Bivalirudin/Prasugrel Versus Abciximab/Clopidogrel in Patients Presenting With STEMI

Bivalirudin Plus Prasugrel vs Abciximab Plus Clopidogrel. Optimizing Ischemic Protection and Bleeding Risk in Patients With ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

In the setting of ST elevation myocardial infarction newer therapies has been recently studied and, following encouraging results, introduced into the clinical practice. Prasugrel showed to be a valid alternative to overcome limitation of clopidogrel therefore providing a better ischemic protection. On the other hand, bivalirudin is at least as beneficial as heparin/abciximab as anticoagulant agent but associated with fewer hemorrhagic events. The primary hypothesis of the study is that the combination of prasugrel plus bivalirudin can be associated with a better risk/benefit profile.

Study Overview

• Status: Unknown
• Conditions: ST-Elevation Myocardial Infarction; Primary Percutaneous Coronary Intervention
• Intervention / Treatment: Drug: prasugrel/bivalirudin; Drug: clopidogrel/abciximab

Detailed Description

Background:

In the setting of STEMI, adjunctive pharmacological therapy plays a key role in the acute management. Along with the clear benefit of mechanical reperfusion strategies, several drugs showed to be beneficial. On top of clopidogrel, heparins and IIB/IIIa glycoprotein, other drugs have been recently introduced showing encouraging results. These "new" drugs, namely prasugrel and bivalirudin, have only been compared separately.

Primary hypothesis: the combination of prasugrel/bivalirudin is superior to the combination of clopidogrel and heparin/abciximab in terms of net adverse clinical events, i.e. ischemic events plus hemorrhagic events

Setting:

- patients presenting with ST-elevation myocardial infarction undergoing primary PCI

Mechanical reperfusion:

-primary percutaneous coronary intervention

Pharmacological Interventions:

- Two arms: Clopidogrel plus heparin/abciximab vs Prasugrel plus Bivalirudin

Follow up:

- 1 year

Measurements:

• efficacy end points in terms of reduction of ischemic events
• safety end points in terms of reduction of bleeding events

• Study Type: Interventional
• Enrollment (Anticipated): 800
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20149
    • Istituto Clinico S. Ambrogio
    • Principal Investigator: Luca Testa, Md, PhD

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:

• ST elevation myocardial infarction
• No contraindication to primary PCI

Exclusion Criteria:

• Known intolerance/allergy to one of the study drugs or their components
• Clinical indication to treatment with oral anticoagulant, including use of warfarin or dabigatran or other oral anticoagulant agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: prasugrel/bivalirudin; 60 mg loading dose of prasugrel will be followed by maintenance dose of 10mg (or 5mg according to body weight and age). During primary PCI, Bivalirudin will be used as anticoagulant (bolus plus infusion), on a weight-adjusted dose.	Drug: prasugrel/bivalirudin; 60mg loading dose followed by 10mg or 5 mg (according to body weight or age)maintenance dose of prasugrel. Bivalirudin during the primary PCI (bolus plus infusion); Other Names: Efient; Angiox
ACTIVE_COMPARATOR: clopidogrel/abciximab; 600mg loading dose of clopidogrel will be followed by 75mg maintenance dose. During primary PCI abciximab (bolus plus infusion) will be used as anticoagulant.	Drug: clopidogrel/abciximab; 600mg loading dose of clopidogrel followed by 75mg maintenance dose. Abciximab will be used during primary PCI, bolus plus infusion.; Other Names: Plavix; ReoPro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major adverse cardiovascular events	Combined outcome of overall death, non fatal MI, major stroke	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major bleedings	according to TIMI major bleedings definition	1 year
minor bleedings	according to TIMI minor bleedings definition	1 year
stent thrombosis	according to ARC definition of probable/definite stent thrombosis	1 year
overall death		1 year
non fatal myocardial infarction	defined according to current guidelines	1 year
ischemic stroke		1 year

Collaborators and Investigators

• Sponsor: Istituto Clinico Sant'Ambrogio
• Collaborators: Istituto Clinico Humanitas; Azienda Ospedaliera Niguarda Cà Granda; Centro Cardiologico Monzino
• Investigators: Principal Investigator: Luca Testa, MD,PhD, Istituto Clinico S. Ambrogio; Study Director: Fracensco Bedogni, MD, Istituto Clinico S. Ambrogio

Publications and helpful links

General Publications

• Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM, McCabe CH, Antman EM; TRITON-TIMI 38 investigators. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet. 2009 Feb 28;373(9665):723-31. doi: 10.1016/S0140-6736(09)60441-4.
• Mehran R, Lansky AJ, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Kornowski R, Hartmann F, Gersh BJ, Pocock SJ, Wong SC, Nikolsky E, Gambone L, Vandertie L, Parise H, Dangas GD, Stone GW; HORIZONS-AMI Trial Investigators. Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial. Lancet. 2009 Oct 3;374(9696):1149-59. doi: 10.1016/S0140-6736(09)61484-7. Epub 2009 Aug 28.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ANTICIPATED): June 1, 2011
• Study Completion (ANTICIPATED): June 1, 2011

Study Registration Dates

• First Submitted: June 25, 2010
• First Submitted That Met QC Criteria: July 7, 2010
• First Posted (ESTIMATE): July 8, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 8, 2010
• Last Update Submitted That Met QC Criteria: July 7, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: STEMI; Primary PCI; anticoagulants; antiplatelets
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Clopidogrel; Bivalirudin; Prasugrel Hydrochloride; Abciximab
• Other Study ID Numbers: Biva/Pra versus Abcix/clop (REGISTRY: Milan STEMI registry); B/P vs A/C for STEMI (REGISTRY: Milan STEMI registry)