Open-Label, Randomised, Active Controlled, Multi-Centre Phase 3 Study to Evaluate Safety and Efficacy of Danaparoid vs Argatroban

• Status: Active, not recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

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)

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Aspen Global Incorporated
• Treatments: Argatroban; Danaparoid; Danaproid; Dermatan Sulfate

Criteria

At the time of enrollment 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 who is able to assess the nature, significance and scope of the clinical trial. If the subject is in emergency situation and temporarily incapable of consent, the consent of a legal representative or authorized representative will be waived if permitted under applicable local regulations/ethics committee recommendations. Consent must be obtained for further participation in the clinical trial as soon as this is possible and reasonable for the subject to do so to confirm understanding/willingness to participate in the clinical study and ability to comply with study procedures and the study visit schedule.

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: estimated glomerular filtration rate (eeGFR) ≥ 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: female participant is eligible to participate if 1 of the following conditions applies:

Not a woman of childbearing potential or A woman of childbearing potential who agrees to follow the contraceptive guidance during the treatment period and during the entire VKA use and for one month after cessation of its use. Subjects should continue with adequate contraception after the study end if they continue with VKA use. (Subjects taking oral contraceptives or hormone replacement therapy must have a stable dose and regimen for ≥ 3 months prior to entry into the study.)

Exclusion Criteria:

At the time of enrollmentsubjects are excluded from the study if any of the following criteria apply:

1. Premature infants (corrected age <37 weeks gestational age)

2. Subjects undergoing Extracorporeal Membrane Oxygenation (ECMO) treatment

3. Fibrinolytic therapy <24 hours before enrollment

4. Lumbar puncture or spinal/epidural catheter placement within the past 48 hours

5. 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.

6. Active bleeding

7. 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

8. An unexplained activated partial thromboplastin time (aPTT) > 2 x the normal range

9. A hemorrhagic cerebrovascular accident within the previous 3 months

10. Severe, uncontrolled hypertension defined as blood pressure >180/110 mmHg

11. Diabetic retinopathy

12. Acute bacterial endocarditis

13. Expectation of a long-term (> 3 weeks) hemodialysis requirement before the end of the acute treatment

14. Hypersensitivity to the active substances or to any of the excipients

15. Hypersensitivity to sulphite

16. Any investigational drug(s) use within 4 weeks preceding screening or anticipated use during the course of the study

17. Pregnant or breastfeeding woman

18. Use of intra-aortic balloon pump, or ventricular assist device

19. Use of any non-heparin anticoagulant treatment for suspected HIT for more than 48 hours before enrollment.