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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low-dose Atenativ | Experimental | Patients will receive a single bolus of 30 international units (IU)/kg body weight (BW) Atenativ. |
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| High-dose Atenativ | Experimental | Patients will receive a single bolus of 60 international units (IU)/kg body weight (BW) Atenativ. |
|
| Placebo | Placebo Comparator | Patients will receive a saline bolus dose |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Human plasma derived antithrombin | Drug | A solvent/detergent and heat-treated antithrombin concentrate derived from human plasma |
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| Measure | Description | Time Frame |
|---|---|---|
| Restoring heparin responsiveness | 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 | During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed) |
| Measure | Description | Time Frame |
|---|---|---|
| Amounts of further therapy for restoring heparin responsiveness | 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 | During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed) |
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Inclusion Criteria:
Exclusion Criteria:
Receiving, or have received within the timeframes specified, one or more of the following medications prior to the start of surgery:
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
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Cristina Solomon, MD | Contact | +41 79 585 90 42 | Cristina.Solomon@octapharma.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University School of Medicine | Recruiting | Stanford | California | 94305-5101 | United States | |
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Triple (Participant, Care Provider, Outcomes Assessor) The patients, care provider administering IMP, and outcomes assessors will be blinded from treatment allocations. Delegated study personnel preparing the IMP will be unblinded.
| 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 |
|
| Change in activated clotting time (ACT) values | The comparison between the change in ACT values following infusion of each of the Atenativ doses and placebo | Within 5 minutes following intravenous administration of 500 U/kg unfractionated heparin (UFH) and between 2-10 minutes after IMP infusion |
| Change in antithrombin plasma levels | The comparison between the change in antithrombin plasma levels following infusion of each of the Atenativ doses and placebo | 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 |
| Change in heparin usage | The comparison between heparin usage following the infusion of each of the Atenativ doses and infusion of placebo | From end of IMP infusion to the end of surgery |
| FP unit use | 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 | From the start of IMP infusion until 24 hours following IMP infusion, and until discharge or 7 days after surgery, whichever comes first |
| Amounts of further antithrombin concentrate for maintaining heparin responsiveness | 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) | From placement of the final suture or staple until 24 hours following IMP infusion, to discharge or 7 days after surgery, whichever comes first |
| Transfusion of allogenic blood products | 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 | 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 |
| Administration of coagulation factor concentrates | 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 | 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 |
| Administration of other haemostatic-relevant therapies | 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 | 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 |
| Postoperative chest tube drainage | 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 | From the start of IMP infusion to 24 hours after infusion and until discharge or 7 days after surgery, whichever comes first |
| Need for reoperation due to bleeding | Comparison of the need for reoperation for bleeding, including description of the cause of bleeding (surgical vs. non-surgical) | 24 hours after the start of IMP infusion |
| Cell saver volume | The comparison between cell saver volume until the end of surgery | During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed) |
| Adverse events | Incidence of adverse events, including all related and non-related, non-serious adverse events | From the start of IMP infusion until hospital discharge or 7 days after IMP administration, whichever comes first |
| Serious adverse events | Incidence of serious adverse events | From the start of IMP infusion until 28 days after IMP administration |
| Survival status | Number of patients surviving in all three cohorts | At hospital discharge or 7 days after IMP administration (whichever comes first) and at 28 days (+ 4 days) after IMP administration |
| Red Blood Cell count | Standard haematological parameter | 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 |
| White Blood Cell count | Standard haematological parameter | 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 |
| Haemoglobin levels | Standard haematological parameter | 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 |
| Haematocrit | Standard haematological parameter | 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 |
| Platelet count | Standard haematological parameter | 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 |
| University of Miami |
| Recruiting |
| Miami |
| Florida |
| 33136 |
| United States |
| Massachusetts General Hospital | Recruiting | Boston | Massachusetts | 02114 | United States |
| Duke University Medical Center | Recruiting | Durham | North Carolina | 27710-1000 | United States |
| Atrium Health Wake Forest Baptist | Recruiting | Winston-Salem | North Carolina | 27157 | United States |
| Cleveland Clinic | Not yet recruiting | Cleveland | Ohio | 44195 | United States |
| The Ohio State University | Recruiting | Columbus | Ohio | 43214 | United States |
| OU Health University of Oklahoma Medical Center | Recruiting | Oklahoma City | Oklahoma | 73104 | United States |
| University of Texas Southwestern Medical Center | Recruiting | Dallas | Texas | 75390 | United States |
| University Hospital Innsbruck | Recruiting | Innsbruck | Austria |
| Vienna General Hospital AKH, Medical University of Vienna | Recruiting | Vienna | Austria |
| Royal Columbian Hospital | Recruiting | New Westminster | British Columbia | V3L0A4 | Canada |
| Kingston Health Sciences Centre | Recruiting | Kingston | Ontario | K7L2V7 | Canada |
| Toronto General Hospital | Recruiting | Toronto | Ontario | M5G2C4 | Canada |
| Montreal Heart Institute | Recruiting | Montreal | Quebec | H1T1C8 | Canada |
| Center of Cardiovascular and Transplant Surgery | Recruiting | Brno | Czechia |
| Institute for Clinical and Experimental Medicine | Recruiting | Prague | Czechia |
| CHU de Reims, Hôpital Robert Debré | Terminated | Reims | France |
| CHU de Rennes | Withdrawn | Rennes | France |
| Hospital of Lithuanian university of Health sciences Kauno Klinikos | Recruiting | Kaunas | Lithuania |
| Vilnius University hospital Santaros Klinikos | Recruiting | Vilnius | Lithuania |
| Institute for Cardiovascular Diseases C.C. Iliescu | Recruiting | Bucharest | Romania |
| Institute of Cardiovascular Diseases Vojvodina | Not yet recruiting | Kamenitz | Serbia |
| University Medical Centre Ljubljana | Recruiting | Ljubljana | Slovenia |
| Royal Papworth Hospital | Recruiting | Cambridge | United Kingdom |
| University Hospital Coventry and Warwickshire | Recruiting | Coventry | United Kingdom |
| The James Cook University Hospital | Recruiting | Middlesbrough | United Kingdom |
| ID | Term |
|---|---|
| D020152 | Antithrombin III Deficiency |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001796 | Blood Protein Disorders |
| D019851 | Thrombophilia |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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