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

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Angina, Unstable
• Intervention / Treatment: Drug: Heparin; Drug: Argatroban

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).

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium
• Germany
  • Bad Nauheim, Germany
  • Cologne, Germany
  • Dachau, Germany
  • Dueren, Germany
  • Frankfurt, Germany
  • Halle, Germany
  • Mainz, Germany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ARG250	Drug: Argatroban
EXPERIMENTAL: ARG300	Drug: Argatroban
EXPERIMENTAL: ARG350	Drug: Argatroban
PLACEBO_COMPARATOR: Heparin	Drug: Heparin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation

Publications and helpful links

General Publications

• Rossig L, Genth-Zotz S, Rau M, Heyndrickx GR, Schneider T, Gulba DC, Desaga M, Buerke M, Harder S, Zeiher AM; ARG-E04 study group. Argatroban for elective percutaneous coronary intervention: the ARG-E04 multi-center study. Int J Cardiol. 2011 Apr 14;148(2):214-9. doi: 10.1016/j.ijcard.2010.02.044. Epub 2010 Mar 11.

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Study Completion (ACTUAL): October 1, 2006

Study Registration Dates

• First Submitted: July 26, 2007
• First Submitted That Met QC Criteria: July 26, 2007
• First Posted (ESTIMATE): July 30, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): December 5, 2012
• Last Update Submitted That Met QC Criteria: November 6, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: PCI; Percutaneous coronary intervention; ACT; Argatroban; Direct thrombin inhibitor; Activated clotting time
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Coronary Disease; Chest Pain; Angina Pectoris; Coronary Artery Disease; Angina, Unstable; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Heparin; Argatroban
• Other Study ID Numbers: ARG-E04