Study on Safety and Effectiveness of Three Doses of Argatroban as Anticoagulant in Percutaneous Coronary Intervention (PCI)
Condition: Coronary Artery Disease; Angina, Unstable
MeSH terms: Coronary Artery Disease; Angina, Unstable
Intervention: Argatroban; Argatroban; Argatroban; Heparin
Intervention MeSH terms: Heparin; Argatroban
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 140.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Argatroban; Direct thrombin inhibitor; Percutaneous coronary intervention; Activated clotting time; PCI; ACT

Summary:

      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.
    

Eligibility criteria:

        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