Clinical trial • Phase III • Cardiology
Antithrombin III (human) for Acquired antithrombin III deficiency | Heparin resistance
Phase III trial of Antithrombin III (human) for Acquired antithrombin III deficiency | Heparin resistance.
Overview
- Trial Therapeutic Area
- Cardiology
- Trial Disease
- Acquired antithrombin III deficiency | Heparin resistance
- Trial Stage
- Phase III
- Drug Modality
- Peptide/protein/enzyme | Small molecule
Key dates
- Initial CTIS Submission Date
- 15-04-2024
- First CTIS Authorization Date
- 01-08-2024
Trial design
Randomised, placebo (normal saline bolus) comparator arm; active arms: atenativ single bolus 15 iu/kg bodyweight and atenativ single bolus 30 iu/kg bodyweight (administration: single iv bolus prior to cpb).-controlled Phase III trial across 15 sites in Austria, Czechia, France and others.
- Randomised
- Yes
- Comparator
- Placebo (normal saline bolus) comparator arm; Active arms: Atenativ single bolus 15 IU/kg bodyweight and Atenativ single bolus 30 IU/kg bodyweight (administration: single IV bolus prior to CPB).
- Target Sample Size
- 89
- Trial Duration For Participant
- 7
Eligibility
Recruits 89 Vulnerable population selected. Informed consent requirement: "Freely given written or electronic informed consent". Trial enrols adults only (Patients ≥18 and ≤85 years of age). No specific assent procedures or additional vulnerable-consent handling details are provided in the available documents..
- Pregnancy Exclusion
- In female patients of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile), a pre-existing negative pregnancy test within 14 days prior to surgery
- Vulnerable Population
- Vulnerable population selected. Informed consent requirement: "Freely given written or electronic informed consent". Trial enrols adults only (Patients ≥18 and ≤85 years of age). No specific assent procedures or additional vulnerable-consent handling details are provided in the available documents.
Inclusion criteria
- {"criterion_text":"- Planned cardiac surgery with CPB\n- Heparin-resistant patients: pre-CPB Hemochron ACT less than 480 seconds in the measurement performed between 2 and 5 minutes following intravenous administration of 500 U/kg BW UFH\n- Patients ≥18 and ≤85 years of age\n- Freely given written or electronic informed consent\n- In female patients of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile), a pre-existing negative pregnancy test within 14 days prior to surgery"}
Exclusion criteria
- {"criterion_text":"- Receiving or have received one or more of the following medications within the specified time frames prior to the start of the surgery: a) vitamin K antagonists (within 3 days) b) direct oral anticoagulants (within 2 days) c) thienopyridines (ticlopidine within 14 days, prasugrel within 7 days, or clopidogrel within 5 days), unless platelet function is satisfactory d) ticagrelor (within 5 days), unless platelet function is satisfactory e) glycoprotein IIb/IIIa antagonist (within 24 hours)\n- Pre-existing coagulopathy, a history of bleeding problems or a laboratory-diagnosed bleeding disorder (e.g., von Willebrand disease, platelet disorder)\n- Renal insufficiency, defined as serum creatinine level >2.0 mg/dL\n- Thrombocytosis, defined as platelet count >400,000 per µL\n- Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ, i.e., human albumin, sodium chloride, acetyl tryptophan and caprylic acid\n- History of anaphylactic reaction(s) to blood or blood components\n- Refusal to receive transfusion of blood or blood-derived products\n- Current participation in another interventional clinical trial with an investigational medicinal product (IMP) or previous participation in the current trial\n- Treatment with any IMP within 30 days prior to screening visit"}
Endpoints
Primary endpoints
- {"endpoint_text":"- The primary efficacy endpoint is the percentage of patients in each group in whom no further therapy containing antithrombin (i.e., FP or other antithrombin concentrates) is needed for restoring pre-CPB heparin responsiveness after administration of Atenativ or placebo, and for maintaining it during CPB.","definition_or_measurement_approach":"Measured as the percentage of patients per treatment group who do not require any additional antithrombin-containing therapy (frozen plasma or antithrombin concentrates) to restore pre-CPB heparin responsiveness after administration of study drug (Atenativ or placebo) and to maintain heparin responsiveness during cardiopulmonary bypass (CPB)."}
Secondary endpoints
- {"endpoint_text":"- The comparison between the amounts of further therapy containing antithrombin (i.e., FP or antithrombin concentrates) needed for restoring pre-CPB heparin responsiveness after administration of Atenativ or placebo, and for maintaining it during CPB\n- The comparison between the change in ACT values following infusion of each of the Atenativ doses and placebo\n- The comparison between the change in antithrombin plasma levels following infusion of each of the Atenativ doses and placebo\n- The comparison between heparin usage following the infusion of each of the Atenativ doses and placebo\n- The comparison between the number of units of FP transfused for reasons other than restoring or maintaining heparin responsiveness, both intraoperatively (from the start of Atenativ or placebo infusion until the start of CPB, during CPB, and from the end of CPB until the end of surgery) and postoperatively (from the end of surgery until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first), as well as cumulatively\n- The comparison between postoperative use of antithrombin concentrates for reasons other than restoring heparin responsiveness (from the end of surgery until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first)\n- The comparison between transfusion of other allogeneic blood products (i.e., red blood cells [RBCs], platelets, cryoprecipitate, whole blood, albumin, other transfusion), both intraoperatively and postoperatively, as well as cumulatively\n- The comparison between administration of coagulation factor concentrates (fibrinogen concentrate, prothrombin complex concentrate (PCC), factor XIII concentrate, recombinant activated factor VII, other therapy), both intraoperatively and postoperatively, as well as cumulatively\n- The comparison between administration of other haemostatic-relevant therapies (i.e., tranexamic acid, aminocaproic acid, protamine, other therapies), both intraoperatively and postoperatively, as well as cumulatively\n- The comparison between postoperative chest tube drainage volume at 24 hours after the start of Atenativ or placebo infusion, and the comparison between total chest tube drainage volume until discharge or 7 days after surgery, whichever comes first\n- Comparison of the need for reoperation for bleeding, including description of the cause of bleeding (surgical vs. non-surgical)\n- The comparison between cell saver volume until the end of surgery\n- Incidence of AEs in the three study groups\n- Standard haematological parameters (i.e., RBC count, white blood cell count, haemoglobin levels, haematocrit, and platelet count) following Atenativ or placebo infusion, after the end of CPB, at the end of surgery, and at 24 hours after the start of Atenativ or placebo infusion\n- Survival status in the different treatment groups.\n- The comparison between the amounts of further therapy containing antithrombin (i.e., FP or antithrombin concentrates) needed for restoring heparin responsiveness from the end of CPB until 24 hours after start of Atenativ or placebo infusion and from the end of CPB until discharge or 7 days postoperatively, whichever comes first\n- Comparison of the length of ICU stay between treatment groups.","definition_or_measurement_approach":"Secondary endpoints comprise comparisons between treatment groups for amounts of additional antithrombin therapy, changes in ACT and antithrombin plasma levels, heparin usage, transfusions (FP and other allogeneic products), use of coagulation factor concentrates and haemostatic therapies, chest tube drainage volumes (24-hour and total until discharge or 7 days), need for reoperation for bleeding (surgical vs non-surgical), cell saver volume, incidence of adverse events, standard haematological parameters at defined perioperative timepoints, survival status, and ICU length of stay. Several endpoints include time windows defined as intraoperative, postoperative up to 24 hours, and up to discharge or 7 days post-surgery, whichever comes first."}
Recruitment
- Planned Sample Size
- 89
- Recruitment Window Months
- 26
- Consent Approach
- Informed consent must be "Freely given written or electronic informed consent". Only adults (Patients ≥18 and ≤85 years) are eligible. Subject information and informed consent forms (SIS/ICF) are provided; multiple language versions are available (documents include versions in English, French, Czech, Polish, Lithuanian, Romanian, Slovenian, Spanish and other local language ICFs as listed).
Geography
- Total Number Of Sites
- 15
- Total Number Of Participants
- 53
Austria
- Earliest CTIS Part Ii Submission Date
- 05-08-2024
- Latest Decision Or Authorization Date
- 18-12-2025
- Processing Time Days
- 500
- Number Of Sites
- 2
- Number Of Participants
- 7
Sites
- Site Name
- Medizinische Universitaet Innsbruck
- Department Name
- Department of Anaesthesia and Critical Care Medicine
- Principal Investigator Name
- Simon Mathis
- Principal Investigator Email
- simon.mathis@tirol-kliniken.at
- Contact Person Name
- Simon Mathis
- Contact Person Email
- simon.mathis@tirol-kliniken.at
- Site Name
- Medical University of Vienna, AKH
- Department Name
- Department of Anaesthesia, Intensive Care Medicine and Pain Medicine
- Principal Investigator Name
- Edda Tschernko
- Principal Investigator Email
- edda.tschernko@meduniwien.ac.at
- Contact Person Name
- Edda Tschernko
- Contact Person Email
- edda.tschernko@meduniwien.ac.at
Czechia
- Earliest CTIS Part Ii Submission Date
- 05-08-2024
- Latest Decision Or Authorization Date
- 17-12-2025
- Processing Time Days
- 499
- Number Of Sites
- 2
- Number Of Participants
- 13
Sites
- Site Name
- Centrum kardiovaskulární a transplantační chirurgie Brno
- Department Name
- Úsek anesteziologie, resuscitace a intenzivní medicíny
- Principal Investigator Name
- Olga Hrazdilova
- Principal Investigator Email
- Olga.Hrazdilova@cktch.cz
- Contact Person Name
- Olga Hrazdilova
- Contact Person Email
- Olga.Hrazdilova@cktch.cz
- Site Name
- Institute For Clinical And Experimental Medicine
- Department Name
- Klinika anesteziologie a resuscitace
- Principal Investigator Name
- Milan Ročeň
- Principal Investigator Email
- milan.rocen@ikem.cz
- Contact Person Name
- Milan Ročeň
- Contact Person Email
- milan.rocen@ikem.cz
France
- Earliest CTIS Part Ii Submission Date
- 06-08-2024
- Latest Decision Or Authorization Date
- 17-12-2025
- Processing Time Days
- 498
- Number Of Sites
- 2
- Number Of Participants
- 1
Sites
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- Cardiothoracic Intensive Care Unit
- Principal Investigator Name
- Alexandre Mansour
- Principal Investigator Email
- alexandre.mansour@chu-rennes.fr
- Contact Person Name
- Alexandre Mansour
- Contact Person Email
- alexandre.mansour@chu-rennes.fr
- Site Name
- Centre Hospitalier Universitaire Reims
- Department Name
- Anesthesie-Reanimation
- Principal Investigator Name
- Ayoub El Amri
- Principal Investigator Email
- ael-amri@chu-reims.fr
- Contact Person Name
- Ayoub El Amri
- Contact Person Email
- ael-amri@chu-reims.fr
Lithuania
- Earliest CTIS Part Ii Submission Date
- 05-08-2024
- Latest Decision Or Authorization Date
- 17-12-2025
- Processing Time Days
- 499
- Number Of Sites
- 2
- Number Of Participants
- 5
Sites
- Site Name
- Vilniaus Universiteto Ligonine Santaros Klinikos Vsi
- Department Name
- Širdies chirurgijos anesteziologijos ir intensyviosios terapijos skyriaus
- Principal Investigator Name
- Robertas Stasys Samalavičius
- Principal Investigator Email
- Robertas.Samalavicius@santa.lt
- Contact Person Name
- Robertas Stasys Samalavičius
- Contact Person Email
- Robertas.Samalavicius@santa.lt
- Site Name
- Lietuvos sveikatos mokslu universiteto ligonine Kauno klinikos
- Department Name
- Širdies chirurgijos anesteziologijos ir intensyviosios terapijos skyriaus
- Principal Investigator Name
- Tadas Lenkutis
- Principal Investigator Email
- tadas.lenkutis@kaunoklinikos.lt
- Contact Person Name
- Tadas Lenkutis
- Contact Person Email
- tadas.lenkutis@kaunoklinikos.lt
Romania
- Earliest CTIS Part Ii Submission Date
- 06-08-2024
- Latest Decision Or Authorization Date
- 19-12-2025
- Processing Time Days
- 500
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Institutul De Urgenta Pentru Boli Cardiovasculare Prof. Dr. C. C. Iliescu
- Department Name
- Cardiac anesthesia and intensive care medicine II
- Principal Investigator Name
- Daniela Carmen Filipescu
- Principal Investigator Email
- ibcardio@gmail.com
- Contact Person Name
- Daniela Carmen Filipescu
- Contact Person Email
- ibcardio@gmail.com
Slovenia
- Earliest CTIS Part Ii Submission Date
- 01-08-2024
- Latest Decision Or Authorization Date
- 19-12-2025
- Processing Time Days
- 505
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- University Medical Center Ljubljana
- Department Name
- Clinical Department of Anesthesiology and Surgical Intensive Care
- Principal Investigator Name
- Maja ŠoštariČ
- Principal Investigator Email
- maja.sostaric@kclj.si
- Contact Person Name
- Maja Šoštarič
- Contact Person Email
- maja.sostaric@kclj.si
Spain
- Earliest CTIS Part Ii Submission Date
- 27-03-2026
- Latest Decision Or Authorization Date
- 27-03-2026
- Processing Time Days
- 0
- Number Of Sites
- 3
- Number Of Participants
- 13
Sites
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- Anesthesiology
- Principal Investigator Name
- Maria Azuzena Pajares Moncho
- Principal Investigator Email
- pajares_maz@gva.es
- Contact Person Name
- Maria Azuzena Pajares Moncho
- Contact Person Email
- pajares_maz@gva.es
- Site Name
- Hospital Clinico San Carlos
- Department Name
- Anesthesiology
- Principal Investigator Name
- Ruben Sanchez Martin
- Principal Investigator Email
- rsanchezmartin@salud.madrid.org
- Contact Person Name
- Ruben Sanchez Martin
- Contact Person Email
- rsanchezmartin@salud.madrid.org
- Site Name
- Hospital Clinico Universitario De Valencia
- Department Name
- Anesthesiology
- Principal Investigator Name
- Rafael José Badenes Quiles
- Principal Investigator Email
- rafaelbadenes@gmail.com
- Contact Person Name
- Rafael José Badenes Quiles
- Contact Person Email
- rafaelbadenes@gmail.com
Poland
- Earliest CTIS Part Ii Submission Date
- 09-04-2026
- Latest Decision Or Authorization Date
- 09-04-2026
- Processing Time Days
- 0
- Number Of Sites
- 2
- Number Of Participants
- 6
Sites
- Site Name
- Uniwersytecki Szpital Kliniczny W Poznaniu
- Department Name
- Oddział Kardiochirurgii i Transplantologii
- Principal Investigator Name
- Bartłomiej Perek
- Principal Investigator Email
- bperek@ump.edu.pl
- Contact Person Name
- Bartłomiej Perek
- Contact Person Email
- bperek@ump.edu.pl
- Site Name
- Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
- Department Name
- Kliniki Anestezjologii I Intensywnej Terapii
- Principal Investigator Name
- Waldemar Gozdzik
- Principal Investigator Email
- waldemar.gozdzik@umw.edu.pl
- Contact Person Name
- Waldemar Gozdzik
- Contact Person Email
- waldemar.gozdzik@umw.edu.pl
Sponsor
Primary sponsor
- Full Name
- Octapharma AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- Metronomia Clinical Research GmbH
- Responsibilities
- 10,6,7
- Name
- Clinigen Clinical Supplies Management GmbH
- Responsibilities
- 14
- Name
- Optimapharm d.o.o.
- Responsibilities
- 1,12,13,2,5,8
Third parties
- {"country":"Germany","full_name":"Octapharma Dessau GmbH","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
- {"country":"Bulgaria","full_name":"Comac Medical Ltd.","duties_or_roles":"1,12,13,2,5","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"Clinigen Clinical Supplies Management GmbH","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"GBA Central Lab Services GmbH","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"GxP Brain GmbH","duties_or_roles":"3","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"Metronomia Clinical Research GmbH","duties_or_roles":"10,6,7","organisation_type":"Pharmaceutical company"}
- {"country":"Croatia","full_name":"Optimapharm d.o.o.","duties_or_roles":"1,12,13,2,5,8","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Atenativ (ANTITHROMBIN III HUMAN) - multiple marketed presentations (e.g., Atenativ 50 IU/ml; Atenativ 500 I.E.; Atenativ 1000 I.E.)
- Active Substance
- Antithrombin III (human)
- Modality
- Peptide/protein/enzyme
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Marketing-authorised product in multiple countries (marketing authorisation numbers present in product dictionary info)
- Starting Dose
- 15 IU/kg (single IV bolus)
- Dose Levels
- 15 IU/kg; 30 IU/kg
- Frequency
- Single bolus
- Maximum Dose
- 60 IU/kg (max daily total as listed in product data)
- Dose Escalation Increase
- 15 IU/kg -> 30 IU/kg
- Investigational Product Name
- Isotone Natriumchloridlösung 0,9 % Braun (placebo; sodium chloride 0.9%)
- Active Substance
- Sodium chloride
- Modality
- Small molecule
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Marketing-authorised product (marketing authorisation data present)
- Starting Dose
- Normal saline bolus (ml/kg dosing; trial placebo arm receives normal saline bolus)
- Dose Levels
- Placebo (single bolus)
- Frequency
- Single bolus
- Maximum Dose
- 1.2 ml/kg (max daily as listed in product data)
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