Comparison of Primary PCI vs. Post-thrombolysis PCI as Reperfusion Strategies in STEMI

Myocardial Infarction Clinical Trial

— GRACIA4  

Official title:

A Randomized Clinical Trial Comparing Primary PCI and Post-thrombolysis PCI as Reperfusion Strategies in Patients With ST Segment Elevation Acute Myocardial Infarction

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02268669
• Other study ID #: GRACIA4
• Status: Active, not recruiting
• Phase: Phase 4
• First received: October 13, 2014
• Last updated: October 16, 2014
• Start date: May 2010
• Est. completion date: March 2016

Study information

• Verified date: October 2014
• Source: GRACIA Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

The conceptual hypothesis of this study is that primary angioplasty is superior to a combined strategy of immediate thrombolysis followed by routine angioplasty in patients with ST-segment elevation acute myocardial infarction (STEMI), even with the inherent delay of the transfer of these patients.

Description:

This is a randomized, multicenter, open-label clinical trial comparing two strategies of reperfusion in STEMI. Patients will be randomly allocated to: primary angioplasty or post-thrombolysis angioplasty. A clinical follow-up will be performed at 12 months. In this trial, 1444 patients with STEMI will be randomized to primary angioplasty with immediate stent implantation in at least the infarct related artery (IRA) under bivalirudin protection, or to a combined strategy of immediate thrombolysis with tenecteplase (TNK) and enoxaparin followed by cardiac catheterization and adequate revascularization when indicated during the next morning after randomization.

Primary endpoint:

To compare the clinical efficacy (incidence of the composite endpoint formed by death, reinfarction, new revascularization, rehospitalization or severe hemorrhage within 12 months) of primary angioplasty versus thrombolytic treatment followed by percutaneous coronary intervention (PCI) the next day in patients with STEMI.

Secondary endpoints:

• Components of the composite endpoint individually analysed at 12 months (death, reinfarction, new revascularization, rehospitalization and severe hemorrhage).

• Cardiovascular mortality and its different components (pre-specified in the case report forms, CRF) at 12 months.

• Incidence of the composite endpoint formed by death, reinfarction, new revascularization, rehospitalization and/or hemorrhage at 30 days.

• Incidence of major bleeding events during hospitalization and at 30 days.

• To compare the clinical efficacy of both treatments according to the timing of presentation after symptom onset (0 to 3 hours, >3-6 hours, and >6-12 hours), to the patient´s age (> or < 75 years), to the infarction localization (anterior or inferior), to gender (male or female), to the presence of diabetes mellitus and to the characteristics of the recruiting center (with or without 24-hour catheterization facilities).

• Incidence of the composite endpoint formed by death, reinfarction, new revascularization, rehospitalization and/or hemorrhage at 3 years.

• Components of the composite endpoint individually analysed at 3 years (death, reinfarction, new revascularization, rehospitalization and severe hemorrhage).

• Analysis of stent thrombosis according to the Academic Research Consortium (ARC) definition (http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4253t2.rtf.) within 30 days, 12 months and 3 years.

• To compare the combination of death, reinfarction, revascularization, rehospitalization and/or major hemorrhage of patients treated with primary angioplasty versus those assigned to the postrombolysis angioplasty who underwent catheterization the following day within 30 days, 12 months and 3 years.

• To compare every indivicual components of the combine endpoint (death, reinfarction, revascularization, rehospitalization and major hemorrhage) of patients treated with primary angioplasty versus those assigned to the postrombolysis angioplasty who underwent catheterization the following day within 30 days, 12 months and 3 years.

• To compare the cost-effectiveness relationship (cost of maintaining a patient alive and without adverse cardiovascular events within the first year post-infarction) of both strategies.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1444
• Est. completion date: March 2016
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >18 years

• Chest discomfort > 30 minutes with no response to nitroglycerin

• Time from the onset of symptoms to randomization between 0 and 12 hours

• ST segment elevation > 1 mm in two or more contiguos precordial leads or non-diagnostic ECG (left bundle branch block or pacemarker rhythm) with classic symptoms.

• Killip class equal or less than 3

• Written informed consent

Exclusion Criteria:

• Cardiogenic shock defined as a systolic blood pressure <90 mm Hg without response to fluid administration or <100 mm Hg in patients with supportive treatment and no bradycardia

• Suspicion or evidence of mechanical complications of STEMI

• Non-cardiac disease that is likely to jeopardize compliance with follow-up schedule of the study (life expectancy < 1 year)

• woman of childbearing potential unless a negative pregnant test

• Major contraindications for thrombolytic therapy

• Participation in other trial

• Known multivessel disease identified as unsuitable for revascularization

• Known peripheral vascular disease that complicates cardiac catheterization

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Other:
• Reperfusion strategies
Two different reperfusion strategies in STEMI will be compared: primary angioplasty vs. post-thrombolysis angioplasty

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
GRACIA Group

References & Publications (3)

Fernandez-Avilés F, Alonso JJ, Castro-Beiras A, Vázquez N, Blanco J, Alonso-Briales J, López-Mesa J, Fernández-Vazquez F, Calvo I, Martínez-Elbal L, San Román JA, Ramos B; GRACIA (Grupo de Análisis de la Cardiopatía Isquémica Aguda) Group. Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial. Lancet. 2004 Sep 18-24;364(9439):1045-53. — View Citation

Fernández-Avilés F, Alonso JJ, Peña G, Blanco J, Alonso-Briales J, López-Mesa J, Fernández-Vázquez F, Moreu J, Hernández RA, Castro-Beiras A, Gabriel R, Gibson CM, Sánchez PL; GRACIA-2 (Groupo de Análisis de Cardiopatía Isquémica Aguda) Investigators. Primary angioplasty vs. early routine post-fibrinolysis angioplasty for acute myocardial infarction with ST-segment elevation: the GRACIA-2 non-inferiority, randomized, controlled trial. Eur Heart J. 2007 Apr;28(8):949-60. Epub 2007 Jan 23. — View Citation

Sánchez PL, Gimeno F, Ancillo P, Sanz JJ, Alonso-Briales JH, Bosa F, Santos I, Sanchis J, Bethencourt A, López-Messa J, de Prado AP, Alonso JJ, San Román JA, Fernández-Avilés 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	incidence of the composite endpoint formed by death, reinfarction, new revascularization, rehospitalization or severe hemorrhage	To compare the clinical efficacy (incidence of the composite endpoint formed by death, reinfarction, new revascularization, rehospitalization or severe hemorrhage within 12 months) of primary angioplasty versus post-thrombolytic angioplasty	12 months	Yes
Secondary	Incidence of death	Components of the composite endpoint individually analysed at 12 months (death, reinfarction, new revascularization, rehospitalization and severe hemorrhage).	12 months	Yes
Secondary	Incidence of myocardial reinfaction	Components of the composite endpoint individually analysed at 12 months (death, reinfarction, new revascularization, rehospitalization and severe hemorrhage).	12 months	Yes
Secondary	Incidence of new revascularization	Components of the composite endpoint individually analysed at 12 months (death, reinfarction, new revascularization, rehospitalization and severe hemorrhage).	12 months	Yes
Secondary	Incidence of rehospitalization	Components of the composite endpoint individually analysed at 12 months (death, reinfarction, new revascularization, rehospitalization and severe hemorrhage).	12 months	Yes
Secondary	Incidence of cardiovascular mortality		12 months	Yes
Secondary	Incidence of the composite endpoint formed by death, reinfarction, new revascularization, rehospitalization and/or hemorrhage		30 days	Yes
Secondary	Incidence of major bleeding events		Hospitalization and at 30 days	Yes
Secondary	clinical efficacy according to timing of presentation (<3, 3-6, and >6 hours), patient´s age (> or < 75 years), infarction localization, gender, presence of diabetes and recruiting center (with or without catheterization facilities)		12 months	Yes
Secondary	Incidence of the composite endpoint formed by death, reinfarction, new revascularization, rehospitalization and/or hemorrhage		3 years	Yes
Secondary	Incidence of death		3 years	Yes
Secondary	Incidence of reinfarction		3 years	Yes
Secondary	Incidence of new revascularization		3 years	Yes
Secondary	Incidence of rehospitalization		3 years	Yes
Secondary	Analysis of stent thrombosis according to the Academic Research Consortium (ARC) definition (http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4253t2.rtf.)		30 days, 12 months and 3 years	Yes
Secondary	Combination of death, reinfarction, revascularization, rehospitalization and/or major hemorrhage of patients treated with primary angioplasty vs. those assigned to postrombolysis angioplasty undergoing catheterization the following day		30 days, 12 months and 3 years	Yes
Secondary	To compare every indivicual components of the combine endpoint of patients treated with primary angioplasty versus those assigned to the postrombolysis angioplasty who underwent catheterization the following day		30 days, 12 months and 3 years	Yes
Secondary	To compare the cost-effectiveness relationship (cost of maintaining a patient alive and without adverse cardiovascular events within the first year post-infarction) of both strategies		12 months	No