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

NCT03809481 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: ERGCR-18-ORGHIT-001
• Study Type: interventional
• Target: 7
• Locations: 9 countries
• Sites: 35

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)

Conditions

Heparin-induced Thrombocytopenia

Outcome Measures

Primary Outcomes (1)

• Composite Efficacy Response

  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.

  Day 44

Secondary Outcomes (6)

• Consistent increases in platelet count

  Days 14

• Death due to TE or bleeding

  Day 44

• Major Bleeding

  Day 44

• New or extended thrombosis

  Day 44

• Unplanned amputation

  Day 44

Study Arms (2)

Danaparoid Sodium

EXPERIMENTAL

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

Argatroban

ACTIVE COMPARATOR

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

Interventions

Danaparoid Sodium DRUG

inhibits thrombin generation by indirect anti-Xa inhibition and direct inhibition of factor IX activation

Also known as: Orgaran

Danaparoid Sodium

Argatroban DRUG

Synthetic direct thrombin inhibitor

Argatroban

Eligibility Criteria

• Age: 2 Weeks - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Aspen Global Incorporated: lead

Study Sites (35)

Shands University of Florida

Gainesville, Florida, 32068, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77004, United States

Location

Clinical Center of the Republic of Srpska, Medical Intesnive Care Unit

Banja Luka, Republika Srpska, 78000, Bosnia and Herzegovina

Location

University Clinical Centre of the Republic of Srpska, Clinic for cardiology

Banja Luka, Bosnia and Herzegovina

Location

University Clinical Centre of the Republic of Srpska, Lung Clinic

Banja Luka, Bosnia and Herzegovina

Location

Clinical Center University of Sarajevo, Clinic for Heart, Blood Vessels and Rheumatic Diseases

Sarajevo, 71000, Bosnia and Herzegovina

Location

Clinical Center University of Sarajevo, Clinic for Lung Diseases

Sarajevo, 78000, Bosnia and Herzegovina

Location

Jewish General Hospital

Montreal, H3T 1E2, Canada

Location

CHU St Etienne; Avenue Albert Raimond

Saint-Priest-en-Jarez, Auvergne-Rhône-Alpes, 42270, France

Location

DIJON University Hospital

Dijon, Burgundy, 2100, France

Location

Centre Hospitalier Universitaire Amiens Picardie

Amiens, Somme, 80054, France

Location

Vivantes Klinikum im Friedrichhain Hämophiliezentrum, Gerinnungssprechstunde Landsberger Allee 49

Berlin, Berlin-Brandenburg, 10249, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH, Klinik für Herz-, Kinderherz- und Gefäßchirurgie Standort Gießen

Giesen, Lower Saxony, 35392, Germany

Location

Städtisches Klinkum Dresden

Dresden, Saxony, 1067, Germany

Location

Universitatstklinikum Halle (Saale), Medizinische Klinik III

Halle, Saxony-Anhalt, 06120, Germany

Location

University Hospital Greifswald Dpt. of Hematology

Greifswald, 17489, Germany

Location

Zentrum für Klinische Transfusionsmedizin

Tübingen, 72076, Germany

Location

Azienda Ospedaliero Universitaria S.Orsola-Malpighi - UO Angiologia e Malattie della Coagulazione

Bologna, Emilia-Romagna, 40138, Italy

Location

AOU Careggi, SOD Malattie Aterotrombotiche

Florence, Florence, 50134, Italy

Location

ASST Papa Giovanni XIII, Servizio di Immunoematologia e Medicina Trasfusionale

Bergamo, Lombardy, 24127, Italy

Location

Instituto Scientifico San Raffaele- Servizio Coagulazione e Centro Trombosi

Milan, 20132, Italy

Location

Centrum Medyczne HCP Sp. z o.o. Szpital im. Św. Jana Pawła II

Poznan, 61485, Poland

Location

Wojewódzki Szpital Zespolony im. L. Rydygiera

Torun, 87100, Poland

Location

First City Hospital N.A. E.E. Volosevich

Arkhangelsk, 163001, Russia

Location

Moscow City Hospital 67

Moscow, 123423, Russia

Location

Oncology Center

Omsk, 644013, Russia

Location

Regional Hospital after N.N Burdenko

Penza, 440026, Russia

Location

Clinical Hospital № 122 N. A. L.G. Sokolov

Saint Petersburg, 194291, Russia

Location

The Institute for Pulmonary Disease of Vojvodina, Pulmonary thromboembolism department

Novi Sad, Sremska Kamenica, 21204, Serbia

Location

Clinical Centre of Serbia, Clinic for Emergency Internal Medicine

Belgrade, 11000, Serbia

Location

Clinical centre of Serbia, Clinic for Pulmonology

Belgrade, 11000, Serbia

Location

Instiute of Cardiovascular Diseases "Dedinje"

Belgrade, 11040, Serbia

Location

MeSH Terms

Interventions

danaparoid; argatroban

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, randomized, active-controlled

Study Record Dates

• First Submitted: January 17, 2019
• First Posted: January 18, 2019
• Study Start: May 16, 2019
• Primary Completion: June 10, 2022
• Study Completion: June 10, 2022
• Last Updated: December 8, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

BO (5); DE (6); CA (1); IT (4); RU (5); US (5); FR (3); SE (4); PL (2)