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
- Conditions
- Acquired Antithrombin Deficiency (Heparin Resistance)
- Interventions
- Drug: Human plasma derived antithrombinDrug: Placebo
- Registration Number
- 2023-507560-39-00
- Lead Sponsor
- Octapharma AG
- Brief Summary
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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 58
Planned cardiac surgery with CPB
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
Patients ≥18 and ≤85 years of age
Freely given written or electronic informed consent
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
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)
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
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
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 with an investigational medicinal product (IMP) or previous participation in the current trial
Treatment with any IMP within 30 days prior to screening visit
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description High-dose Atenativ Human plasma derived antithrombin - Placebo Placebo Patients will receive a saline bolus dose Low-dose Atenativ Human plasma derived antithrombin -
- Primary Outcome Measures
Name Time Method 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. 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.
- Secondary Outcome Measures
Name Time Method 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 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
The comparison between the change in ACT values following infusion of each of the Atenativ doses and placebo The comparison between the change in ACT values following infusion of each of the Atenativ doses and placebo
The comparison between the change in antithrombin plasma levels following infusion of each of the Atenativ doses and placebo The comparison between the change in antithrombin plasma levels following infusion of each of the Atenativ doses and placebo
The comparison between heparin usage following the infusion of each of the Atenativ doses and placebo The comparison between heparin usage following the infusion of each of the Atenativ doses and placebo
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 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
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) 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)
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 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
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 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
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 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
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 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
Comparison of the need for reoperation for bleeding, including description of the cause of bleeding (surgical vs. non-surgical) Comparison of the need for reoperation for bleeding, including description of the cause of bleeding (surgical vs. non-surgical)
The comparison between cell saver volume until the end of surgery The comparison between cell saver volume until the end of surgery
Incidence of AEs in the three study groups Incidence of AEs in the three study groups
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 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
Survival status in the different treatment groups. Survival status in the different treatment groups.
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 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
Comparison of the length of ICU stay between treatment groups. Comparison of the length of ICU stay between treatment groups.
Trial Locations
- Locations (10)
Medizinische Universitaet Innsbruck
🇦🇹Innsbruck, Austria
Medical University of Vienna, AKH
🇦🇹Vienna, Austria
Institutul De Urgenta Pentru Boli Cardiovasculare Prof. Dr. C. C. Iliescu
🇷🇴Bucharest, Romania
University Medical Center Ljubljana
🇸🇮Ljubljana, Slovenia
Centre Hospitalier Universitaire De Rennes
🇫🇷Rennes, France
Centre Hospitalier Universitaire Reims
🇫🇷Reims Cedex, France
Institute For Clinical And Experimental Medicine
🇨🇿Prague, Czechia
Centrum kardiovaskulární a transplantační chirurgie Brno
🇨🇿Brno, Czechia
Lietuvos sveikatos mokslu universiteto ligonine Kauno klinikos
🇱🇹Kaunas, Lithuania
Vilniaus Universiteto Ligonine Santaros Klinikos Vsi
🇱🇹Vilnius, Lithuania
Medizinische Universitaet Innsbruck🇦🇹Innsbruck, AustriaSimon MathisSite contact004351250422400simon.mathis@tirol-kliniken.at