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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

Phase 3
Recruiting
Conditions
Acquired Antithrombin Deficiency (Heparin Resistance)
Interventions
Drug: Human plasma derived antithrombin
Drug: 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
Inclusion Criteria

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

Exclusion Criteria

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
GroupInterventionDescription
High-dose AtenativHuman plasma derived antithrombin-
PlaceboPlaceboPatients will receive a saline bolus dose
Low-dose AtenativHuman plasma derived antithrombin-
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
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, Austria
Simon Mathis
Site contact
004351250422400
simon.mathis@tirol-kliniken.at
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