severe hypertension (SBP > 180 mm Hg or DBP > 110 mm Hg) or in cardiogenic shock (SBP 80 mm Hg or below for > 30 minutes) or requiring IABP

Outcome: Primary endpoint (Report both relative risk reduction and absolute risk reduction as well as number needed to treat if available)
None reported

Outcome: Secondary endpoint (Report both relative risk reduction and absolute risk reduction as well as number needed to treat if available)
None reported

Outcome: Exploratory endpoints (Report both relative risk reduction and absolute risk reduction as well as number needed to treat if available)
None reported

Outcome: Safety endpoints (Report both relative risk and absolute risk as well as number needed to harm if available)
None reported

Conclusions of the Investigators (Quote the investigators conclusions here)
None reported

Commentary, Discussion and Limitations of the Trial (Anyone can add comments)
None reported

Slides
None reported

Video Commentary
None reported

References (How to insert a reference)
Chen WH, Lee PY, Ng W, Tse HF, Lau CP. Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment. J Am Coll Cardiol. 2004 Mar 17;43(6):1122-6. PMID 15028378

Valgimigli M, Percoco G, Barbieri D, Ferrari F, Guardigli G, Parrinello G, Soukhomovskaia O, Ferrari R. The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: the ADVANCE Trial. J Am Coll Cardiol. 2004 Jul 7;44(1):14-9. PMID 15234398

External sites for further information (How to insert links)
[http://www.ncbi.nlm.nih.gov/pubmed/15028378?dopt=Abstract Chen WH, Lee PY, Ng W, Tse HF, Lau CP. Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment. J Am Coll Cardiol. 2004 Mar 17;43(6):1122-6.]

[http://www.ncbi.nlm.nih.gov/pubmed/15234398?dopt=Abstract Valgimigli M, Percoco G, Barbieri D, Ferrari F, Guardigli G, Parrinello G, Soukhomovskaia O, Ferrari R. The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: the ADVANCE Trial. J Am Coll Cardiol. 2004 Jul 7;44(1):14-9.]

Detailed information about the trial
This study investigated the effect of treatment with a high bolus dosage of Tirofiban (in addition to Aspirin, Heparin and 300mg or 600mg clopidogrel) on the rate of periprocedural myocardial infarction compared to Aspirin, Heparin (or bivalirudin) and 300mg or 600mg clopidogrel alone in patients resistant to aspirin and/or to clopidogrel. This is a randomized, double blind, placebo controlled (with bailout tirofiban as rescue) multicenter study. Enrollment will last between 12 and 36 months depending on the final number of participating centres. The minimum follow-up will be 30 days after the index procedure.

Ages
18 years and older

Gender (Indicate whether men, women or both were enrolled)
Both men and women were eligible for the study

Accepts Healthy Volunteers (Answer yes or no)
No

Enrollment Period (Study start and end date)
Study start date: May 2006

Estimated study completion date: May 2011

Primary completion date: July 2008 (Final data collection date for primary outcome measure)

Recruitment Status (explanation)
Study is ongoing but not recruiting participants

Enrollment (Total number of patients enrolled)
263

Study Sponsor (e.g. Investigator initiated or company name)
Universitaria di Ferrara

Source of Data (Where is this data on this page coming from: publication, principal investigator, or co-investigator)
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