Tirofiban and Enoxaparin in High Risk Coronary Intervention

This study has been completed.
Sponsor:
Collaborators:
Sanofi
Merck Sharp & Dohme Corp.
Information provided by:
The Prince Charles Hospital
ClinicalTrials.gov Identifier:
NCT00790387
First received: November 11, 2008
Last updated: March 23, 2010
Last verified: November 2008
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


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
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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Darren L Walters The Prince Charles Hospital
  More Information

No publications provided

Responsible Party: Assoc Professor Darren Walters, The Prince Chalres Hospital
ClinicalTrials.gov Identifier: NCT00790387     History of Changes
Other Study ID Numbers: EC2006
Study First Received: November 11, 2008
Last Updated: March 23, 2010
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.

Additional relevant MeSH terms:
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Calcium heparin
Heparin
Enoxaparin
Tirofiban
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014