Clinical trial NCT00790387: Tirofiban and Enoxaparin in High Risk Coronary Intervention
Official title: High Bolus Dose Tirofiban and Enoxaparin Provides Reduced Thrombin Generation and Inflammatory Markers in Patients With High Risk Undergoing Percutaneous Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Keywords: enoxaparin
tirofiban
percutaneous intervention
platelet inhibition
CD40L
Mac-1
prothrombin fragment 1+2.
Lead sponsor: The Prince Charles Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Sanofi
name: Merck Sharp & Dohme LLC
First posted: 2008-11-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Thrombus generation as determined by Prothrombin fragment 1+2, D-dimer
timeFrame: 24 hours
Secondary outcomes:
measure: A panel of platelet activation markers:P selectin, MAC-1, PMAs, factor V/Va,Platelet inhibition as assessed by whole blood aggregometry
timeFrame: 10 minutes , 24 hours
measure: Inflammatory biomarkers :CD40L,vWF and CRP
timeFrame: 10 minutes,24 hours
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: The Prince Charles Hospital
state: Queensland
Study officials:
affiliation: The Prince Charles Hospital
name: Darren L Walters
role: PRINCIPAL_INVESTIGATOR
References: