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

Primary Purpose

Myocardial Infarction

Status
Completed
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Postfibrinolysis percutaneous coronary intervention
Postfibrinolysis percutaneous coronary intervention
Postfibrinolysis percutaneous coronary intervention
Postfibrinolysis percutaneous coronary intervention
Sponsored by
GRACIA Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myocardial Infarction focused on measuring ST elevation acute myocardial infarction, Thrombolysis, Early routine percutaneous coronary intervention, tirofiban, paclitaxel

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients with ST-segment elevation acute myocardial infarction with all of the following criteria will be eligible for enrollment: Age >18 years. Chest discomfort >30 minutes with no response to nitroglycerin. Time from the onset of symptoms to randomization < 12 hours. 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. Killip class > 3. Written informed consent will be obtained. Exclusion Criteria: Patients presenting with any of the following will not be included in the study. 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. Suspected mechanical complications of acute myocardial infarction. Previous CABG. Non-cardiac disease that is likely to jeopardize the planned termination of the study. Woman of childbearing potential unless a negative pregnant test. Active bleeding and recent (within 2 weeks) surgery that contraindicate the use of heparin, tirofiban, or platelet aggregation inhibitors. 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 History of hypersensitivity to aspirin, ticlopidine, clopidogrel, heparin, tirofiban and stainless steel. Known renal failure, creatinine >2,5 mg/dL. Known impaired hepatic function that contraindicates the use of clopidogrel. Known thrombocytopenia (100.000). Participation in other trial. Known multivessel disease identified as no suitable for revascularization. Known peripheral vascular disease that difficult cardiac catheterization.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

bare-metal stent without tirofiban

bare-metal stent with tirofiban

paclitaxel-eluting stent without tirofiban

paclitaxel-eluting stent with tirofiban

Arm Description

implantation of a bare-metal stent with no tirofiban infusion after fibrinolysis

implantation of a bare-metal stent with tirofiban infusion after fibrinolysis

implantation of a paclitaxel eluting-stent with no tirofiban after fibrinolysis

implantation of a paclitaxel eluting-stent with tirofiban infusion after fibrinolysis

Outcomes

Primary Outcome Measures

to determine the efficacy of paclitaxel eluting stent compared to conventional bare stent in terms of restenosis
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

Secondary Outcome Measures

to determine the safety of paclitaxel eluting stent in terms of rate of complications, and particularly acute and subacute total occlusion.
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
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.
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
to determine the efficacy of use of tirofiban in relation to time to fibrinolytic therapy and time to mechanical revascularization.
to determine possible interactions between the paclitaxel eluting stent and tirofiban in terms of restenosis or acute and subacute total occlusion following coronary stenting.

Full Information

First Posted
March 21, 2006
Last Updated
September 25, 2009
Sponsor
GRACIA Group
Collaborators
Spanish Ministry of Health., Spanish Ministry of Science and Innovation
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1. Study Identification

Unique Protocol Identification Number
NCT00306228
Brief Title
Role of Tirofiban and the Paclitaxel Eluting Stent in Postfibrinolysis Angioplasty
Acronym
GRACIA3
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2009
Overall Recruitment Status
Completed
Study Start Date
October 2004 (undefined)
Primary Completion Date
January 2008 (Actual)
Study Completion Date
January 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
GRACIA Group
Collaborators
Spanish Ministry of Health., Spanish Ministry of Science and Innovation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction
Keywords
ST elevation acute myocardial infarction, Thrombolysis, Early routine percutaneous coronary intervention, tirofiban, paclitaxel

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
436 (Actual)

8. Arms, Groups, and Interventions

Arm Title
bare-metal stent without tirofiban
Arm Type
Active Comparator
Arm Description
implantation of a bare-metal stent with no tirofiban infusion after fibrinolysis
Arm Title
bare-metal stent with tirofiban
Arm Type
Active Comparator
Arm Description
implantation of a bare-metal stent with tirofiban infusion after fibrinolysis
Arm Title
paclitaxel-eluting stent without tirofiban
Arm Type
Active Comparator
Arm Description
implantation of a paclitaxel eluting-stent with no tirofiban after fibrinolysis
Arm Title
paclitaxel-eluting stent with tirofiban
Arm Type
Active Comparator
Arm Description
implantation of a paclitaxel eluting-stent with tirofiban infusion after fibrinolysis
Intervention Type
Procedure
Intervention Name(s)
Postfibrinolysis percutaneous coronary intervention
Other Intervention Name(s)
Express stents (Boston Scientific, Natick, Massachusetts)
Intervention Description
implantation of a bare-metal stent with no infusion of tirofiban 120 minutes after fibrinolysis
Intervention Type
Procedure
Intervention Name(s)
Postfibrinolysis percutaneous coronary intervention
Other Intervention Name(s)
Express stents (Boston Scientific, Natick, Massachusetts)
Intervention Description
implantation of a bare-metal stent with infusion of tirofiban 120 minutes after fibrinolysis
Intervention Type
Procedure
Intervention Name(s)
Postfibrinolysis percutaneous coronary intervention
Other Intervention Name(s)
TAXUS stents (Boston Scientific)
Intervention Description
implantation of a paclitaxel eluting-stent with no infusion of tirofiban 120 minutes after fibrinolysis
Intervention Type
Procedure
Intervention Name(s)
Postfibrinolysis percutaneous coronary intervention
Other Intervention Name(s)
TAXUS stents (Boston Scientific)
Intervention Description
implantation of a paclitaxel eluting-stent with infusion of tirofiban 120 minutes after fibrinolysis
Primary Outcome Measure Information:
Title
to determine the efficacy of paclitaxel eluting stent compared to conventional bare stent in terms of restenosis
Time Frame
12 months
Title
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
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
to determine the safety of paclitaxel eluting stent in terms of rate of complications, and particularly acute and subacute total occlusion.
Time Frame
12 months
Title
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
Time Frame
12 months
Title
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.
Time Frame
12 months
Title
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
Time Frame
30 days
Title
to determine the efficacy of use of tirofiban in relation to time to fibrinolytic therapy and time to mechanical revascularization.
Time Frame
24 hours
Title
to determine possible interactions between the paclitaxel eluting stent and tirofiban in terms of restenosis or acute and subacute total occlusion following coronary stenting.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with ST-segment elevation acute myocardial infarction with all of the following criteria will be eligible for enrollment: Age >18 years. Chest discomfort >30 minutes with no response to nitroglycerin. Time from the onset of symptoms to randomization < 12 hours. 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. Killip class > 3. Written informed consent will be obtained. Exclusion Criteria: Patients presenting with any of the following will not be included in the study. 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. Suspected mechanical complications of acute myocardial infarction. Previous CABG. Non-cardiac disease that is likely to jeopardize the planned termination of the study. Woman of childbearing potential unless a negative pregnant test. Active bleeding and recent (within 2 weeks) surgery that contraindicate the use of heparin, tirofiban, or platelet aggregation inhibitors. 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 History of hypersensitivity to aspirin, ticlopidine, clopidogrel, heparin, tirofiban and stainless steel. Known renal failure, creatinine >2,5 mg/dL. Known impaired hepatic function that contraindicates the use of clopidogrel. Known thrombocytopenia (100.000). Participation in other trial. Known multivessel disease identified as no suitable for revascularization. Known peripheral vascular disease that difficult cardiac catheterization.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francisco Fernandez-Aviles, MD, PhD
Organizational Affiliation
ICICOR, Hospital Clínico Universitario Valladolid, Spain
Official's Role
Study Chair
Facility Information:
Facility Name
Instituto de Ciencias del Corazón (ICICOR). Hospital Clínico Universitario de Valladolid
City
Valladolid
ZIP/Postal Code
47005
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
20716757
Citation
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.
Results Reference
derived

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Role of Tirofiban and the Paclitaxel Eluting Stent in Postfibrinolysis Angioplasty

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