Clinical pharmacology, efficacy and safety study of a triple-secured fibrinogen concentrate in adults and adolescent patients with congenital fibrinogen deficiency.
Fibrinogen concentrate vs. fresh frozen plasma for the management of coagulopathy during thoraco-abdominal aortic aneurysm surgery: a pilot randomised controlled trial
Background: Single-factor replacement therapy is considered the most suitable treatment option for hereditary fibrinogen deficiency. A triple-secured plasma-derived human fibrinogen product was developed to increase the safety of the former fibrinogen concentrate.
Objectives: This non-randomized, open-label, prospective study investigated pharmacokinetics, efficacy, and safety of a novel fibrinogen concentrate (FibCLOT®/CLOTTAFACT® LFB, France) in inherited deficiency.
Patients/Methods: Fourteen patients ≥40 kg received fibrinogen concentrate for pharmacology and 16 ≥ 23 kg received treatment for bleeding or surgery. Each treatment was followed by a 3-week safety observation period. Key outcomes included number of infusions, dose, bleeding control, daily assessment, hemoglobin, blood loss, transfusions, and physicians’ global assessment of response.
Results: Incremental recovery was 2.35 mg mL−1 per mg kg−1 and maximal concentration 1.41 g L−1 (geometric mean) after 0.060 g kg−1 infusion in 14 afibrinogenemic patients. Terminal half-life was 69.3 h (non-compartmental analysis). The maximum clot firmness was increased by a mean of 10.3 mm from baseline to maximal effect. Sixteen patients participated to the efficacy phase: 32 bleeding episodes were treated in 9 patients, and 15 patients underwent 38 surgical/invasive procedures. All patients achieved appropriate hemostasis: response to treatment was successful in all bleeds (95% CI, 0.89–1.00) and procedures (95% CI, 0.91–1.00). Most (94%) bleeds were controlled with a single infusion (median 0.050 g kg−1). Two patients experienced asymptomatic distal venous thromboses identified by systematic ultrasound.
Conclusion: FibCLOT®/CLOTTAFACT® showed a pharmacokinetic profile comparable to that of other fibrinogen concentrates and provides safe and clinically effective substitution therapy for fibrinogen-deficient patients.