Facilitation Through Aggrastat By drOpping or Shortening Infusion Line in Patients With ST-segment Elevation Myocardial Infarction Compared to or on Top of PRasugrel Loading dOse (FABOLUS PRO)

Comparison of Multiple Oral and/or Intravenous Anti-platelet Strategies in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary PCI

This is a single-centre, open-label prospective randomized pharmacodynamic investigation of 2 antiplatelet regimens in patients undergoing coronary intervention for ST segment elevation myocardial infarction(STEMI):

1. Tirofiban bolus only or bolus followed by 2 hour infusion on top of 600 mg clopidogrel or 60 mg prasugrel.
2. Prasugrel given at 60 mg.

Study Overview

• Status: Completed
• Conditions: ST Segment Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Prasugrel; Drug: Tirofiban

Detailed Description

Primary hypothesis: Percentage IPA after 20uMol/ADP at 30' will be superior in the tirofiban arm (as aggregate) versus prasugrel alone arm Percentage IPA at 30' after 20uMol/ADP 90%±15 and 80%±15 in the tirofiban and prasugrel alone arm, respectively. For a power of 90% and an alpha error set at 5%, 50 patients per group have to be recruited.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Ferrara, Italy, 44100
    • Cardiology Unit

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:

• Chest pain for >30 min with an electrocardiographic ST-segment elevation more than 1 mm in two or more contiguous electrocardiogram (ECG) leads, or with a new left bundle-branch block, and admission either within 12 h of symptom onset or between 12 and 24 h after onset with evidence of continuing ischemia

Exclusion Criteria:

• Administration of fibrinolytic or any GP IIbIIIa inhibitors for the treatment of current AMI or within 1 month before history of bleeding diathesis
• Known sensitivity to abciximab, to any component of the product or to murine monoclonal antibodies
• Major surgery or trauma within 30 days
• Active bleeding
• Previous stroke in the last six months
• Oral anticoagulant therapy
• Pre-existing thrombocytopenia
• Vasculitis
• Hypertensive retinopathy
• Severe hepatic failure
• Severe renal failure requiring haemodialysis
• Documented allergy/intolerance or contraindication to clopidogrel or inability to assume clopidogrel on a consecutive daily basis for a minimum of 30 days, or to heparin or aspirin
• Uncontrolled hypertension (systolic or diastolic arterial pressure >180 mmHg or 120, respectively, despite medical therapy)
• Limited life expectancy, e.g. neoplasms, others
• Inability to obtain informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: prasugrel; Prasugrel 60 mg loading dose	Drug: Prasugrel; 60 mg loading dose given orally at presentation
Active Comparator: Tirofiban; Tirofiban will be at a bolus only of 25uM or followed by 2 hour infusion	Drug: Tirofiban; Tirofiban will be given at high bolus dose only of bolus followed by 2 H infusion in a randomized manner (1:1 ratio).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage IPA after 20uMol/ADP at 30' will be superior in the tirofiban arm (as aggregate) versus prasugrel alone arm	Platelet aggregation (PA) will be performed as previously reported [J Am Coll Cardiol 2006;48:2178-85]. Blood samples anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) (Alfa Wasserman, Bologna, Italia) and aggregation will be assessed using a AggRAM Advanced Modular System light transmittance aggregometer.	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage IPA at 15 minutes after ADP or TRAP induced platelet aggregation via traditional light transmission aggregometry.	Blood samples draen at 15', 30', 1H, 2H, 6H and 18-24H, anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) and 5 and 15 TRAP.	15 minutes
Clinical outcomes	Death, Myocardial infarction, stroke and the need for target vessel revascularisation will be monitored up to 1 year	1 year
Percentage IPA at 1 hour after ADP or TRAP induced platelet aggregation via traditional light transmission aggregometry.	Blood samples draen at 15', 30', 1H, 2H, 6H and 18-24H, anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) and 5 and 15 TRAP.	1 hour
Percentage IPA at 2 hours after ADP or TRAP induced platelet aggregation via traditional light transmission aggregometry.	Blood samples draen at 15', 30', 1H, 2H, 6H and 18-24H, anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) and 5 and 15 TRAP.	2 hours
Percentage IPA at 6 hours after ADP or TRAP induced platelet aggregation via traditional light transmission aggregometry.	Blood samples draen at 15', 30', 1H, 2H, 6H and 18-24H, anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) and 5 and 15 TRAP.	6 hours
Percentage IPA at 18-24 hours after ADP or TRAP induced platelet aggregation via traditional light transmission aggregometry.	Blood samples draen at 15', 30', 1H, 2H, 6H and 18-24H, anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) and 5 and 15 TRAP.	18-24 hours

Collaborators and Investigators

• Sponsor: Università degli Studi di Ferrara

Publications and helpful links

General Publications

• Valgimigli M, Tebaldi M, Campo G, Gambetti S, Bristot L, Monti M, Parrinello G, Ferrari R; FABOLUS PRO Investigators. Prasugrel versus tirofiban bolus with or without short post-bolus infusion with or without concomitant prasugrel administration in patients with myocardial infarction undergoing coronary stenting: the FABOLUS PRO (Facilitation through Aggrastat By drOpping or shortening Infusion Line in patients with ST-segment elevation myocardial infarction compared to or on top of PRasugrel given at loading dOse) trial. JACC Cardiovasc Interv. 2012 Mar;5(3):268-77. doi: 10.1016/j.jcin.2012.01.006.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: April 13, 2011
• First Submitted That Met QC Criteria: April 14, 2011
• First Posted (Estimate): April 15, 2011

Study Record Updates

• Last Update Posted (Estimate): October 10, 2012
• Last Update Submitted That Met QC Criteria: October 9, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Prasugrel; Clopidogrel; Tirofiban; glycoprotein IIa/IIIa inhibitors; P2Y12 blockers
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Tirofiban; Prasugrel Hydrochloride
• Other Study ID Numbers: FAB-PRO-I