Clinical trial NCT02268669: Comparison of Primary PCI vs. Post-thrombolysis PCI as Reperfusion Strategies in STEMI
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Myocardial Infarction
Keywords: primary angioplasty
post-thrombolysis angioplasty
ST elevation acute myocardial infarction
Lead sponsor: GRACIA Group
Sponsor class: OTHER
First posted: 2014-10-20
Enrollment: 1444
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: incidence of the composite endpoint formed by death, reinfarction, new revascularization, rehospitalization or severe hemorrhage
timeFrame: 12 months
Secondary outcomes:
measure: Incidence of death
timeFrame: 12 months
measure: Incidence of myocardial reinfaction
timeFrame: 12 months
measure: Incidence of new revascularization
timeFrame: 12 months
measure: Incidence of rehospitalization
timeFrame: 12 months
measure: Incidence of cardiovascular mortality
timeFrame: 12 months
measure: Incidence of the composite endpoint formed by death, reinfarction, new revascularization, rehospitalization and/or hemorrhage
timeFrame: 30 days
measure: Incidence of major bleeding events
timeFrame: Hospitalization and at 30 days
measure: 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)
timeFrame: 12 months
measure: Incidence of the composite endpoint formed by death, reinfarction, new revascularization, rehospitalization and/or hemorrhage
timeFrame: 3 years
measure: Incidence of death
timeFrame: 3 years
measure: Incidence of reinfarction
timeFrame: 3 years
measure: Incidence of new revascularization
timeFrame: 3 years
measure: Incidence of rehospitalization
timeFrame: 3 years
measure: Analysis of stent thrombosis according to the Academic Research Consortium (ARC) definition (http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4253t2.rtf.)
timeFrame: 30 days, 12 months and 3 years
measure: 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
timeFrame: 30 days, 12 months and 3 years
measure: 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
timeFrame: 30 days, 12 months and 3 years
measure: 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
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: faviles@secardiologia.es
name: Francisco Fernandez-Aviles, MD, PhD
role: STUDY_CHAIR
References:
citation: Fernandez-Aviles F, Alonso JJ, Castro-Beiras A, Vazquez N, Blanco J, Alonso-Briales J, Lopez-Mesa J, Fernandez-Vazquez F, Calvo I, Martinez-Elbal L, San Roman JA, Ramos B; GRACIA (Grupo de Analisis de la Cardiopatia Isquemica 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. doi: 10.1016/S0140-6736(04)17059-1.
citation: Fernandez-Aviles F, Alonso JJ, Pena G, Blanco J, Alonso-Briales J, Lopez-Mesa J, Fernandez-Vazquez F, Moreu J, Hernandez RA, Castro-Beiras A, Gabriel R, Gibson CM, Sanchez PL; GRACIA-2 (Groupo de Analisis de Cardiopatia Isquemica 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. doi: 10.1093/eurheartj/ehl461. Epub 2007 Jan 23.
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.