Efficacy and Safety Study of Argatroban to Treat Heparin-Induced Thrombocytopenia

This study has been completed.
Sponsor:
Collaborator:
Mitsubishi Tanabe Pharma Corporation
Information provided by:
Ministry of Health, Labour and Welfare, Japan
ClinicalTrials.gov Identifier:
NCT00198588
First received: September 12, 2005
Last updated: November 11, 2008
Last verified: November 2008
  Purpose

The purpose of the study is to evaluate efficacy and safety of argatroban in the patients with heparin-induced thrombocytopenia (HIT)/ HIT and thrombosis syndrome (HITTS). This multi-center trial covers mainly the patients with cardiovascular diseases. Subjects are included in the trial when they are clinically diagnosed of HIT/HITTS. Initial dose of argatroban is 0.7μg/kg/min, which is about one-third of the approved dose in the US. The reason of the lower initial dose is that the approved dose of argatroban in Japan (for the treatment of ischemic stroke) is about 0.7μg/kg/min and safety of higher doses of the drug are not confirmed. A sub-study of pharmacokinetics is simultaneously conducted to reveal the relationship among the dose, aPTT, and blood drug concentration.


Condition Intervention Phase
Heparin-Induced Thrombocytopenia
Drug: argatroban
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-Label Trial to Evaluate the Efficacy and Safety of the Use of Argatroban in Patients With Heparin-Induced Thrombocytopenia

Resource links provided by NLM:


Further study details as provided by Ministry of Health, Labour and Welfare, Japan:

Primary Outcome Measures:
  • Death, new thrombosis, amputation [ Time Frame: till 37 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Achievement of anticoagulation therapy [ Time Frame: till 37 days ] [ Designated as safety issue: Yes ]
  • Improvement of thrombocytopenia [ Time Frame: till 37 days ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: June 2005
Study Completion Date: September 2006
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: argatroban
    beginning dose: 0.7microgram/kg/H
  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males of non-pregnant females >=20 and <=80 years of age
  2. Those with the diagnosis of HIT or HITTS made by the following diagnostic criteria, or those who have positive results of HIT antibody

    • diagnostic criteria of HIT
    • a fall in platelet count to less than 100,000/μL or a 50% decrease in platelets after the initiation of heparin therapy with no apparent explanation other than HIT
    • diagnostic criteria of HITTS

      • those who met the diagnosis criteria of HIT
      • presence of an arterial or venous thrombosis documented by appropriate imaging technique (ultrasound, angiography etc.) or supported by clinical evidence such as a myocardial infarction, stroke, pulmonary embolism, or other clinical indications of vascular occlusion(absence of pulse, cold, cyanotic extremities, etc.)
    • patients with history of HIT/HITTS with positive test results (HIT antibody or platelet function test) could be enrolled without present thrombocytopenia
  3. patients willing and able to give informed consent

Exclusion Criteria:

  1. any condition which in the investigator's opinion, contraindicated the use of argatroban or endangered the patient if he or she participated in this trial
  2. clinically significant or uncontrolled endocrine, renal, pulmonary, gastrointestinal, or psychiatric disorder of sufficient severity that the investigator deemed antithrombotic therapy with argatroban to be contraindicated
  3. unexplained aPTT>200% of control at baseline
  4. documented coagulation disorder or unexplained bleeding diathesis unrelated to HIT
  5. lumbar puncture within the past 7 days
  6. known clinical site of bleeding. Patients with a known site of clinical bleeding could be enrolled if the investigator deemed the risk of continued thrombosis outweighed the potential bleeding risk
  7. serious liver disfunction
  8. females of known or suspected pregnancy
  9. breast feeding females
  10. participation in other clinical drug trials within the past 30 days
  11. history of hypersensitivity to argatroban
  12. concomitant use of cimetidine
  13. previous participation in this trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00198588

Locations
Japan
National Hospital Organization Nagoya Medical Center
Nagoya, Aichi, Japan, 4600001
Nagoya University Hospital
Nagoya, Aichi, Japan, 4668560
Nagoya Daini Red Cross Hospital
Nagoya, Aichi, Japan, 4668650
National Hospital Organization Hakodate National Hospital
Hakodate, Hokkaido, Japan, 0418512
National Hospital Organization Hokkaido Cancer Center
Sapporo, Hokkaido, Japan, 0030804
Kurume University Hospital
Kurume, Hukuoka, Japan, 8300011
Kobe City General Hospital
Kobe, Hyogo, Japan, 6500046
Kobe University Hospital
Kobe, Hyogo, Japan, 6500017
Iwate Medical University Hospital
Morioka, Iwate, Japan, 0208505
Tokai University Hospital
Isehara, Kanagawa, Japan, 2591193
Mie University Hospital
Tsu, Mie, Japan, 5148507
National Cardiovascular Center
Suita, Osaka, Japan, 5658565
Sakakibara Memorial Hospital
Fuchu, Tokyo, Japan, 1830003
National Hospital Organization Iwakuni Clinical Center
Iwakuni, Yamaguchi, Japan, 7408510
Yamaguchi University Hospital
Ube, Yamaguchi, Japan, 7558505
Kyoto University Hospital
Kyoto, Japan, 6068507
Kyoto Second Red Cross Hospital
Kyoto, Japan, 6028026
National Hospital Organization Tokyo Medical Center
Tokyo, Japan, 1528902
The University of Tokyo Hospital
Tokyo, Japan, 1138655
Keio University Hospital
Tokyo, Japan, 1608582
Sponsors and Collaborators
Ministry of Health, Labour and Welfare, Japan
Mitsubishi Tanabe Pharma Corporation
Investigators
Study Chair: Hitonobu TOMOIKE, MD, PhD National Cerebral and Cardiovascular Center
  More Information

No publications provided

Responsible Party: Haruko Yamamoto, National Cardiovascular Center
ClinicalTrials.gov Identifier: NCT00198588     History of Changes
Other Study ID Numbers: ARG-HIT-CVD
Study First Received: September 12, 2005
Last Updated: November 11, 2008
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Ministry of Health, Labour and Welfare, Japan:
heparin-induced thrombocytopenia
argatroban
cardiac surgery
acute coronary syndrome
thrombosis
amputation
anticoagulation

Additional relevant MeSH terms:
Thrombocytopenia
Blood Platelet Disorders
Hematologic Diseases
Argatroban
Heparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014