Findings published in the peer-reviewed Journal of Cardiothoracic and Vascular Anesthesia
Secondary findings do not change the primary outcomes of the FIBRES trial
PARAMUS, N.J. and TORONTO, Sept. 9, 2026 /PRNewswire/ -- A prespecified secondary analysis of the landmark FIBRES trial demonstrated that fibryga® (fibrinogen [human]) significantly reduced 24-hour allogeneic blood-product (ABP) transfusion requirements versus cryoprecipitate in two predefined, overlapping subgroups: patients in a non-critical state before surgery and patients undergoing elective surgery.1
These findings have been published as a peer-reviewed article in the Journal of Cardiothoracic and Vascular Anesthesia, titled Superiority of Fibrinogen Concentrate Versus Cryoprecipitate for Treatment of Bleeding in Cardiac Surgery Patients: A Secondary Analysis of the FIBRES Randomized Clinical Trial Stratified by Surgical Risk.
The newly published analysis evaluated two subgroups that had been defined before the trial results were analyzed. Results from this analysis do not change the primary conclusion of the primary FIBRES trial. In the overall study population, fibryga® met the trial's prespecified criterion for non-inferiority to cryoprecipitate.2,3
"These findings provide additional evidence and guidance around fibrinogen replacement in cardiac surgery patients who develop clinically significant bleeding and acquired hypofibrinogenemia," said Justyna Bartoszko, M.D., lead author of the analysis and a member of the FIBRES Research Group. "Blood transfusions can be lifesaving, but an efficient patient blood management strategy seeks to avoid unnecessary exposure to allogeneic blood components, as they are known to increase the risk of postoperative complications."4
Findings from the secondary subgroup analysis
The first subgroup consisted of participants from the FIBRES trial who were determined to be in a non-critical state before surgery (n=634), representing 86% of the primary analysis population. In this subgroup, there was a 19% relative reduction in ABP units transfused within 24 hours in patients receiving fibryga® versus cryoprecipitate (13.6 units vs. 16.2 units).
The second subgroup consisted of FIBRES trial participants undergoing elective surgery (n=466), representing 63% of the primary analysis population. In this subgroup, there was a 19% relative reduction in ABP units transfused within 24 hours in patients receiving fibryga® versus cryoprecipitate (11.7 units vs. 14.4 units).
"When clinically appropriate for a patient with acquired fibrinogen deficiency, a standardized fibrinogen concentrate provides targeted replacement," said Huub Kreuwel, Ph.D., Vice President of Medical Affairs, Octapharma USA.5 "While the primary results from FIBRES have not changed, secondary analyses such as these provide relevant information about specific patient subgroups which may be useful for informing institutional patient blood management protocols."
Safety findings
In the full study population, 248 (66.7%) patients in the fibryga® group and 264 (72.7%) patients in the cryoprecipitate group experienced treatment-emergent adverse events during the study (relative risk, 0.92; 95% CI, 0.83-1.01; P=0.07).
Within the elective-surgery subgroup, adverse events were less frequent among patients assigned to fibryga® than among patients assigned to cryoprecipitate (relative risk, 0.85; 95% CI, 0.75-0.97; P=0.02). Serious adverse events were also less frequent among fibryga® recipients in the elective surgery subgroup (relative risk, 0.71; 95% CI, 0.52-0.99; P=0.04).
No treatment-emergent AEs, SAEs, or deaths in the study were deemed to be possibly or probably related to FC or cryoprecipitate.
These findings should not be interpreted as establishing an overall safety advantage, and the safety of fibryga® should be evaluated in accordance with its current U.S. prescribing information.
About the FIBRES trial
The U.S. Food and Drug Administration's approval of fibryga® for fibrinogen replacement in patients with acquired fibrinogen deficiency (AFD) was supported by the landmark FIBRES study published in JAMA. The study demonstrated that fibrinogen concentrate is non-inferior to cryoprecipitate in managing bleeding following cardiac surgery, with the added benefits of standardized dosing, faster preparation, and reduced risk of viral transmission.
FIBRES was an investigator-initiated, pragmatic, multicenter, randomized clinical trial conducted at 11 Canadian hospitals (ClinicalTrials.gov Identifier NCT03037424). The study enrolled adults undergoing cardiac surgery who developed clinically significant bleeding and acquired hypofibrinogenemia after cardiopulmonary bypass for whom fibrinogen replacement was ordered. The FIBRES trial was supported by an unrestricted grant from Octapharma, which also provided the fibrinogen concentrate used in the study. Funding was also provided by the Canadian Institutes of Health Research. Cryoprecipitate was provided by Canadian Blood Services and Héma-Québec. Full author disclosures are reported in the published article.
A total of 827 patients were randomized. Of these, 735 patients received study treatment and were included in the primary analysis: 372 received fibryga® and 363 received cryoprecipitate. Each ordered dose consisted of 4 grams of fibryga® or 10 units of cryoprecipitate during the first 24 hours after cardiopulmonary bypass.
The primary endpoint was the cumulative number of allogeneic blood-component units – red blood cells, platelets and plasma – administered during the first 24 hours after bypass. In the overall population, the mean number of blood-component units administered was 16.3 with fibryga® and 17.0 with cryoprecipitate. The ratio of the means was 0.96, with a two-sided 95% confidence interval of 0.84 to 1.09. The trial met its prespecified non-inferiority criterion, with P0.001 for non-inferiority. The test for superiority in the overall population was not statistically significant, with P=0.50.
About fibryga®
fibryga® is a human fibrinogen concentrate indicated for: fibrinogen supplementation in bleeding patients with acquired fibrinogen deficiency; and treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia.
fibryga® is not indicated for dysfibrinogenemia.
Contraindications
Anaphylactic or severe reactions to fibryga® or its components (Sodium Citrate Dihydrate; Glycine; L-Arginine Hydrochloride).
Warnings and Precautions
Monitor patients for early signs of hypersensitivity or allergic reactions. If necessary, discontinue administration and institute appropriate treatment.
Thrombotic events have been reported in patients receiving fibryga®. Treatment with human fibrinogen concentrate in congenital fibrinogen deficiency has been associated with thrombosis at target plasma fibrinogen levels that were below 150 mg/dL. The thrombotic risks may be greater when the target fibrinogen plasma level is 150 mg/dL. Weigh the benefits of administration versus the risks of thrombosis.
fibryga® is made from pooled human plasma. Products made from human plasma may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
Adverse Reactions
The most serious adverse reactions that may be observed with fibryga® are thromboembolic episodes and anaphylactic-type reactions. The most common adverse reactions observed in clinical studies with fibryga® in acquired fibrinogen deficiency (>5% of patients) were abnormal hepatic function, acute kidney injury, anemia, atrial fibrillation, delirium and renal failure.
The most common adverse reactions observed in clinical studies with fibryga® in congenital fibrinogen deficiency (>5% of patients) were nausea, vomiting, pyrexia (fever), and thrombocytosis.
For full prescribing information, please visit fibrygausa.com/pi. For more information on fibryga®, please visit fibrygausa.com.
About Octapharma
Octapharma is one of the world's largest human protein manufacturers, developing and producing therapies from human plasma and human cell lines. Headquartered in Lachen, Switzerland, Octapharma has over 11,000 employees and serves patients in 117 countries across Immunotherapy, Hematology, and Critical Care.
With seven R&D sites, five manufacturing facilities in Europe, and more than 200 plasma donation centers in the U.S. and Europe, Octapharma has delivered trusted therapies for over 40 years. The company is committed to improving lives through innovation, quality, and a deep focus on patient care and clinical partnership. To learn more please visit www.octapharma.com.
References
- Bartoszko J, Karkouti K, Callum JL; FIBRES Research Group. Superiority of Fibrinogen Concentrate Versus Cryoprecipitate for Treatment of Bleeding in Cardiac Surgery Patients: A Secondary Analysis of the FIBRES Randomized Clinical Trial Stratified by Surgical Risk. J Cardiothorac Vasc Anesth. Published online June 17, 2026. doi:10.1053/j.jvca.2026.06.019.
- Callum JL, Farkouh ME, Scales DC, et al.; FIBRES Research Group. Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery: The FIBRES Randomized Clinical Trial. JAMA. 2019;322(20):1966-1976. doi:10.1001/jama.2019.17312.
- Fibryga® [Fibrinogen (Human)]. U.S. Prescribing Information. Octapharma USA, Inc. Revised August 2025.
- U.S. Centers for Disease Control and Prevention. The National Healthcare Safety Network (NHSN) Manual: Biovigilance Component Hemovigilance Module Protocol. Version 3.0. January 2026.
- Prokopchuk-Gauk O, Shih A, Nahirniak S, et al. NAC Statement on Fibrinogen Concentrate Use in Acquired Hypofibrinogenemia. National Advisory Committee on Blood and Blood Products. December 15, 2014 [last updated February 26, 2025]. Available at: https://nacblood.ca/en/resource/nac-statement-fibrinogen-concentrate-use-acquired-hypofibrinogenemia.
