Journal of clinical anesthesia · 2026
Efficacy and safety of fibrinogen concentrate (BT524) in severe hemorrhage: Phase 3 subcohort analysis of the AdFIrst trial in patients undergoing cytoreductive surgery for pseudomyxoma peritonei.
СтатьяКлиническое исследование III фазыРандомизированное исследованиеEquivalence TrialНазвание и аннотация: Перевод в очереди
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Roy Ashok, Stanford Sophia, Cecil Tom, Preston Nicola, Rowley Jessica, Porter Pennie, Schimo Sonja, Abraha Salomon, Staus Alexander, Balaban Ümniye, Wessels-Kranz Judith, Schüttrumpf Jörg, Aigner Silke, Böhm Heike, Rahe-Meyer Niels
Аннотация
BACKGROUND: The AdFIrst phase 3 trial evaluated the efficacy and safety of human fibrinogen concentrate (FC) versus standard of care for major bleeding in complex surgery. This subanalysis evaluated a preemptive hemostatic strategy using FC versus cryoprecipitate (Cryo) to manage severe bleeding patients undergoing major abdominal surgery, specifically cytoreductive surgery (CRS) for pseudomyxoma peritonei (PMP).
METHODS: A single-center UK analysis derived from a randomized, active-controlled, partially blinded, phase 3, non-inferiority trial. Patients undergoing PMP surgery with predicted intraoperative blood loss >2 L were randomized (1:1) to receive either FC (4 g) or two pools of Cryo (10 units) with repeat dosing as required. The primary endpoint was intraoperative blood loss, measured from the decision to treat the patient with trial drug until the end of surgery with a non-inferiority margin of 150 mL (ClinicalTrials.gov: NCT03444324).
RESULTS: Between March 2021 and September 2023, 98 patients (48 FC; 50 Cryo) were enrolled, randomized, and evaluated. The primary endpoint was met: Least squares mean intraoperative blood loss was 1517 mL (95% CI, 1331-1703) with FC and 1706 mL (95% CI, 1524-1889) with Cryo, corresponding to a difference of -190 mL (95% CI, -450 to 71; nominal exploratory p = 0.011). The upper bound of the 95% CI was below the prespecified non-inferiority margin, consistent with the non-inferiority observed in the overall trial. Thromboembolic events occurred in fewer patients in the FC group (3 [6.3%]) than in the Cryo group (11 [22%]; nominal exploratory p = 0.041); other safety outcomes were comparable between groups.
CONCLUSION: In patients undergoing CRS for PMP, these results provide supportive evidence for the hemostatic efficacy of FC, consistent with the overall trial and prior studies, with a favorable safety profile. In this single-center PMP subgroup, the findings support a preemptive fibrinogen strategy that may inform practice in other surgical settings and warrants evaluation in future studies.
METHODS: A single-center UK analysis derived from a randomized, active-controlled, partially blinded, phase 3, non-inferiority trial. Patients undergoing PMP surgery with predicted intraoperative blood loss >2 L were randomized (1:1) to receive either FC (4 g) or two pools of Cryo (10 units) with repeat dosing as required. The primary endpoint was intraoperative blood loss, measured from the decision to treat the patient with trial drug until the end of surgery with a non-inferiority margin of 150 mL (ClinicalTrials.gov: NCT03444324).
RESULTS: Between March 2021 and September 2023, 98 patients (48 FC; 50 Cryo) were enrolled, randomized, and evaluated. The primary endpoint was met: Least squares mean intraoperative blood loss was 1517 mL (95% CI, 1331-1703) with FC and 1706 mL (95% CI, 1524-1889) with Cryo, corresponding to a difference of -190 mL (95% CI, -450 to 71; nominal exploratory p = 0.011). The upper bound of the 95% CI was below the prespecified non-inferiority margin, consistent with the non-inferiority observed in the overall trial. Thromboembolic events occurred in fewer patients in the FC group (3 [6.3%]) than in the Cryo group (11 [22%]; nominal exploratory p = 0.041); other safety outcomes were comparable between groups.
CONCLUSION: In patients undergoing CRS for PMP, these results provide supportive evidence for the hemostatic efficacy of FC, consistent with the overall trial and prior studies, with a favorable safety profile. In this single-center PMP subgroup, the findings support a preemptive fibrinogen strategy that may inform practice in other surgical settings and warrants evaluation in future studies.