Efficacy of Abciximab Bolus Only Regimen in Providing Inhibition of Platelet Action Over Time (FABOLUS)

Facilitation Through Abciximab By drOpping Infusion Line in Patients Undergoing Coronary Stenting. SYNergy With Clopidogrel at High Loading dOse Regimen

In full responders to clopidogrel scheduled to undergo PCI for NSTEACS, the use of abciximab bolus only plus 600 mg clopidogrel loading dose will result in a non-inferior inhibition of platelet aggregation after 4 hours as measured by LTA (20micromol ADP) when compared with abciximab plus infusion and 300 mg clopidogrel loading dose.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: bolus+infusion; Drug: abciximab bolus only regimen

Detailed Description

Based on the outcome of the EPIC trial, and the sub-optimal results with a single abciximab bolus compared with bolus and infusion, it was recommended to prolong platelet inhibition by a 12h infusion of abciximab after the initial bolus administration in patients undergoing percutaneous coronary intervention (PCI). However, lower outcomes in the single bolus group in the EPIC study were entirely driven by the rates of urgent repeat revascularization at 30 days (3•6 percent bolus group versus 0•8 percent bolus and infusion group, p < 0.001), a complication probably related to the lack of stent use at that time. Importantly, there was no significant difference in terms of death or myocardial infarction (MI). Moreover, the use of clopidogrel in patients undergoing coronary stenting may currently reduce the need for infusion after a single abciximab bolus and it is likely that the soon to come availably of even more potent oral thienopyridines with faster onset of action such as prasugrel may further contribute to make post-bolus abciximab infusion of marginal clinical benefit. Yet, it is known that infusion, as compared to bolus only regimen increases the bleeding rate and the incidence of thrombocytopenia. Thus, bolus only regimen has the potential to maintain protection from ischemic complications in patients undergoing PCI while optimizing the safety profile of the treatment in the current era of intervention based on stents and thienopyridines with fast onset of action.

The CLEAR-PLATELETS study has recently shown that 600 mg clopidogrel does not affect the degree of platelet inhibition throughout infusion of eptifibatide, which is consistent with the notion that glycoprotein IIb/IIIa inhibition at steady state leads to near maximal platelet blockade. No study has so far investigated the effect of clopidogrel, given at high loading dose, in patients treated with abciximab bolus only. In particular, it is not known whether the administration of clopidogrel at high loading dose may prolong the effect of abciximab bolus on the degree of platelet inhibition and if so at which time point the combination of abciximab bolus and clopidogrel may become suboptimal in terms of platelet inhibition as compared to currently recommended 12h infusion of abciximab after the initial bolus administration. This information would lead to relevant clinical implications as it may define the time frame for a safe and effective intervention after bolus only of abciximab in current practice.

This is a single-centre, double-blind prospective randomized pharmacodynamic investigation of 2 antiplatelet regimens in patients undergoing coronary stenting for non-ST segment elevation acute coronary syndromes (NSTECACS):

1. Abciximab bolus followed by infusion plus on-label clopidogrel administration at 300 mg loading dose.
2. abciximab bolus without infusion plus high loading dose of clopidogrel at 600 mg

The objective of the investigation is to test the hypothesis that the administration of abciximab bolus only plus high loading dose of clopidogrel at 600 mg will provide a non inferior level of inhibition of platelet aggregation 4 hours after administration as compared to abciximab bolus followed by standard infusion in combination with clopidogrel loading dose of 300 mg in patients with normal response to clopidogrel (as evaluated after 14-30 days).

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Ferrara, Italy, 44100
    • Institue of Cardiology, University of Ferrara

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:

Both of the following:

• Age >18 years
• Symptoms of ischemia that were increasing or occurred at rest, with the last episode occurring no more than 24 hours before randomization;

AND at least one of the following:

• An elevated cardiac troponin T level (≥0.015 μg per liter);
• The presence of ischemic changes as assessed by electrocardiography (defined as ST-segment depression or transient ST-segment elevation exceeding 0.05 mV, or T-wave inversion of ≥0.2 mV in two contiguous leads)
• A documented history of coronary artery disease as evidenced by previous myocardial infarction, findings on previous coronary angiography, or a positive exercise test.

Exclusion Criteria:

• The exclusion criteria are:
• administration of fibrinolytic or any GP IIb IIIa inhibitors for the treatment of current AMI or within 1 month before it
• 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
• pregnancy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Abciximab bolus plus infusion; Abciximab bolus of 0.25mg /Kg, followed by a 12-h infusion 0.125 microg/Kg/min (to a maximum of 10 µg/min) and immediate clopidogrel at 300 mg loading regimen.	Drug: bolus+infusion; Abciximab bolus of 0.25mg /Kg, followed by a 12-h infusion 0.125 microg/Kg/min (to a maximum of 10 µg/min) and immediate clopidogrel at 300 mg loading regimen
Experimental: bolus only regimen; Abciximab bolus of 0.25mg /Kg followed by placebo infusion and immediate clopidogrel at 600 mg loading dose	Drug: abciximab bolus only regimen; Abciximab bolus of 0.25mg /Kg followed by placebo infusion and immediate clopidogrel at 600 mg loading dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
In responders to clopidogrel: Inhibition of platelet aggregation at peak 4h after administration of study drugs measured by LTA (stimulated with 20micromolar ADP)	4 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
In all patients treated and in the responders to clopidogrel: • Inhibition of platelet aggregation in the two study groups at time points different from 4 hours after abciximab bolus measured by LTA	up to 24 hours
MACE rate	30 days
Bleeding rates	30 days
Thrombocytopenia	30 days

Collaborators and Investigators

• Sponsor: Università degli Studi di Ferrara

Publications and helpful links

General Publications

• Valgimigli M, Campo G, Tebaldi M, Monti M, Gambetti S, Scalone A, Parrinello G, Ferrari R; Fabolus Synchro (facilitation through abciximab by dropping infusion Line in patients undergoing coronary stenting. Synergy with clopidogrel at high loading dose regimen) Investigators. Randomized, double-blind comparison of effects of abiciximab bolus only vs. on-label regimen on ex vivo inhibition of platelet aggregation in responders to clopidogrel undergoing coronary stenting. J Thromb Haemost. 2010 Sep;8(9):1903-11. doi: 10.1111/j.1538-7836.2010.03972.x.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: June 26, 2009
• First Submitted That Met QC Criteria: June 26, 2009
• First Posted (Estimate): June 29, 2009

Study Record Updates

• Last Update Posted (Estimate): June 29, 2009
• Last Update Submitted That Met QC Criteria: June 26, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: Acute coronary syndrome; Bolus; Abciximab; Infusion; platelet inhibition; Non ST segment elevation acute coronary syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Platelet Aggregation Inhibitors; Anticoagulants; Abciximab
• Other Study ID Numbers: FAS-07-I

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No