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

Heparin-Induced Thrombocytopenia Clinical Trial

Official title:

Open-Label Trial to Evaluate the Efficacy and Safety of the Use of Argatroban in Patients With Heparin-Induced Thrombocytopenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00198588
• Other study ID #: ARG-HIT-CVD
• Status: Completed
• Phase: Phase 3
• First received: September 12, 2005
• Last updated: November 11, 2008
• Start date: June 2005
• Est. completion date: September 2006

Study information

• Verified date: November 2008
• Source: Ministry of Health, Labour and Welfare, Japan
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: September 2006
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heparin-Induced Thrombocytopenia
• Thrombocytopenia
• Thrombocytosis

Intervention

Drug:
• argatroban
beginning dose: 0.7microgram/kg/H

Locations

Country	Name	City	State
Japan	Sakakibara Memorial Hospital	Fuchu	Tokyo
Japan	National Hospital Organization Hakodate National Hospital	Hakodate	Hokkaido
Japan	Tokai University Hospital	Isehara	Kanagawa
Japan	National Hospital Organization Iwakuni Clinical Center	Iwakuni	Yamaguchi
Japan	Kobe City General Hospital	Kobe	Hyogo
Japan	Kobe University Hospital	Kobe	Hyogo
Japan	Kurume University Hospital	Kurume	Hukuoka
Japan	Kyoto Second Red Cross Hospital	Kyoto
Japan	Kyoto University Hospital	Kyoto
Japan	Iwate Medical University Hospital	Morioka	Iwate
Japan	Nagoya Daini Red Cross Hospital	Nagoya	Aichi
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	National Hospital Organization Nagoya Medical Center	Nagoya	Aichi
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	National Cardiovascular Center	Suita	Osaka
Japan	Keio University Hospital	Tokyo
Japan	National Hospital Organization Tokyo Medical Center	Tokyo
Japan	The University of Tokyo Hospital	Tokyo
Japan	Mie University Hospital	Tsu	Mie
Japan	Yamaguchi University Hospital	Ube	Yamaguchi

Sponsors (2)

Lead Sponsor	Collaborator
Ministry of Health, Labour and Welfare, Japan	Mitsubishi Tanabe Pharma Corporation

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death, new thrombosis, amputation		till 37 days	Yes
Secondary	Achievement of anticoagulation therapy		till 37 days	Yes
Secondary	Improvement of thrombocytopenia		till 37 days	No