A clinical trial looking at the effectiveness and safety of a human plasma-derived antithrombin called Atenativ, for patients who are resistant to heparin (a blood thinner) and are undergoing cardiac surgery with cardiopulmonary bypass

Approved 15/10/2024, Yorkshire & The Humber - Sheffield Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, United Kingdom; +44 (0)2071048139, (0)2071048135, (0)207 104 8210; sheffield.rec@hra.nhs.uk), ref: 24/YH/0183

The percentage of patients in each group in whom no further therapy containing antithrombin (i.e., frozen plasma (FP) or other antithrombin concentrates) is needed for restoring pre-CPB heparin responsiveness after administration of Atenativ or placebo, and for maintaining it until the completion of the cardiopulmonary bypass (CPB). The CPB period includes any additional CPB time if a return to CPB is needed before protamine administration but excludes any additional CPB time required after protamine administration.

The following secondary outcome measures are assessed at various intraoperative and postoperative timepoints between initial heparin administration and 28 days following IMP infusion:
1. 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. The comparison between the change in ACT values following infusion of each of the Atenativ doses and placebo
3. The comparison between the change in antithrombin plasma levels following infusion of each of the Atenativ doses and placebo
4. The comparison between heparin usage following the infusion of each of the Atenativ doses and placebo
5. 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. 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. The comparison between transfusion of other allogeneic blood products (e.g., red blood cells [RBCs], platelets, cryoprecipitate), 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. The comparison between administration of coagulation factor concentrates such as fibrinogen concentrate, prothrombin complex concentrate (PCC), factor XIII concentrate and recombinant activated factor VII, both intraoperatively and postoperatively
9. The comparison between administration of other haemostatic-relevant therapies (e.g., tranexamic acid, protamine), 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 This document is an unpublished preview, not for official use
10. 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. Comparison of the need for reoperation for bleeding, including description of the cause of bleeding (surgical vs. non-surgical)
12. The comparison between cell saver volume until the end of surgery
13. Incidence of AEs in the three study groups
14. 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
15. Survival status in the different treatment groups
16. 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
17. Comparison of the length of ICU stay between treatment groups