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

Coronary Artery Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00508924
• Other study ID #: ARG-E04
• Status: Completed
• Phase: Phase 2
• First received: July 26, 2007
• Last updated: November 6, 2012
• Start date: August 2005
• Est. completion date: October 2006

Study information

• Verified date: November 2012
• Source: Mitsubishi Tanabe Pharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina, Unstable
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Argatroban

• Argatroban

• Argatroban

• Heparin

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma Corporation

Countries where clinical trial is conducted

Belgium,  Germany, 

References & Publications (1)

Rössig 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Activated Clotting Time (ACT) Value After the First Dosing of Study Treatment.		5 - 10 min after initial bolus	No
Primary	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	No