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This is a pragmatic, prospective, multi-center, randomized, active-control, single-blinded, non-inferiority phase 3 trial in adult cardiac surgical patients. Up to 12 Canadian hospitals will participate, and the trial will require up to 2 years for patient recruitment.
Twelve-hundred bleeding adult cardiac surgical patients who require fibrinogen supplementation due to acquired hypofibrinogenemia after CPB will be included. Patients will be randomized to receive equivalent doses of either fibrinogen concentrate (Octafibrin) or cryoprecipitate when the blood bank receives the first order for fibrinogen supplementation and deems it to be in accordance with accepted clinical standards. Thereafter, patients will be treated according to their assigned group each time fibrinogen supplementation is ordered during the treatment period (24 hours after termination of CPB). No other aspects of care will be modified.
The primary efficacy outcome will be the number of Allogeneic blood products (ABP) (red blood cells [RBCs], pooled or apheresis platelets, and plasma) administered during the first 24 hours after termination of CPB. Safety outcomes will be measured for the first 28 days after surgery, which is the duration of participation of each patient in the trial. Comparisons will be by intention-to-treat (ITT) (primary) and per-protocol (PP) analysis. One interim analysis will be conducted after 600 patients have been treated to determine whether the study should be terminated for safety reasons, demonstrated non-inferiority or futility reasons.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fibrinogen concentrate Octafibrin | Active Comparator |
| |
| Cryoprecipitate | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Octafibrin | Drug | Octafibrin will be administered when the blood bank receives an order for fibrinogen supplementation |
|
| Measure | Description | Time Frame |
|---|---|---|
| The primary endpoint, which is of efficacy, is the comparison of the total number of units of ABPs (RBCs, pooled or apheresis platelets, and plasma) administered during the first 24 hours after termination of CPB. | The number of ABPs (red blood cells [RBCs], pooled or apheresis platelets, and plasma) administered during the first 24 hours after termination of CPB | 24 hours |
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Inclusion Criteria:
1. Patients undergoing index cardiac surgery with CPB in whom fibrinogen supplementation is ordered in accordance with accepted clinical standards (significant hemorrhage and known or presumed hypofibrinogenemia).
Exclusion Criteria:
1. Receipt of fibrinogen rich products (fibrinogen concentrate or cryoprecipitate) within 24 hours before surgery 2. History of severe allergic reaction to cryoprecipitate or fibrinogen concentrate 3. Refusal of ABPs, fibrinogen concentrate or cryoprecipitate due to religious or other reasons 4. Fibrinogen level known to be >3.0 g/L within 30 minutes of IMP order (to eliminate the risk of raising patients' fibrinogen levels to >4.0 g/L with supplementation 5. Known pregnancy
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| Name | Affiliation | Role |
|---|---|---|
| Keyvan Karkouti, MD | University Health Network, Toronto | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fraser University Royal Columbia | Vancouver | British Columbia | V3L 3W7 | Canada | ||
| University of Manitoba, St Boniface General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37588266 | Derived | Devine C, Bartoszko J, Callum J, Karkouti K; FIBRES Study Investigators. Weight-adjusted dosing of fibrinogen concentrate and cryoprecipitate in the treatment of hypofibrinogenaemic bleeding adult cardiac surgical patients: a post hoc analysis of the Fibrinogen Replenishment in cardiac surgery randomised controlled trial. BJA Open. 2022 Jun 9;2:100016. doi: 10.1016/j.bjao.2022.100016. eCollection 2022 Jun. | |
| 35773027 |
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| ID | Term |
|---|---|
| C026912 | cryoprecipitate coagulum |
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| Cryoprecipitate | Drug | Cryoprecipitate will be administered when the blood bank receives an order for fibrinogen supplementation |
|
| Winnipeg |
| Manitoba |
| R2H 2A6 |
| Canada |
| Hamilton Health Science Centre, McMaster University | Hamilton | Ontario | L8S 3Z5 | Canada |
| Kingston General Hsopital | Kingston | Ontario | K7L 3N6 | Canada |
| London Health Science Centre | London | Ontario | N6A 5A5 | Canada |
| University of Ottawa Heart Institute | Ottawa | Ontario | K1Y 4W7 | Canada |
| Sunnybrook Health Science Centre | Toronto | Ontario | M4N 3M5 | Canada |
| St Michael's Hospital | Toronto | Ontario | M5B 1W8 | Canada |
| Tornoto General Hospital, University Health Network | Toronto | Ontario | M5G 2C4 | Canada |
| Montreal Heart Institute | Montreal | Quebec | H1T 1C8 | Canada |
| Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval | Québec | G1V 4G5 | Canada |
| Derived |
| Bartoszko J, Martinez-Perez S, Callum J, Karkouti K; FIBRES Study Investigators. Impact of cardiopulmonary bypass duration on efficacy of fibrinogen replacement with cryoprecipitate compared with fibrinogen concentrate: a post hoc analysis of the Fibrinogen Replenishment in Surgery (FIBRES) randomised controlled trial. Br J Anaesth. 2022 Sep;129(3):294-307. doi: 10.1016/j.bja.2022.05.012. Epub 2022 Jun 28. |
| 31634905 | Derived | Callum J, Farkouh ME, Scales DC, Heddle NM, Crowther M, Rao V, Hucke HP, Carroll J, Grewal D, Brar S, Bussieres J, Grocott H, Harle C, Pavenski K, Rochon A, Saha T, Shepherd L, Syed S, Tran D, Wong D, Zeller M, Karkouti K; FIBRES Research Group. Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery: The FIBRES Randomized Clinical Trial. JAMA. 2019 Nov 26;322(20):1966-1976. doi: 10.1001/jama.2019.17312. |
| 29678987 | Derived | Karkouti K, Callum J, Rao V, Heddle N, Farkouh ME, Crowther MA, Scales DC. Protocol for a phase III, non-inferiority, randomised comparison of a new fibrinogen concentrate versus cryoprecipitate for treating acquired hypofibrinogenaemia in bleeding cardiac surgical patients: the FIBRES trial. BMJ Open. 2018 Apr 20;8(4):e020741. doi: 10.1136/bmjopen-2017-020741. |