Tirofiban and Enoxaparin in High Risk Coronary Intervention

• ClinicalTrials.gov Identifier: NCT00790387
• Recruitment Status: Completed
• First Posted: November 13, 2008
• Last Update Posted: March 24, 2010
• Sponsor: The Prince Charles Hospital
• Collaborators: Sanofi; Merck Sharp & Dohme Corp.
• Information provided by: The Prince Charles Hospital

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 (Clinical Trial)
• 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: June 2004
• Actual Primary Completion Date: December 2005
• Actual Study Completion Date: December 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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Australia, Queensland

The Prince Charles Hospital

Brisbane, Queensland, Australia, 4032

Sponsors and Collaborators

The Prince Charles Hospital

Sanofi

Merck Sharp & Dohme Corp.

Investigators

• Principal Investigator: Darren L Walters; The Prince Charles Hospital

More Information

• Responsible Party: Assoc Professor Darren Walters, The Prince Chalres Hospital
• ClinicalTrials.gov Identifier: NCT00790387
• Other Study ID Numbers: EC2006
• First Posted: November 13, 2008
• Last Update Posted: March 24, 2010
• Last Verified: November 2008

Keywords provided by The Prince Charles Hospital:

enoxaparin; tirofiban; percutaneous intervention; platelet inhibition; CD40L; Mac-1; prothrombin fragment 1+2.

Additional relevant MeSH terms:

Acute Coronary Syndrome; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Heparin; Enoxaparin; Calcium heparin; Tirofiban; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors