Clinical trial NCT00198588: Efficacy and Safety Study of Argatroban to Treat Heparin-Induced Thrombocytopenia
Official title: Open-Label Trial to Evaluate the Efficacy and Safety of the Use of Argatroban in Patients With Heparin-Induced Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heparin-Induced Thrombocytopenia
Keywords: heparin-induced thrombocytopenia
argatroban
cardiac surgery
acute coronary syndrome
thrombosis
amputation
anticoagulation
Lead sponsor: Ministry of Health, Labour and Welfare, Japan
Sponsor class: OTHER_GOV
Collaborators: name: Mitsubishi Tanabe Pharma Corporation
First posted: 2005-09-20
Enrollment: 8
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Death, new thrombosis, amputation
timeFrame: till 37 days
Secondary outcomes:
measure: Achievement of anticoagulation therapy
timeFrame: till 37 days
measure: Improvement of thrombocytopenia
timeFrame: till 37 days
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya Daini Red Cross Hospital
state: Aichi
city: Hakodate
country: Japan
facility: National Hospital Organization Hakodate National Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Hokkaido
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Hukuoka
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Kobe
country: Japan
facility: Kobe City General Hospital
state: Hyogo
city: Morioka
country: Japan
facility: Iwate Medical University Hospital
state: Iwate
city: Isehara
country: Japan
facility: Tokai University Hospital
state: Kanagawa
city: Tsu
country: Japan
facility: Mie University Hospital
state: Mie
city: Suita
country: Japan
facility: National Cardiovascular Center
state: Osaka
city: Fuchu
country: Japan
facility: Sakakibara Memorial Hospital
state: Tokyo
city: Iwakuni
country: Japan
facility: National Hospital Organization Iwakuni Clinical Center
state: Yamaguchi
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Kyoto
country: Japan
facility: Kyoto Second Red Cross Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Tokyo
country: Japan
facility: The University of Tokyo Hospital
city: Tokyo
country: Japan
facility: National Hospital Organization Tokyo Medical Center
city: Tokyo
country: Japan
facility: Keio University Hospital
Study officials:
affiliation: National Cerebral and Cardiovascular Center, Japan
name: Hitonobu TOMOIKE, MD, PhD
role: STUDY_CHAIR
References: