Tirofiban and Enoxaparin in High Risk Coronary Intervention - Full Text View

Sponsors and Collaborators:	The Prince Charles Hospital Sanofi-Aventis Merck
Information provided by:	The Prince Charles Hospital
ClinicalTrials.gov Identifier:	NCT00790387

Purpose

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	Intervention	Phase
Acute Coronary Syndrome	Drug: Enoxaparin Drug: Tirofiban Drug: unfractionated heparin	Phase IV

MedlinePlus related topics: Blood Thinners

Drug Information available for: Heparin Enoxaparin Sodium CD40 Ligand Tirofiban Tirofiban hydrochloride Tirofiban hydrochloride monohydrate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacodynamics Study
Official Title:	High Bolus Dose Tirofiban and Enoxaparin Provides Reduced Thrombin Generation and Inflammatory Markers in Patients With High Risk Undergoing Percutaneous Intervention

Further study details as provided by The Prince Charles Hospital:

Primary Outcome Measures:

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

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 [ Time Frame: 10 minutes , 24 hours ] [ Designated as safety issue: Yes ]
Inflammatory biomarkers :CD40L,vWF and CRP [ Time Frame: 10 minutes,24 hours ] [ Designated as safety issue: No ]

Enrollment:	60
Study Start Date:	June 2004
Study Completion Date:	December 2006
Primary Completion Date:	December 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1 High dose tirofiban and enoxaparin: Experimental 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
2 tirofiban and unfractionated heparin: Active Comparator 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

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00790387

Locations

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

Sponsors and Collaborators

The Prince Charles Hospital

Sanofi-Aventis

Merck

Investigators

Principal Investigator:

Darren L Walters

The Prince Charles Hospital

More Information

Related Info This link exits the ClinicalTrials.gov site

Responsible Party:	The Prince Chalres Hospital ( Assoc Professor Darren Walters )
Study ID Numbers:	EC2006
Study First Received:	November 11, 2008
Last Updated:	November 13, 2008
ClinicalTrials.gov Identifier:	NCT00790387
Health Authority:	United States: Federal Government; Australia: Human Research Ethics Committee; Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by The Prince Charles Hospital:

enoxaparin
tirofiban
percutaneous intervention
platelet inhibition

CD40L
Mac-1
prothrombin fragment 1+2.

Study placed in the following topic categories:

Thrombin
Heart Diseases
Heparin, Low-Molecular-Weight
Tirofiban
Myocardial Ischemia
Acute Coronary Syndrome

Vascular Diseases
Ischemia
Heparin
Enoxaparin
Calcium heparin

Additional relevant MeSH terms:

Disease
Anticoagulants
Molecular Mechanisms of Pharmacological Action
Hematologic Agents
Fibrinolytic Agents
Cardiovascular Agents
Pharmacologic Actions

Fibrin Modulating Agents
Pathologic Processes
Syndrome
Therapeutic Uses
Cardiovascular Diseases
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009