Clinical Management of Argatroban in Patients With Heparin Induced Thrombocytopenia Type II

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00861692
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Duration (Months): 22
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to collect data on the clinical management of Argatroban in patients with suspected or confirmed heparin-induced thrombocytopenia Type II, with or without ongoing thrombosis who require parenteral antithrombotic therapy

Condition or Disease	Intervention/Treatment	Phase
Heparin-induced Thrombocytopenia Type II	Drug: argatroban	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multi-centre, Clinical Study to Collect Information on the Clinical Use of Argatroban in Patients With Heparin Induced Thrombocytopenia (HIT) Type II Who Require Parenteral Antithrombotic Therapy
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Argatroban	Drug: argatroban

Outcome Measures

Primary Outcome Measures

1. Composite of All-cause Death, Thrombosis (New and Extended) and Unplanned Amputation [During and 30 days after argatroban treatment]

2. All-cause Death [During and 30 days after argatroban treatment]

3. Death Related to Heparin-induced Thrombocytopenia (HIT) [During and 30 days after argatroban treatment]

4. Number of Patients With Thrombosis (New and Extended) [During and 30 days after argatroban treatment]

5. Number of Patients With Unplanned Amputation [During and 30 days after argatroban treatment]

6. Number of Patients With Major or Minor Bleeding [During and 30 days after argatroban treatment]

   Major bleeding is defined as i) overt and associated with a fall in the haemoglobin level 2 g/dl or more, ii) leads to transfusion of 2 units or more, iii) is retroperitoneal, iv) occurs into a major prosthetic joint, or v) in intracranial. Minor bleeding is defined as overt bleeding that does not meet the criteria of major bleeding.

7. Number of Patients With Platelet Count Recovery [Day 3]

   Platelet increase of ≥ 100G/L or 50%.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects aged >= 18 years

• Females of child bearing potential must have a negative urine pregnancy test prior to entry into the study

• Patients with suspected or confirmed heparin-induced thrombocytopenia Type II, with or without ongoing thrombosis who require parenteral anticoagulation

• Signed written informed consent by the subject, or if the subject is unable to do so, consent will be sought from their family member, or a trusted person nominated by the subject or the legal representative

Exclusion Criteria:

• Uncontrolled bleeding

• Severe hepatic impairment (Child-Pugh Class C)

• Hypersensitivity to argatroban or to any of the excipients (sorbitol and ethanol)

• Pregnancy (exclusion by routine urine test)

• Lactating woman

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Saint Etienne		France

Sponsors and Collaborators

• Mitsubishi Tanabe Pharma Corporation

Investigators

• Principal Investigator: Professor, Information at Mitsubishi Pharma Europe

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT00861692
• Other Study ID Numbers: ARG-E07
• First Posted: Mar 13, 2009
• Last Update Posted: Aug 1, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Mitsubishi Tanabe Pharma Corporation: Argatroban; heparin induced thrombocytopenia (HIT); direct thrombin inhibitor (DTI)
• Additional relevant MeSH terms: Thrombocytopenia; Argatroban

Study Results

Participant Flow

Arm/Group Title	Argatroban
Arm/Group Description	start with 1μg/kg/min infusion to be adjusted to aPTT 1.5-3.0 times the baseline values
Period Title: Overall Study
STARTED	20
COMPLETED	14
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Argatroban
Arm/Group Description	start with 1μg/kg/min infusion to be adjusted to aPTT 1.5-3.0 times the baseline values
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.7 (10.4)
Sex: Female, Male (Count of Participants)
Female	6 30%
Male	14 70%

Outcome Measures

1. Primary Outcome

Title	Composite of All-cause Death, Thrombosis (New and Extended) and Unplanned Amputation
Time Frame	During and 30 days after argatroban treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Argatroban
Arm/Group Description	start with 1μg/kg/min infusion to be adjusted to aPTT 1.5-3.0 times the baseline values
Measure Participants	20
Number [participants]	10 50%

2. Primary Outcome

Title	All-cause Death
Time Frame	During and 30 days after argatroban treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Argatroban
Arm/Group Description	start with 1μg/kg/min infusion to be adjusted to aPTT 1.5-3.0 times the baseline values
Measure Participants	20
Number [participants]	6 30%

3. Primary Outcome

Title	Death Related to Heparin-induced Thrombocytopenia (HIT)
Time Frame	During and 30 days after argatroban treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Argatroban
Arm/Group Description	start with 1μg/kg/min infusion to be adjusted to aPTT 1.5-3.0 times the baseline values
Measure Participants	20
Number [participants]	0 0%

4. Primary Outcome

Title	Number of Patients With Thrombosis (New and Extended)
Time Frame	During and 30 days after argatroban treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Argatroban
Arm/Group Description	start with 1μg/kg/min infusion to be adjusted to aPTT 1.5-3.0 times the baseline values
Measure Participants	20
Number [participants]	5 25%

5. Primary Outcome

Title	Number of Patients With Unplanned Amputation
Time Frame	During and 30 days after argatroban treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Argatroban
Arm/Group Description	start with 1μg/kg/min infusion to be adjusted to aPTT 1.5-3.0 times the baseline values
Measure Participants	20
Number [participants]	0 0%

6. Primary Outcome

Title	Number of Patients With Major or Minor Bleeding
Description	Major bleeding is defined as i) overt and associated with a fall in the haemoglobin level 2 g/dl or more, ii) leads to transfusion of 2 units or more, iii) is retroperitoneal, iv) occurs into a major prosthetic joint, or v) in intracranial. Minor bleeding is defined as overt bleeding that does not meet the criteria of major bleeding.
Time Frame	During and 30 days after argatroban treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Argatroban
Arm/Group Description	start with 1μg/kg/min infusion to be adjusted to aPTT 1.5-3.0 times the baseline values
Measure Participants	20
Number [participants]	4 20%

7. Primary Outcome

Title	Number of Patients With Platelet Count Recovery
Description	Platelet increase of ≥ 100G/L or 50%.
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

Data are missing in 3 patients.

Arm/Group Title	Argatroban
Arm/Group Description	start with 1μg/kg/min infusion to be adjusted to aPTT 1.5-3.0 times the baseline values
Measure Participants	17
Number [participants]	12 60%

Adverse Events

Arm/Group Title	Argatroban
Arm/Group Description	start with 1μg/kg/min infusion to be adjusted to aPTT 1.5-3.0 times the baseline values
All Cause Mortality
	Argatroban
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Argatroban
	Affected / at Risk (%)	# Events
Total	14/20 (70%)
Blood and lymphatic system disorders
DISSEMINATED INTRAVASCULAR COAGULATION	1/20 (5%)
THROMBOCYTOPENIA	1/20 (5%)
Cardiac disorders
ACUTE CORONARY SYNDROME	1/20 (5%)
CARDIAC ARREST	1/20 (5%)
CARDIAC FAILURE CONGESTIVE	1/20 (5%)
CARDIOGENIC SHOCK	1/20 (5%)
MYOCARDIAL RUPTURE	1/20 (5%)
Gastrointestinal disorders
PERITONITIS	2/20 (10%)
COLITIS	1/20 (5%)
HAEMATEMESIS	1/20 (5%)
PNEUMATOSIS INTESTINALIS	1/20 (5%)
RECTAL HAEMORRHAGE	1/20 (5%)
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION	1/20 (5%)
MULTI-ORGAN FAILURE	1/20 (5%)
Infections and infestations
SEPSIS	3/20 (15%)
SEPTIC SHOCK	1/20 (5%)
Injury, poisoning and procedural complications
MEDICATION ERROR	1/20 (5%)
Renal and urinary disorders
ACUTE PRERENAL FAILURE	1/20 (5%)
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME	2/20 (10%)
HYPOXIA	1/20 (5%)
LUNG DISORDER	1/20 (5%)
PULMONARY EMBOLISM	1/20 (5%)
RESPIRATORY FAILURE	1/20 (5%)
Skin and subcutaneous tissue disorders
RASH ERYTHEMATOUS	1/20 (5%)
Vascular disorders
BLUE TOE SYNDROME	1/20 (5%)
FEMORAL ARTERY EMBOLISM	1/20 (5%)
HAEMORRHAGE	1/20 (5%)
JUGULAR VEIN THROMBOSIS	1/20 (5%)
PELVIC VENOUS THROMBOSIS	1/20 (5%)
PERIPHERAL ISCHAEMIA	1/20 (5%)
Other (Not Including Serious) Adverse Events
	Argatroban
	Affected / at Risk (%)	# Events
Total	17/20 (85%)
Blood and lymphatic system disorders
Anaemia	7/20 (35%)
Coagulopathy	1/20 (5%)
Leukopenia	1/20 (5%)
Pancytopenia	1/20 (5%)
Thrombocytopenia	1/20 (5%)
Cardiac disorders
Atrial Fibrillation	3/20 (15%)
Bradycardia	2/20 (10%)
Mitral Valve Incompetence	1/20 (5%)
Tachycardia	1/20 (5%)
Gastrointestinal disorders
Abdominal Pain	2/20 (10%)
Colonic Polyp	1/20 (5%)
Constipation	5/20 (25%)
Diarrhoea	1/20 (5%)
Haemorrhoids	1/20 (5%)
Ileus	1/20 (5%)
Impaired Gastric Emptying	1/20 (5%)
Melaena	1/20 (5%)
Mouth Haemorrhage	1/20 (5%)
Nausea	2/20 (10%)
Rectal Haemorrhage	1/20 (5%)
Vomiting	2/20 (10%)
General disorders
Asthenia	2/20 (10%)
Chest Pain	1/20 (5%)
Generalised Oedema	1/20 (5%)
Hyperthermia	2/20 (10%)
Inflammation	2/20 (10%)
Injection Site Inflammation	1/20 (5%)
Malaise	1/20 (5%)
Oedema Peripheral	2/20 (10%)
Pain	4/20 (20%)
Puncture Site Haemorrhage	1/20 (5%)
Pyrexia	4/20 (20%)
Hepatobiliary disorders
Cholestasis	2/20 (10%)
Hepatic Function Abnormal	1/20 (5%)
Jaundice	1/20 (5%)
Jaundice Cholestatic	1/20 (5%)
Liver Disorder	1/20 (5%)
Immune system disorders
Hypogammaglobulinaemia	1/20 (5%)
Infections and infestations
Device Related Infection	4/20 (20%)
Escherichia Urinary Tract Infection	2/20 (10%)
Fungal Infection	1/20 (5%)
Fungal Sepsis	1/20 (5%)
Gastroenteritis	1/20 (5%)
Infection	1/20 (5%)
Lung Infection	1/20 (5%)
Pneumonia	2/20 (10%)
Postoperative Wound Infection	1/20 (5%)
Sepsis	1/20 (5%)
Sinusitis	1/20 (5%)
Urinary Tract Infection	1/20 (5%)
Injury, poisoning and procedural complications
Haemodialysis Complication	1/20 (5%)
Incision Site Pain	1/20 (5%)
Overdose	3/20 (15%)
Post Procedural Haemorrhage	1/20 (5%)
Postoperative Wound Complication	1/20 (5%)
Procedural Pain	1/20 (5%)
Investigations
Alpha Globulin Increased	1/20 (5%)
Blood Pressure Decreased	1/20 (5%)
Coagulation Time Prolonged	2/20 (10%)
Cytomegalovirus Test Positive	1/20 (5%)
Globulins Decreased	1/20 (5%)
Glomerular Filtration Rate Increased	1/20 (5%)
Haemoglobin Decreased	2/20 (10%)
International Normalised Ratio Increased	2/20 (10%)
Pulmonary Function Test Decreased	2/20 (10%)
Transaminases Increased	1/20 (5%)
Weight Decreased	2/20 (10%)
Metabolism and nutrition disorders
Dehydration	1/20 (5%)
Diabetes Mellitus	1/20 (5%)
Folate Deficiency	2/20 (10%)
Hypernatraemia	1/20 (5%)
Hypoalbuminaemia	2/20 (10%)
Hypocalcaemia	2/20 (10%)
Hypokalaemia	3/20 (15%)
Hypomagnesaemia	1/20 (5%)
Hypophosphataemia	2/20 (10%)
Hypovolaemia	1/20 (5%)
Vitamin D Deficiency	1/20 (5%)
Musculoskeletal and connective tissue disorders
Pain In Extremity	2/20 (10%)
Nervous system disorders
Altered State Of Consciousness	1/20 (5%)
Depressed Level Of Consciousness	1/20 (5%)
Monoparesis	1/20 (5%)
Paraesthesia	1/20 (5%)
Polyneuropathy	1/20 (5%)
Somnolence	1/20 (5%)
Psychiatric disorders
Anxiety	1/20 (5%)
Confusional State	3/20 (15%)
Depression	3/20 (15%)
Insomnia	3/20 (15%)
Sleep Disorder	1/20 (5%)
Renal and urinary disorders
Calculus Bladder	1/20 (5%)
Dysuria	1/20 (5%)
Haematuria	1/20 (5%)
Renal Failure Acute	1/20 (5%)
Renal Impairment	1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Acute Lung Injury	1/20 (5%)
Atelectasis	1/20 (5%)
Bronchial Obstruction	1/20 (5%)
Dyspnoea	2/20 (10%)
Haemoptysis	1/20 (5%)
Hypercapnia	1/20 (5%)
Hypocapnia	1/20 (5%)
Hypoventilation	1/20 (5%)
Hypoxia	2/20 (10%)
Lung Disorder	1/20 (5%)
Pleural Effusion	2/20 (10%)
Pneumothorax	1/20 (5%)
Pulmonary Oedema	1/20 (5%)
Respiratory Failure	2/20 (10%)
Respiratory Tract Congestion	1/20 (5%)
Skin and subcutaneous tissue disorders
Rash	1/20 (5%)
Rash Macular	1/20 (5%)
Skin Dystrophy	1/20 (5%)
Vascular disorders
Aortic Arteriosclerosis	1/20 (5%)
Deep Vein Thrombosis	1/20 (5%)
Haemodynamic Instability	3/20 (15%)
Hypertension	3/20 (15%)
Hypotension	5/20 (25%)
Venous Thrombosis	1/20 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.