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

This study has been completed.
Sponsor:
Information provided by:
Mitsubishi Tanabe Pharma Corporation
ClinicalTrials.gov Identifier:
NCT00508924
First received: July 26, 2007
Last updated: November 6, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Angina, Unstable
Drug: Argatroban
Drug: Heparin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Mitsubishi Tanabe Pharma Corporation:

Primary Outcome Measures:
  • Activated Clotting Time (ACT) Value After the First Dosing of Study Treatment. [ Time Frame: 5 - 10 min after initial bolus ] [ Designated as safety issue: No ]
  • Composite and Each of Death, Myocardial Infarction, and Urgent Revascularisation at Day 30, and Major Bleeding Events During Hospital Stay. [ Time Frame: 30 Days ] [ Designated as safety issue: No ]

    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



Enrollment: 140
Study Start Date: August 2005
Study Completion Date: October 2006
Arms Assigned Interventions
Experimental: ARG250 Drug: Argatroban
Experimental: ARG300 Drug: Argatroban
Experimental: ARG350 Drug: Argatroban
Placebo Comparator: Heparin Drug: Heparin

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00508924

Locations
Belgium
Aalst, Belgium
Germany
Bad Nauheim, Germany
Cologne, Germany
Dachau, Germany
Dueren, Germany
Frankfurt, Germany
Halle, Germany
Mainz, Germany
Sponsors and Collaborators
Mitsubishi Tanabe Pharma Corporation
Investigators
Principal Investigator: Professor Information at Mitsubishi Pharma Europe
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00508924     History of Changes
Other Study ID Numbers: ARG-E04
Study First Received: July 26, 2007
Results First Received: November 6, 2012
Last Updated: November 6, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Mitsubishi Tanabe Pharma Corporation:
Argatroban
Direct thrombin inhibitor
Percutaneous coronary intervention
Activated clotting time
PCI
ACT

Additional relevant MeSH terms:
Angina, Unstable
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Angina Pectoris
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Arteriosclerosis
Arterial Occlusive Diseases
Calcium heparin
Argatroban
Anticoagulants
Heparin
Antithrombins
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014