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
- Interventions
- Drug: Human plasma derived antithrombinDrug: Placebo
- Registration Number
- NCT06096116
- Lead Sponsor
- Octapharma
- 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
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- 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
-
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, 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, 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- 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 Restoring heparin responsiveness 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 Outcome Measures
Name Time Method Amounts of further therapy for restoring heparin responsiveness 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
Change in activated clotting time (ACT) values 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
Change in antithrombin plasma levels 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
Change in heparin usage 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
FP unit use 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
Amounts of further antithrombin concentrate for maintaining heparin responsiveness 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)
Transfusion of allogenic blood products 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
Administration of coagulation factor concentrates 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
Administration of other haemostatic-relevant therapies 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
Postoperative chest tube drainage 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
Need for reoperation due to bleeding 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)
Cell saver volume 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
Adverse events 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
Serious adverse events From the start of IMP infusion until 28 days after IMP administration Incidence of serious adverse events
Survival status 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
Red Blood Cell count 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
White Blood Cell count 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
Haemoglobin levels 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
Haematocrit 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
Platelet count 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
Trial Locations
- Locations (18)
Stanford University School of Medicine
🇺🇸Stanford, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University Hospital Innsbruck
🇦🇹Innsbruck, Austria
Vienna General Hospital AKH, Medical University of Vienna
🇦🇹Vienna, Austria
Center of Cardiovascular and Transplant Surgery
🇨🇿Brno, Czechia
Institute for Clinical and Experimental Medicine
🇨🇿Prague, Czechia
CHU de Reims, Hôpital Robert Debré
🇫🇷Reims, France
CHU de Rennes
🇫🇷Rennes, France
Vilnius University Hospital Santaros Klinikos
🇱🇹Vilnius, Lithuania
Institute for Cardiovascular Diseases C.C. Iliescu
🇷🇴Bucharest, Romania
Royal Papworth Hospital
🇬🇧Cambridge, United Kingdom
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Atrium Health Wake Forest Baptist
🇺🇸Winston-Salem, North Carolina, United States
OU Health University of Oklahoma Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Hospital of Lithuanian university of Health sciences Kauno Klinikos
🇱🇹Kaunas, Lithuania
University Medical Centre Ljubljana
🇸🇮Ljubljana, Slovenia