Tirofiban and Enoxaparin in High Risk Coronary Intervention

High Bolus Dose Tirofiban and Enoxaparin Provides Reduced Thrombin Generation and Inflammatory Markers in Patients With High Risk Undergoing Percutaneous Intervention

Patients undergoing coronary angioplasty are frequently treated with new drugs that stop blood platelets working and so improve the success of the procedure. Individual patients may vary in the dose of the drug required. New platelet tests have been developed which can be performed near the patient and possibly immediately tell the doctor the degree of platelet inhibition achieved so that the dose can be adjusted accordingly. This study aims to investigate if these platelet tests indicate if new anticoagulants are more effective at inhibiting platelet function than the traditional anticoagulants. The study will demonstrate if these newer drugs improve blood flow through the heart muscle and thereby provide better long term outcomes for patients undergoing percutaneous intervention.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Tirofiban; Drug: unfractionated heparin; Drug: Enoxaparin

Detailed Description

Objectives: The study assessed the benefit of high bolus dose tirofiban with enoxaparin compared to unfractionated heparin.

Introduction: The benefit of the use of glycoprotein IIb/IIa inhibitors with low molecular weight heparins in high risk patients undergoing percutaneous intervention (PCI) over traditional unfractionated heparin (UFH) is debated. Methods; The study is a prospective single center open-label trial of patients with high-risk acute coronary syndrome treated with PCI who were randomised to anticoagulation with UFH or enoxaparin with 'high dose' (25 mcg/kg bolus) tirofiban This study measured a panel of platelet activation markers, inflammatory biomarkers and thrombus generation between the two groups.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4032
      • The Prince Charles Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients were recruited from those undergoing PCI with a planned placement of an intracoronary stent
• Including patients with unstable angina pectoris, acute coronary syndrome or NSTEMI
• Experienced ischaemic pain at rest
• Lasting 10 minutes and occurring within 7 days before enrollment
• As well as one of the following: ECG changes: New or presumably new ST-segment depression greater than or equal to 0.1 mV (1 mm), or transient (< 30 minutes) ST-segment elevation greater than or equal to 0.1 mV (1 mm) in at least 2 contiguous leads
• Abnormal cardiac enzymes within the 24 hours before enrollment, defined as elevated Troponin I defined as elevated Troponin I (above the normal reference -High-risk angiographic features that included intraluminal filling defect, angiographically visible thrombus eccentric lesion, type, location in a proximal major vessel and thrombolysis in myocardial infarction (TIMI) flow of II or less

Exclusion Criteria:

• Increased bleeding risk: ischaemic stroke within the last year or any previous haemorrhagic stroke, tumour or intracranial aneurysm;
• Recent (<1 month) trauma or major surgery (including bypass surgery);
• Active bleeding
• Unexplained clinically significant bleeding, thrombocytopenia (platelet count < 100 x 109/L) or history of thrombocytopenia with GP IIb/IIIa, heparin or enoxaparin therapy
• Angina from secondary causes such as severe uncontrolled hypertension (systolic blood pressure > 180 mm Hg despite treatment)
• Valvular disease, congenital heart disease, hypertrophic cardiomyopathy, -Thrombolytic therapy within preceding 24 hours
• Receiving antiIIb/IIIa therapy
• Creatinine clearance of <30 mL/min

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 High dose tirofiban and enoxaparin; Enoxaparin was administered at the commencement of PCI at a dose of 0.75 mg/kg . Tirofiban was administered once the wire had crossed the lesion during PCI with a bolus dose of 25 µg/kg of bodyweight, followed by an infusion of 0.15 µg per kilogram per minute for 18 to 24 hours.	Drug: Enoxaparin; Enoxaparin was administered at the commencement of PCI at a dose of 0.75 mg/kg
Active Comparator: 2 tirofiban and unfractionated heparin; Tirofiban was administered once the wire had crossed the lesion during PCI with a bolus dose of 25 µg/kg of bodyweight, followed by an infusion of 0.15 µg per kilogram per minute for 18 to 24 hours. UFH heparin was administered as a bolus of 70 U/kg and additional heparin was given to maintain the activated clotting time (ACT) at 250	Drug: Tirofiban; Drug: unfractionated heparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Thrombus generation as determined by Prothrombin fragment 1+2, D-dimer	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
A panel of platelet activation markers:P selectin, MAC-1, PMAs, factor V/Va,Platelet inhibition as assessed by whole blood aggregometry	10 minutes , 24 hours
Inflammatory biomarkers :CD40L,vWF and CRP	10 minutes,24 hours

Collaborators and Investigators

• Sponsor: The Prince Charles Hospital
• Collaborators: Sanofi; Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Darren L Walters, The Prince Charles Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: November 11, 2008
• First Submitted That Met QC Criteria: November 12, 2008
• First Posted (Estimate): November 13, 2008

Study Record Updates

• Last Update Posted (Estimate): March 24, 2010
• Last Update Submitted That Met QC Criteria: March 23, 2010
• Last Verified: November 1, 2008

More Information

Terms related to this study

• Keywords: enoxaparin; platelet inhibition; tirofiban; CD40L; percutaneous intervention; Mac-1; prothrombin fragment 1+2.
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Acute Coronary Syndrome; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Anticoagulants; Heparin; Tirofiban; Enoxaparin; Calcium heparin
• Other Study ID Numbers: EC2006