Open-Label, Randomised, Active Controlled, Multi-Centre Ph 3 Study to Evaluate the Safety and Efficacy of Danaparoid vs Argatroban in Acute HIT
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Aspen Global Incorporated
- Enrollment
- 7
- Locations
- 35
- Primary Endpoint
- Composite Efficacy Response
Study Overview
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)
Detailed Description
Objectives:
Primary:
To show that for the treatment of subjects with acute heparin-induced thrombocytopenia (HIT) danaparoid use is not inferior to argatroban in terms of efficacy. The primary efficacy endpoint (composite endpoint) is defined as treatment response at Day 44.
A subject will be considered a treatment responder, if none of the following events occur by Day 44:
- New or extended venous and/or arterial thrombosis, including gangrene/skin necrosis Note: 'thrombosis' denotes venous and/or arterial here and throughout the protocol
- All-cause mortality
- Unplanned amputation, including ischemic gut resection
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 2 Weeks to 100 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- •At the time of enrollmentsubjects are excluded from the study if any of the following criteria apply:
- •Premature infants (corrected age <37 weeks gestational age)
- •Subjects undergoing Extracorporeal Membrane Oxygenation (ECMO) treatment
- •Fibrinolytic therapy <24 hours before enrollment
- •Lumbar puncture or spinal/epidural catheter placement within the past 48 hours
- •Severe hepatic impairment (Child-Pugh Class C) Note: in patients with suspected/confirmed severe liver disease, Child-Pugh C stage of liver disease must be excluded before start of treatment. For calculating Child-Pugh score, laboratory parameters in the patient file on INR, prothrombin time, serum albumin and total bilirubin taken can be taken, if they have been obtained within the last 48 hours before randomization. In all other patients these parameters have to be measured before start of treatment to identify potential exclusion criteria.
- •Active bleeding
- •Subjects with the following conditions to be excluded if alternative antithrombotic treatments are available:
- •(i) Severe hemorrhagic diathesis, (ii) Traumatic damage to the central nervous system (iii) Brain, spinal or ophthalmologic surgery (iv) Active stomach/duodenal ulcers or active peptic ulcer unless this ulcer is the cause of the surgical procedure
- •An unexplained activated partial thromboplastin time (aPTT) > 2 x the normal range
- •A hemorrhagic cerebrovascular accident within the previous 3 months
- •Severe, uncontrolled hypertension defined as blood pressure >180/110 mmHg
- •Diabetic retinopathy
- •Acute bacterial endocarditis
- •Expectation of a long-term (> 3 weeks) hemodialysis requirement before the end of the acute treatment
- •Hypersensitivity to the active substances or to any of the excipients
- •Hypersensitivity to sulphite
- •Any investigational drug(s) use within 4 weeks preceding screening or anticipated use during the course of the study
- •Pregnant or breastfeeding woman
- •Use of intra-aortic balloon pump, or ventricular assist device
- •Use of any non-heparin anticoagulant treatment for suspected HIT for more than 48 hours before enrollment.
Arms & Interventions
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.
Intervention: Argatroban (Drug)
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.
Intervention: Danaparoid Sodium (Drug)
Outcomes
Primary Outcomes
Composite Efficacy Response
Time Frame: Day 44
Efficacy will be assessed by the number of subjects with suspected HIT who respond to treatment. A responder is defined as a subject who has not experienced any of the following from Day 1 to Day 44: 1. New or extended venous and/or arterial thrombosis, including gangrene/skin necrosis 2. All-cause mortality 3. Unplanned amputation, including ischemic gut resection Efficacy endpoints as defined above will be assessed by clinical exam with special attention to assessments for thromboses, gangrene, and skin necrosis. Clinically suspected thrombosis will be confirmed/ruled out by objective measures, e.g. compression ultrasound.
Secondary Outcomes
- Major Bleeding(Day 44)
- Consistent increases in platelet count(Days 14)
- Death due to TE or bleeding(Day 44)
- New or extended thrombosis(Day 44)
- Unplanned amputation(Day 44)
- All-cause mortality(Day 44)