Role of Tirofiban and the Paclitaxel Eluting Stent in Postfibrinolysis Angioplasty (GRACIA3)

A Randomised Trial to Evaluate the Role of Paclitaxel Eluting Stent and Tirofiban to Improve the Results of Facilitated PCI in the Treatment of Acute ST- Segment Elevation Myocardial Infarction

The conceptual hypothesis of this study is that, in patients with acute myocardial infarction and ST-segment elevation, the strategy of performing coronary angioplasty of the culprit artery with paclitaxel eluting stent significantly reduces the rate of restenosis in comparison with bare stents.

The conceptual hypothesis of this study is that, in patients with acute myocardial infarction and ST-segment elevation, the strategy of performing coronary stent-angioplasty of the culprit artery under the protection of tirofiban 120 minutes after fibrinolytic significantly improves epicardial and myocardial infusion in comparison with the strategy of performing immediate intravenous thrombolysis (tenecteplase plus enoxaparine) followed by coronary angiography and adequate revascularization.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction
• Intervention / Treatment: Procedure: Postfibrinolysis percutaneous coronary intervention; Procedure: Postfibrinolysis percutaneous coronary intervention; Procedure: Postfibrinolysis percutaneous coronary intervention; Procedure: Postfibrinolysis percutaneous coronary intervention

Detailed Description

The primary objectives of this study are: first to determine the efficacy of paclitaxel eluting stent compared to conventional bare stent in terms of restenosis, and second to determine the effect of tirofiban administered prior to percutaneous coronary intervention (PCI) but 120 minutes after thrombolytic on the epicardial and myocardial flow after mechanical revascularization in patients with STEMI.

Methods: This is a phased 4, 2x2 randomised, open, multicenter, clinical study. Patients will be randomised 1:1:1:1 to four groups: a) paclitaxel eluting stent with tirofiban, b) paclitaxel eluting stent without tirofiban, c) bare stent with tirofiban and d) bare stent without tirofiban. A total of approximately 436 patients, with <12 hours STEMI will be enrolled. All patients will be initially treated with tenecteplase (TNK) and enoxaparin. Tirofiban will start 120 minutes after tenecteplase administration in those patients randomised to tirofiban. Cardiac catheterization will be performed within the first 3-12 hours after the study inclusion and stenting on the culprit artery, with the randomised paclitaxel or bare stent, will be performed.

The efficacy of these strategies will be measured in terms of: 1) binary restenosis, defined as >50% diameter stenosis and segment analysis including the stented segment as well as their margins, 5 mm proximal and distal to the stent at 9-12 months follow-up and, 2) the assessment of the epicardial and myocardial perfusion (%TIMI 3, CTFC, CFR-CTFC, TMP y DSA-TMP and the analysis of the normalization of the ST segment at 90 minutes, 3, 6, 12 and 24 hours after thrombolysis).

• Study Type: Interventional
• Enrollment (Actual): 436
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Valladolid, Spain, 47005
    • Instituto de Ciencias del Corazón (ICICOR). Hospital Clínico Universitario de Valladolid

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:

Patients with ST-segment elevation acute myocardial infarction with all of the following criteria will be eligible for enrollment:

1. Age >18 years.
2. Chest discomfort >30 minutes with no response to nitroglycerin.
3. Time from the onset of symptoms to randomization < 12 hours.
4. ST segment elevation > 1 mm in two or more limb leads or 2 mm in two or more contiguous precordial leads or non-diagnostic ECG (left bundle branch block or pacemaker rhythm) with classic symptoms.
5. Killip class > 3.
6. Written informed consent will be obtained.

Exclusion Criteria:

Patients presenting with any of the following will not be included in the study.

1. Cardiogenic shock defined as a systolic blood pressure <90 mm Hg without response to fluid administration or <100 mmHg in patients with supportive treatment and no bradycardia.
2. Suspected mechanical complications of acute myocardial infarction.
3. Previous CABG.
4. Non-cardiac disease that is likely to jeopardize the planned termination of the study.
5. Woman of childbearing potential unless a negative pregnant test.
6. Active bleeding and recent (within 2 weeks) surgery that contraindicate the use of heparin, tirofiban, or platelet aggregation inhibitors.

7. Contraindications for thrombolytic use.

   • previous hemorrhagic stroke at any time
   • history of prior non-hemorrhagic cerebrovascular accident within 12 months
   • intracerebral neoplasia
   • active internal bleeding
   • suspected aortic dissection
   • Uncontrolled hypertension >180/110 in several measurements
   • any other known intracerebral pathology not covered in contraindications
   • Current use of anticoagulants or heparin use within 8 hours
   • known bleeding diathesis
   • recent trauma (< 4 weeks), including head trauma or traumatic or prolonged (>10 minutes) CPR or recent major surgery or biopsy (<8 weeks)
   • noncompressible vascular punctures
   • recent (< 4 weeks) internal bleeding
   • pregnancy
   • active peptic ulcer
8. History of hypersensitivity to aspirin, ticlopidine, clopidogrel, heparin, tirofiban and stainless steel.
9. Known renal failure, creatinine >2,5 mg/dL.
10. Known impaired hepatic function that contraindicates the use of clopidogrel.
11. Known thrombocytopenia (100.000).
12. Participation in other trial.
13. Known multivessel disease identified as no suitable for revascularization.
14. Known peripheral vascular disease that difficult cardiac catheterization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: bare-metal stent without tirofiban; implantation of a bare-metal stent with no tirofiban infusion after fibrinolysis	Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a bare-metal stent with no infusion of tirofiban 120 minutes after fibrinolysis; Other Names: Express stents (Boston Scientific, Natick, Massachusetts); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a bare-metal stent with infusion of tirofiban 120 minutes after fibrinolysis; Other Names: Express stents (Boston Scientific, Natick, Massachusetts); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a paclitaxel eluting-stent with no infusion of tirofiban 120 minutes after fibrinolysis; Other Names: TAXUS stents (Boston Scientific); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a paclitaxel eluting-stent with infusion of tirofiban 120 minutes after fibrinolysis; Other Names: TAXUS stents (Boston Scientific)
Active Comparator: bare-metal stent with tirofiban; implantation of a bare-metal stent with tirofiban infusion after fibrinolysis	Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a bare-metal stent with no infusion of tirofiban 120 minutes after fibrinolysis; Other Names: Express stents (Boston Scientific, Natick, Massachusetts); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a bare-metal stent with infusion of tirofiban 120 minutes after fibrinolysis; Other Names: Express stents (Boston Scientific, Natick, Massachusetts); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a paclitaxel eluting-stent with no infusion of tirofiban 120 minutes after fibrinolysis; Other Names: TAXUS stents (Boston Scientific); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a paclitaxel eluting-stent with infusion of tirofiban 120 minutes after fibrinolysis; Other Names: TAXUS stents (Boston Scientific)
Active Comparator: paclitaxel-eluting stent without tirofiban; implantation of a paclitaxel eluting-stent with no tirofiban after fibrinolysis	Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a bare-metal stent with no infusion of tirofiban 120 minutes after fibrinolysis; Other Names: Express stents (Boston Scientific, Natick, Massachusetts); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a bare-metal stent with infusion of tirofiban 120 minutes after fibrinolysis; Other Names: Express stents (Boston Scientific, Natick, Massachusetts); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a paclitaxel eluting-stent with no infusion of tirofiban 120 minutes after fibrinolysis; Other Names: TAXUS stents (Boston Scientific); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a paclitaxel eluting-stent with infusion of tirofiban 120 minutes after fibrinolysis; Other Names: TAXUS stents (Boston Scientific)
Active Comparator: paclitaxel-eluting stent with tirofiban; implantation of a paclitaxel eluting-stent with tirofiban infusion after fibrinolysis	Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a bare-metal stent with no infusion of tirofiban 120 minutes after fibrinolysis; Other Names: Express stents (Boston Scientific, Natick, Massachusetts); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a bare-metal stent with infusion of tirofiban 120 minutes after fibrinolysis; Other Names: Express stents (Boston Scientific, Natick, Massachusetts); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a paclitaxel eluting-stent with no infusion of tirofiban 120 minutes after fibrinolysis; Other Names: TAXUS stents (Boston Scientific); Procedure: Postfibrinolysis percutaneous coronary intervention; implantation of a paclitaxel eluting-stent with infusion of tirofiban 120 minutes after fibrinolysis; Other Names: TAXUS stents (Boston Scientific)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
to determine the efficacy of paclitaxel eluting stent compared to conventional bare stent in terms of restenosis	12 months
to determine the effect of tirofiban administered prior to PCI but 120 minutes after thrombolytic on the epicardial and myocardial flow after mechanical revascularization in patients with STEMI	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
to determine the safety of paclitaxel eluting stent in terms of rate of complications, and particularly acute and subacute total occlusion.	12 months
to determine the interaction of paclitaxel eluting stent and the complicated myocardial infarction lesion in terms of reduction of intimal proliferation as evaluated by quantitative coronary angiography	12 months
to determine the efficacy of paclitaxel eluting stent in different subgroups of patients: diabetics, small vessel (<2.5 mm), long lesion (>15 mm), gender, and tirofiban use.	12 months
to determine the efficacy and safety of full dose fibrinolytic therapy plus delayed tirofiban compared to fibrinolytic therapy alone in different subgroups: diabetics and the elderly	30 days
to determine the efficacy of use of tirofiban in relation to time to fibrinolytic therapy and time to mechanical revascularization.	24 hours
to determine possible interactions between the paclitaxel eluting stent and tirofiban in terms of restenosis or acute and subacute total occlusion following coronary stenting.	12 months

Collaborators and Investigators

• Sponsor: GRACIA Group
• Collaborators: Spanish Ministry of Health.; Spanish Ministry of Science and Innovation
• Investigators: Study Chair: Francisco Fernandez-Aviles, MD, PhD, ICICOR, Hospital Clínico Universitario Valladolid, Spain

Publications and helpful links

General Publications

• Sanchez PL, Gimeno F, Ancillo P, Sanz JJ, Alonso-Briales JH, Bosa F, Santos I, Sanchis J, Bethencourt A, Lopez-Messa J, de Prado AP, Alonso JJ, San Roman JA, Fernandez-Aviles F. Role of the paclitaxel-eluting stent and tirofiban in patients with ST-elevation myocardial infarction undergoing postfibrinolysis angioplasty: the GRACIA-3 randomized clinical trial. Circ Cardiovasc Interv. 2010 Aug;3(4):297-307. doi: 10.1161/CIRCINTERVENTIONS.109.920868.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: March 21, 2006
• First Submitted That Met QC Criteria: March 21, 2006
• First Posted (Estimate): March 23, 2006

Study Record Updates

• Last Update Posted (Estimate): September 28, 2009
• Last Update Submitted That Met QC Criteria: September 25, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: paclitaxel; tirofiban; Thrombolysis; ST elevation acute myocardial infarction; Early routine percutaneous coronary intervention
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: GRACIA 3