Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

An Open-Label, Randomised, Active Controlled, Multi-Centre Phase 3 Study to Evaluate the Safety and Efficacy of Danaparoid vs Argatroban in Treatment of Subjects With Acute HIT (HITSOVA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03809481
Recruitment Status : Recruiting
First Posted : January 18, 2019
Last Update Posted : October 14, 2019
Sponsor:
Information provided by (Responsible Party):
Aspen Global Incorporated

Brief Summary:
An Open-Label, Randomised, Active Controlled, Multi-Centre Phase 3 Study to Evaluate the Safety and Efficacy of Danaparoid vs Argatroban in Treatment of Subjects with Acute HIT (HITSOVA study)

Condition or disease Intervention/treatment Phase
Heparin-induced Thrombocytopenia Drug: Danaparoid Sodium Drug: Argatroban Phase 3

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 508 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Open-label, randomized, active-controlled
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Open-Label, Randomised, Active Controlled, Multi-Centre Phase 3 Study to Evaluate the Safety and Efficacy of Danaparoid vs Argatroban in Treatment of Subjects With Acute HIT (HITSOVA Study)
Actual Study Start Date : May 16, 2019
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Argatroban

Arm Intervention/treatment
Experimental: Danaparoid Sodium
Subjects will receive danaparoid via IV infusion for at least 7 days then transition to a VKA. IV loading bolus injection of 2250 U, followed by 400 U/h for 4 hours, then 300 U/h for 4 hours, then a maintenance infusion of 150-200 U/h.
Drug: Danaparoid Sodium
inhibits thrombin generation by indirect anti-Xa inhibition and direct inhibition of factor IX activation
Other Name: Orgaran

Active Comparator: Argatroban
Subjects will receive argatroban 2 microgram/kg/min as a continuous infusion, titrated to an aPTT that is 1.5 to 3.0 x initial baseline value, but not exceeding 100 seconds.
Drug: Argatroban
Synthetic direct thrombin inhibitor




Primary Outcome Measures :
  1. Composite Efficacy Response [ Time Frame: Day 44 ]
    A subject will be considered a treatment responder if none of the following occur: New or extended thrombosis, all-cause mortality, unplanned amputation


Secondary Outcome Measures :
  1. Consistent increases in platelet count [ Time Frame: Days 3, 5, and 7 ]
    Consistent increases in platelets at days 3, 5, and 7

  2. Death due to TE or bleeding [ Time Frame: Day 44 ]
    Death due to TE or bleedin

  3. Major Bleeding [ Time Frame: Day 44 ]
    Fatal or non-fatal bleeding

  4. New or extended thrombosis [ Time Frame: Day 44 ]
    New of extended thrombosis, including gangrene/skin necrosis

  5. Unplanned amputation [ Time Frame: Day 44 ]
    Unplanned amputation, including ischemic gut resection

  6. All-cause mortality [ Time Frame: Day 44 ]
    All-cause mortality



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At the time of enrolment subjects are eligible to be included in the study only if all of the following criteria apply:

    1. Signed written informed consent by the subject, or if the subject is temporarily unable to do so, then consent will be sought from a family member, or a legally accepted representative as per local regulations
    2. Males or females aged ≥2 weeks
    3. Subjects with suspected HIT by 4Ts of >3 and with reduction of platelet count of ≥ 30% at either:

      1. Between Day 4 and 14 of the start of heparin exposure or
      2. At Day 1 of heparin exposure with pre-treatment with heparin within the last 30 days, with or without thrombosis.
    4. Have adequate renal function: Glomerular filtration rate ≥ 15 mL/min/1.73 m²
    5. Male participants:

      A male participant must agree to use contraception during the treatment period and for at least 5 days after the last dose of study intervention and refrain from donating sperm during this period.

    6. Female participants:

      A female participant is eligible to participate if 1 of the following conditions applies:

      1. Not a woman of childbearing potential OR
      2. A woman of childbearing potential who agrees to follow the contraceptive guidance during the treatment period and for at least 5 days corresponding to time needed to eliminate study intervention. (Subjects taking oral contraceptives or hormone replacement therapy must have a stable dose and regimen for ≥ 3 months prior to entry into the study.)
    7. Understanding/willingness by the subject or his/her legally accepted representative to participate in the clinical study and ability to comply with study procedures and the study visit schedule

Exclusion Criteria:

  • At the time of enrolment subjects are excluded from the study if any of the following criteria apply:

    1. Premature infants (corrected age <37 weeks gestational age)
    2. Expectation of cardiac surgery within the next 44 days
    3. Life expectancy clearly less than the 44 days
    4. Fibrinolytic therapy <24 hours before enrolment
    5. Lumbar puncture or spinal/epidural catheter placement within the past 48 hours
    6. Severe hepatic impairment (Child-Pugh Class C)
    7. Active bleeding
    8. Subjects with the following conditions to be excluded if alternative antithrombotic treatments are available:

      (i) Severe hemorrhagic diathesis, (ii) Damage to the central nervous system (iii) Brain, spinal or ophthalmologic surgery are to be excluded if alternative antithrombotic treatments are available.

      (iv) Active stomach/duodenal ulcers or active peptic ulcer unless this ulcer is the cause of the surgical procedure

    9. An unexplained activated partial thromboplastin time (aPTT) > 2 x the normal range
    10. A hemorrhagic cerebrovascular accident within the previous 3 months
    11. Severe, uncontrolled hypertension defined as blood pressure >180/110 mmHg
    12. Diabetic retinopathy
    13. Acute bacterial endocarditis
    14. Expectation of a long-term (> 3 weeks) hemodialysis requirement before the end of the acute treatment
    15. Hypersensitivity to the active substances or to any of the excipients
    16. Hypersensitivity to sulphite
    17. Any investigational drug(s) use within 4 weeks preceding Screening or anticipated use during the course of the study
    18. Pregnant or breastfeeding woman
    19. Use of intra-aortic balloon pump, or ventricular assist device

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03809481


Locations
Layout table for location information
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Thomas Ortel, MD    919-684-5350    Thomas.Ortel@duke.edu   
Principal Investigator: Thomas Ortel, MD         
Bosnia and Herzegovina
University Clinical Centre of the Republic of Srpska, Clinic for cardiology Recruiting
Banja Luka, Bosnia and Herzegovina
Contact: Sanja Stojkovic, MD    +387 65607836    drsanjastojkovic@gmail.com   
Principal Investigator: Sanja Stojkovic, MD         
University Clinical Centre of the Republic of Srpska, Lung Clinic Recruiting
Banja Luka, Bosnia and Herzegovina
Contact: Mirko Stanetic, Prof    +387 51343304    mirko.stanetic@kc-bl.com   
Principal Investigator: Mirko Stanetic, Prof         
Croatia
Clinical Hospital Centre Zagreb, Clinic for Internal Diseases, Department for Hematology Recruiting
Zagreb, Croatia, 10000
Contact: Silva Z Šalek, Prof    +3851 2388 672    szupanci@kbc-zagreb.hr   
Principal Investigator: Silva Z Šalek, Prof         
Czechia
University Hospital Brno, Dept. of Clinical Hematology Recruiting
Brno, Czechia, 62500
Contact: Miroslav Penka, MD    +420 532233941    penka.miroslav@fnbrno.cz   
Principal Investigator: Miroslav Penka, MD         
University Hospital Ostrava, Dept. of Hematooncology Recruiting
Ostrava, Czechia, 708 52
Contact: Jaromir Gumulec, MD    +420 597372296    jaromir.gumulec@fno.cz   
Principal Investigator: Jaromir Gumulec, MD         
Germany
Universitatstklinikum Halle (Saale), Medizinische Klinik III Recruiting
Halle (Saale), Saxony-Anhalt, Germany, 06120
Contact: Michel Noutsias, PHD MD    +49 345 557 3524    michel.noutsias@uk-halle.de   
Principal Investigator: Michel Noutsias, PHD MD         
University Hospital Greifswald Dpt. of Hematology Recruiting
Greifswald, Germany, 17489
Contact: Andreas Greinacher, Prof.    +49 383 486 5482    andreas.greinacher@med.uni-greifswald.de   
Hungary
DE OEC Thrombosis és Haemostasis Központ Recruiting
Debrecen, Hungary, 4032
Contact: Katalin Rázsó, MD    +36304873947    krazso@med.unideb.hu   
Principal Investigator: Katalin Rázsó, MD         
Italy
Instituto Scientifico San Raffaele- Servizio Coagulazione e Centro Trombosi Recruiting
Milano, Italy, 20132
Contact: Armando D'Angelo, Prof.    +39 02 26432228    dangelo.armando@hsr.it   
Principal Investigator: Armando D'Angelo, Prof.         
Poland
Centrum Medyczne HCP Sp. z o.o. Szpital im. Św. Jana Pawła II Recruiting
Poznań, Poland, 61485
Contact: Rafał Dankowski, MD    +48 606 812 742    rafal.dankowski@cmhcp.pl   
Principal Investigator: Rafał Dankowski, MD         
Wojewódzki Szpital Zespolony im. L. Rydygiera Recruiting
Toruń, Poland, 87100
Contact: Grzegorz Skonieczny, MD    +48 56 67 93 250    grzegorz.skonieczny@onet.eu   
Principal Investigator: Grzegorz Skonieczny, MD         
Invasive Cardiology Department Chair and Department of Cardiology Medical University in Lodz, Bieganski Hospital Recruiting
Łódź, Poland, 91347
Contact: Jan Zbigniew Peruga, MD    +48 42 251 6035    jzperuga@op.pl   
Principal Investigator: Jan Zbigniew Peruga, MD         
Serbia
Institute of Cardiovasklar Diseases of Vojvodina, Cardiac Surgery ICU Recruiting
Sremska Kamenica, Novi Sad, Serbia, 21204
Contact: Miodrag Golubovic, MD    +381 214805857    miodrag.golubovic@ikvbv.ns.ac.rs   
Principal Investigator: Miodrag Golubovic, MD         
Institute of Cardiovaskular Diseases of Vojvodina, Cardiology ICU Recruiting
Sremska Kamenica, Novi Sad, Serbia, 21204
Contact: Milovan Petrovic, MD    +381 214805777    milovan.petrovic@ikvbv.ns.ac.rs   
Principal Investigator: Milovan Petrovic, MD         
The Institute for Pulmonary Disease of Vojvodina, Pulmonary thromboembolism department Recruiting
Novi Sad, Sremska Kamenica, Serbia, 21204
Contact: Sandra Pekovic, MD    +381 214805175    sandra.pekovic@yahoo.com   
Principal Investigator: Sandra Pekovic, MD         
Clinical Centre of Serbia, Clinic for Emergency Internal Medicine Recruiting
Belgrade, Serbia, 11000
Contact: Branislav Stefanovic, Prof.    +381 113662333    bstefan@eunet.rs   
Principal Investigator: Branislav Stefanovic, Prof.         
Clinical centre of Serbia, Clinic for Pulmonology Recruiting
Belgrade, Serbia, 11000
Contact: Branislava Milenkovic, Prof.    +381 113663059    milenbra@gmail.com   
Principal Investigator: Branislava Milenkovic, Prof.         
Clinical Hospital Centre "Bezanijska kosa", Department of Cardiology Recruiting
Belgrade, Serbia, 11080
Contact: Sasa Hinic, MD    +381 113010754    hinicsasa@yahoo.com   
Principal Investigator: Sasa Hinic, MD         
Sponsors and Collaborators
Aspen Global Incorporated

Layout table for additonal information
Responsible Party: Aspen Global Incorporated
ClinicalTrials.gov Identifier: NCT03809481     History of Changes
Other Study ID Numbers: ERGCR-18-ORGHIT-001
First Posted: January 18, 2019    Key Record Dates
Last Update Posted: October 14, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Thrombocytopenia
Blood Platelet Disorders
Hematologic Diseases
Danaparoid
Argatroban
Dermatan Sulfate
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Platelet Aggregation Inhibitors
Fibrinolytic Agents
Fibrin Modulating Agents