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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)

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ClinicalTrials.gov Identifier: NCT03809481
Recruitment Status : Not yet recruiting
First Posted : January 18, 2019
Last Update Posted : January 24, 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

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)
Estimated Study Start Date : February 28, 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

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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

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: January 24, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Thrombocytopenia
Blood Platelet Disorders
Hematologic Diseases
Argatroban
Danaproid
Dermatan Sulfate
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Platelet Aggregation Inhibitors
Fibrinolytic Agents
Fibrin Modulating Agents