FATA: Randomized Study on Facilitated Angioplasty With Tirofiban or Abciximab
The elective("standard of care") treatment of ST - elevation acute myocardial infarction (STEMI) currently consists of primary angioplasty with stent implantation during administration of Abciximab, a inhibitor of GP IIb/IIIa platelet receptor.
Tirofiban is another potent inhibitor of GP IIb/IIIa platelet receptor with an efficacy on platelet aggregation inhibition equal to or greater than Abciximab if a high dose bolus is used, i.e. 25 microg/kg, (platelet aggregation inhibition > 90% 15 minutes after infusion). It can therefore be hypothesized that this drug can improve the results of primary angioplasty to the same extent as Abciximab.
The aim of this study is to compare the efficacy, in terms of myocardial reperfusion indices, of Abciximab and high dose of Tirofiban in primary angioplasty for STEMI, both in the case of treatment before transfer and of treatment in the catheterization laboratory during the procedure.
The reference hypothesis for the study objective is the equivalence or the non-inferiority of Tirofiban with respect to Abciximab.
Acute Myocardial Infarction
Drug: tirofiban high-bolus dose regimen
|Study Design:||Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||FATA: Comparison Between Tirofiban and Abciximab in Facilitated Angioplasty With Stent Implantation: Randomized Multicentre Study|
- ST resolution [ Time Frame: 90 minutes after opening of the IRA ] [ Designated as safety issue: No ]
- Patency of the IRA [ Time Frame: at the first selective angiography ] [ Designated as safety issue: No ]
- No reflow [ Time Frame: during the procedure ] [ Designated as safety issue: No ]
- TIMI 3 flow [ Time Frame: at the end of the procedure ] [ Designated as safety issue: No ]
- Myocardial blush grade [ Time Frame: at the end of the procedure ] [ Designated as safety issue: No ]
- Contractile recovery assessed with total FE and WMSI measured by echocardiography [ Time Frame: at 48 hours and 30 days ] [ Designated as safety issue: No ]
- MACE (death, reinfarction*, urgent TVR) [ Time Frame: at 30 days ] [ Designated as safety issue: No ]
- MACE (death, reinfarction*, TVR) [ Time Frame: One year ] [ Designated as safety issue: No ]
- Major bleeding requiring transfusion or surgery, or a reduction in Hb of more than 5 g%. [ Time Frame: in-hospital ] [ Designated as safety issue: Yes ]
- Intracranial hemorrhage. [ Time Frame: in-hospital ] [ Designated as safety issue: Yes ]
- Symptoms associated with new ECG alterations and a new increase in myocardial enzymes [ Time Frame: in-hospital ] [ Designated as safety issue: No ]
- Need for a new PTCA or CABG [ Time Frame: In-hospital, 30 days, one year ] [ Designated as safety issue: No ]
|Study Start Date:||June 2003|
|Study Completion Date:||September 2007|
|Primary Completion Date:||September 2007 (Final data collection date for primary outcome measure)|
Drug: tirofiban high-bolus dose regimen
bolus of 25 mcg/kg of body weight, followed by 18 hours infusion of 0.15 mcg/kg/min.
Other Name: Aggrastat
Active Comparator: 2
bolus of 0.25 mg/kg of body weight, followed by 12 hours infusion of 0.125 mcg/kg per minute
Other Name: Reopro
The Facilitated Angioplasty with Tirofiban or Abciximab Study (FATA Study) is a prospective multicentre study, randomized in 2 groups (high dose Tirofiban or Abciximab), on a sample of 700 patients with acute myocardial infarction for whom primary angioplasty is indicated. Patients will be enrolled in the Emergency Room or in the Intensive Care Unit and other hospital departments or externally in the event of intervention by the Emergency Ambulance Service 118. For all these patients it must be possible to administer a IIb/IIIa inhibitor immediately after ECG and clinical diagnosis, before transfer to the cath lab for the primary angioplasty procedure. Patients arriving directly in the cath lab without being randomized before transfer will also be included.
Major exclusion criteria are: Complete left bundle branch block, Previous myocardial infarction at the same site, Post-anoxic coma, Known thrombocytopenia or leucopenia, Previous episodes of hemorrhagic diathesis or allergy to ASA or thienopyridine; Anticoagulant therapy with dicumarol with INR > 2; Previous treatment with thrombolytics (within the previous 48 hours).
Randomization will take place as soon as possible after the diagnostic ECG and will be performed by means of a centralized automatic system using SMS messages sent by ordinary cell phones.
The primary endpoint is ST resolution 90 minutes after opening of the affected vessel. Secondary endpoints include: Patency of the vessel at the first selective angiography, no reflow phenomenon during the procedure, TIMI 3 flow at the end of the procedure, MACE (death, reinfarction*, urgent TVR°) at 30 days, MACE (death, reinfarction*, TVR°) at 6 months, major bleeding requiring transfusion or surgery, or a reduction in Hb of more than 5 g%, Ictus and intracranial hemorrhage.
To demonstrate the study hypothesis, i.e. that Tirofiban is equivalent to Abciximab in facilitating primary angioplasty in acute myocardial infarction, with sufficient statistical significance, the necessary number of patients for each drug was calculated on the basis of the methods used in equivalence studies and was fixed in 350 pts per group.
390 patients have been randomized (as of Sept 15th, 2006). Results are expected by the end of 2007.
This study will establish whether in primary angioplasty a high dose of Tirofiban has an equivalent effect to Abciximab, first in terms of microcirculation protection and then of long-term clinical results. If this hypothesis is confirmed, Tirofiban could be used as an alternative to Abciximab, with considerable savings given its much lower cost.
|Laboratorio Di Emodinamica, Istituto Di Cardiologia, Azienda Ospedaliera S.Orsola Malpighi|
|Bologna, BO, Italy, 40138|
|Divisione Di Cardiologia, Ospedale Maggiore|
|Bologna, BO, Italy, 40100|
|Azienda Ospedaliera Universitaria Policlinico|
|Modena, MO, Italy, 41100|
|Divisione Di Cardiologia, Ospedale S.Maria Nuova|
|Reggio Emilia, RE, Italy, 42100|
|Divisione Di Cardiologia, Ospedale Per Gli Infermi|
|Rimini, RN, Italy, 47900|
|Divisione Di Cardiologia Ii, Ospedale Policlinico Le Molinette|
|Torino, TO, Italy, 10100|
|Principal Investigator:||ANTONIO MARZOCCHI, MD||ISTITUTO DI CARDIOLOGIA, AZIENDA OSPEDALIERA S.ORSOLA-MALPIGHI, BOLOGNA|