Tirofiban and Enoxaparin in High Risk Coronary Intervention

Sponsor

The Prince Charles Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00790387

Collaborator

Sanofi (Industry), Merck Sharp & Dohme LLC (Industry)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome	Drug: Enoxaparin Drug: Tirofiban Drug: unfractionated heparin	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2004

Actual Primary Completion Date :

Dec 1, 2005

Actual Study Completion Date :

Dec 1, 2006

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Thrombus generation as determined by Prothrombin fragment 1+2, D-dimer [24 hours]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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