Study on Safety and Effectiveness of Three Doses of Argatroban as Anticoagulant in Percutaneous Coronary Intervention (PCI)

Study Overview
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Brief Summary
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This is a phase II multi-centre study in 140 patients undergoing elective PCI to obtain the information on dose-response of argatroban in pharmacodynamic markers and to assess the anticoagulation, safety and efficacy of argatroban in reference to unfractionated heparin, in combination with dual antiplatelet therapy.

Detailed Description
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This is a phase II multi-centre study in Europe in patients with stable coronary artery disease or troponin negative unstable angina undergoing elective PCI, to obtain the information on the safety and effects on various pharmacodynamic markers, of three doses of argatroban in combination with clopidogrel and aspirin, and to assess the results of argatroban and unfractionated heparin, both used in combination with clopidogrel and aspirin, on clinical outcomes, adequacy of anticoagulation, various pharmacodynamic markers (approximately 35 patients per group).

Official Title
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A Randomised, Open, Parallel-group, Multicentre Study to Examine the Safety and Effectiveness of Three Doses of Argatroban as Anticoagulant in Combination With Clopidogrel and Aspirin in Patients Undergoing Elective Percutaneous Coronary Intervention in Comparison With Unfractionated Heparin, Clopidogrel and Aspirin

Conditions
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Coronary Artery Disease, Angina, Unstable

Intervention / Treatment
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* Drug: Argatroban
* Drug: Argatroban
* Drug: Argatroban
* Drug: Heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female (women of child bearing potential must have a negative pregnancy test prior to entry into the study) Aged over 18 years Diagnosis of stable coronary artery disease (CAD) or unstable angina (troponin negative, i.e. within the normal range for the study site) with low to moderate anatomic risk and a requirement for elective percutaneous coronary angioplasty or stent insertion with an approved device in one or more de novo-treated or re-stenotic lesions in native vessels Signed written informed consent Exclusion Criteria: Any condition which, in the investigator's opinion, contraindicates the use of argatroban, heparin or clopidogrel or endangers the patient if he/she participated in this study. Known cirrhosis, hepatitis, clinically significant hepatic disorder, or history of hepatic disorder. Hepatic disorder is defined as having levels of liver function tests (bilirubin, Aspartate Aminotransferase (Serum Glutamate Oxaloacetate Transaminase)(AST (SGOT)), Alanine Aminotransferase (Serum Glutamate Pyruvate Transaminase)(ALT (SGPT)) greater than 3.0 times above the upper limit of the normal range of local laboratory. Patients not currently taking aspirin Renal insufficiency, defined as serum creatinine greater than 2.0 mg/dL (greater than 177mmol/L) Platelets less than 125,000/ml If already taking any form of heparin prior to study enrolment, Activated Partial Thromboplastin Time(aPTT) equal or greater than 35 sec or ACT greater than 160 sec Use of low molecular heparin (LMWH) during 12 h prior to PCI If taking oral anticoagulant medication prior to study enrolment, International Normalised Ratio(INR) greater than 1.2 Q wave MI with cardiogenic shock or thrombolytic therapy within 72 h of study dosing Use of Glycoprotein IIb / IIIa(GPIIb/IIIa) inhibitors within prior 3 weeks Documented coagulation disorder or bleeding diathesis Lumbar puncture within the past 2 weeks History of previous cerebral aneurysm, haemorrhagic stroke, or thrombotic stroke within the past 6 months Active, uncontrolled peptic ulcer disease or any gastrointestinal bleeding or genitourinary bleeding within 3 months prior to study enrolment Major surgery, serious trauma, puncture of non-compressible vessel, or biopsy of parenchymal organ within prior 2 months Planned staged procedure, planned rotational atherectomy, directional coronary atherectomy, brachytherapy, or thrombectomy catheters Planned surgical intervention other than study procedure within next 7 days Presence of greater than 50% stenosis of unprotected left main coronary artery Severe peripheral vascular disease, precluding femoral access History of vasculitis Uncontrolled hypertension defined as greater than 180/120 mmHg Pregnancy (exclusion by routine urine test) Lactating woman Woman of children bearing age who are or were not using accepted contraceptive methods Participation in other clinical trials of investigational products within 3 months prior to study enrolment Terminally ill patients with a life expectancy of < 3 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARG250<br> | Drug: Argatroban<br> <br> |
| Experimental: ARG300<br> | Drug: Argatroban<br> <br> |
| Experimental: ARG350<br> | Drug: Argatroban<br> <br> |
| Placebo Comparator: Heparin<br> | Drug: Heparin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activated Clotting Time (ACT) Value After the First Dosing of Study Treatment. |  | 5 - 10 min after initial bolus | 
| Composite and Each of Death, Myocardial Infarction, and Urgent Revascularisation at Day 30, and Major Bleeding Events During Hospital Stay. | Composite end point (a): all cause death, myocardial infarction and urgent revascularization at Day30 Composite end point (b): all cause death, myocardial infarction and urgent revascularization at Day30 as well as major bleeding events during hospital stay | 30 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Argatroban, Direct thrombin inhibitor, Percutaneous coronary intervention, Activated clotting time, PCI, ACT