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NCT Number: NCT06096116

Phase 3 Study on the Efficacy and Safety of Human Plasma Derived Antithrombin (Atenativ) in Heparin-Resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass

The primary objective of this study is to evaluate the efficacy of two different doses of Atenativ, versus placebo, in restoring and maintaining heparin responsiveness in adult patients undergoing cardiac surgery necessitating cardiopulmonary bypass (CPB)

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Key information

Conditions

Acquired Antithrombin Deficiency Antithrombin III Deficiency Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Blood Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Thrombophilia

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University Hospital Innsbruck, Innsbruck, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Planned cardiac surgery with CPB
  • Heparin-resistant patients (pre-CPB Hemochron ACT less than 480 s in the measurement taken between 2-5 minutes following intravenous administration of 500 U/kg UFH)
  • Patients between 18 and 85 years of age, inclusive
  • Freely given written or electronic informed consent
  • In female patients of childbearing potential, a pre-existing negative pregnancy test within 14 days prior to surgery

Exclusion criteria

  • Receiving, or have received within the timeframes specified, one or more of the following medications prior to the start of surgery:
  • vitamin K antagonists (within 3 days)
  • direct oral anticoagulants (within 2 days)
  • thienopyridines (ticlopidine within 14 days, prasugrel within 7 days, or clopidogrel within 5 days), unless platelet function is satisfactory according to local standard of care assessment
  • ticagrelor (within 5 days), unless platelet function is satisfactory according to local standard of care assessment
  • glycoprotein IIb/IIIa antagonist (within 24 hours)
  • Pre-existing coagulopathy, a history of bleeding problems, or a laboratory-diagnosed bleeding disorder (e.g., von Willebrand disease, platelet disorder)
  • Renal insufficiency, defined as serum creatinine level >2.0 mg/dL
  • Thrombocytosis, defined as platelet count >400,000 per μL
  • Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ, i.e., human albumin, sodium chloride, acetyl tryptophan, caprylic acid
  • History of anaphylactic reaction(s) to blood or blood components
  • Refusal to receive transfusion of blood or blood-derived products
  • Current participation in another interventional clinical trial or previous participation in the current trial
  • Treatment with any IMP within 30 days prior to screening visit

Treatment and study plan

Human plasma derived antithrombin

Drug

A solvent/detergent and heat-treated antithrombin concentrate derived from human plasma

Placebo

Drug

Half of the patients in the placebo group will be randomised to receive a volume of placebo corresponding to the low dose of Atenativ and the other half to receive a volume of placebo corresponding to a high dose of Atenativ

Primary outcomes

  1. Restoring heparin responsiveness

    Time frame: During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed)

    The percentage of patients in each group in whom no further therapy containing antithrombin (i.e. frozen plasma or other antithrombin concentrates) is needed for restoring pre-CPB heparin responsiveness after administration of Atenativ or placebo, and for maintaining it during CPB

Secondary outcomes

  1. Amounts of further therapy for restoring heparin responsiveness

    Time frame: During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed)

    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

  2. Change in activated clotting time (ACT) values

    Time frame: Within 5 minutes following intravenous administration of 500 U/kg unfractionated heparin (UFH) and between 2-10 minutes after IMP infusion

    The comparison between the change in ACT values following infusion of each of the Atenativ doses and placebo

  3. Change in antithrombin plasma levels

    Time frame: Within 10 minutes before IMP infusion and between 2 and 10 minutes after IMP infusion, within 10 minutes after the end of CPB, at the end of surgery, and at 24 hours after the start of IMP infusion

    The comparison between the change in antithrombin plasma levels following infusion of each of the Atenativ doses and placebo

  4. Change in heparin usage

    Time frame: From end of IMP infusion to the end of surgery

    The comparison between heparin usage following the infusion of each of the Atenativ doses and infusion of placebo

  5. FP unit use

    Time frame: From the start of IMP infusion until 24 hours following IMP infusion, and until discharge or 7 days after surgery, whichever comes first

    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

  6. Amounts of further antithrombin concentrate for maintaining heparin responsiveness

    Time frame: From placement of the final suture or staple until 24 hours following IMP infusion, to discharge or 7 days after surgery, whichever comes first

    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)

  7. Transfusion of allogenic blood products

    Time frame: From the start of IMP infusion until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first

    The comparison between transfusion of other allogeneic blood products (e.g., red blood cells [RBCs], platelets, cryoprecipitate, whole blood, albumin, other transfusion), 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

  8. Administration of coagulation factor concentrates

    Time frame: From the start of IMP infusion until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first

    The comparison between administration of coagulation factor concentrates (fibrinogen concentrate, factor XIII concentrate, recombinant activated factor VII, other therapy)", 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

  9. Administration of other haemostatic-relevant therapies

    Time frame: From the start of IMP infusion until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first

    The comparison between administration of other haemostatic-relevant therapies (i.e., tranexamic acid, aminocaproic acid, protamine, other therapies), 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

  10. Postoperative chest tube drainage

    Time frame: From the start of IMP infusion to 24 hours after infusion and until discharge or 7 days after surgery, whichever comes first

    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

  11. Need for reoperation due to bleeding

    Time frame: 24 hours after the start of IMP infusion

    Comparison of the need for reoperation for bleeding, including description of the cause of bleeding (surgical vs. non-surgical)

  12. Cell saver volume

    Time frame: During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed)

    The comparison between cell saver volume until the end of surgery

  13. Adverse events

    Time frame: From the start of IMP infusion until hospital discharge or 7 days after IMP administration, whichever comes first

    Incidence of adverse events, including all related and non-related, non-serious adverse events

  14. Serious adverse events

    Time frame: From the start of IMP infusion until 28 days after IMP administration

    Incidence of serious adverse events

  15. Survival status

    Time frame: At hospital discharge or 7 days after IMP administration (whichever comes first) and at 28 days (+ 4 days) after IMP administration

    Number of patients surviving in all three cohorts

  16. Red Blood Cell count

    Time frame: Within 10 minutes before IMP infusion, between 2-10 minutes after IMP infusion, within 10 minutes after the end of CPB, at the end of surgery, and at 24 hours after infusion

    Standard haematological parameter

  17. White Blood Cell count

    Time frame: Within 10 minutes before IMP infusion, between 2-10 minutes after IMP infusion, within 10 minutes after the end of CPB, at the end of surgery, and at 24 hours after infusion

    Standard haematological parameter

  18. Haemoglobin levels

    Time frame: Within 10 minutes before IMP infusion, between 2-10 minutes after IMP infusion, within 10 minutes after the end of CPB, at the end of surgery, and at 24 hours after infusion

    Standard haematological parameter

  19. Haematocrit

    Time frame: Within 10 minutes before IMP infusion, between 2-10 minutes after IMP infusion, within 10 minutes after weaning from CPB, at the end of surgery, and at 24 hours after infusion

    Standard haematological parameter

  20. Platelet count

    Time frame: Within 10 minutes before IMP infusion, between 2-10 minutes after IMP infusion, within 10 minutes after weaning from CPB, at the end of surgery, and at 24 hours after infusion

    Standard haematological parameter

Study contacts

Contact information is provided by the study sponsor or research team.

Cristina Solomon, MD

CONTACT

[email protected]

+41 79 585 90 42

Sponsors and collaborators

Lead sponsor

Octapharma

Industry

Registry information

Official study title

Phase 3, Double-blind, Placebo-controlled, Multicentre Study on the Efficacy and Safety of Human Plasma Derived Antithrombin (Atenativ) in Heparin-Resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass

Important dates

Study start
2024
Primary completion
2028
Study completion
2028
First posted
Oct 23, 2023
Registry last updated
May 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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