Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency

Ross, Cecil; Rangarajan, Savita; Karimi, Mehran; Toogeh, Gholamreza; Apte, Shashikant; Lissitchkov, Toshko; Acharya, Suchitra S.; Manco‐Johnson, M. J.; Srivastava, Alok; Brand, Brigitte; Schwartz, Bruce A.; Knaub, Sigurd; Peyvandi, Flora

doi:10.1111/jth.13923

Cited by 34 publications

(75 citation statements)

References 17 publications

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“…20 The PK profiles of the two fibrinogen concentrates randomized in the study were similar, with some exceptions. 20 The PK profiles of the two fibrinogen concentrates randomized in the study were similar, with some exceptions.…”

Section: Pharmacokine Tic Propertie Smentioning

confidence: 82%

“…20 Fibrinogen activity was measured using a modified Clauss assay with a detection limit of 0.2 g L −1 . 20 Fibrinogen activity was measured using a modified Clauss assay with a detection limit of 0.2 g L −1 .…”

Section: Pharmacokine Tic Propertie Smentioning

confidence: 99%

“…25 Among the 16 adverse events following Fibryga ® infusions reported in the interim FORMA-02, only a mild skin reaction was deemed possibly related to the infusion. 20 Eleven adverse events in seven patients were considered related to infusions of FibCLOT ® , including five severe (splenic rupture, ovarian cyst rupture, haemorrhagic shock, joint dislocation, bone pain), four moderate and two mild. 20 Eleven adverse events in seven patients were considered related to infusions of FibCLOT ® , including five severe (splenic rupture, ovarian cyst rupture, haemorrhagic shock, joint dislocation, bone pain), four moderate and two mild.…”

Section: Safe T Ymentioning

confidence: 99%

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Fibrinogen concentrates in hereditary fibrinogen disorders: Past, present and future

Casini

Moerloose²

2019

Haemophilia

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Hereditary fibrinogen disorders (HFD) are rare coagulation disorders resulting from mono-or bi-allelic mutations in fibrinogen genes. 1According to the levels of fibrinogen activity and antigen, HFD are classified into quantitative (afibrinogenemia and hypofibrinogenemia) or qualitative (dysfibrinogenemia and hypodysfibrinogenemia) disorders. 2 The spectrum of symptoms is broad and heterogeneous among patients with HFD, even if bleeding is the most common complication of all HFD sub-types. 3 The bleeding phenotype is mostly correlated to the fibrinogen level, 4 ranging from life-threatening haemorrhage to postsurgical bleeding. In afibrinogenemia, the majority of patients suffer from severe bleeding such as umbilical cord bleeds, muscle haematomas, haemarthroses and bleeding in the central nervous system. 5 Paradoxically, thrombotic events can occur in patients with afibrinogenemia, even in the absence of fibrinogen administration. 6 In hypofibrinogenemia, spontaneous bleeding is less frequent and complications are mainly associated with trauma or surgery. 7 In dysfibrinogenemia, the cumulative incidence of major bleeding has been estimated to be about 19% at 50 years of age. 8 However, some dysfibrinogen variants are strongly associated with an increased risk of thrombosis. 9 In all types of HFD, surgery and pregnancy are high-risk bleeding situations.As for most coagulation factor deficiencies, in HFD, the bleeding prevention and management is based on replacement of the lacking protein. Three sources of fibrinogen are currently available: fresh frozen plasma, cryoprecipitate and lyophilized fibrinogen concentrate. 10 The latter is the best option, although still not widely available. It confers several advantages compared to fresh frozen plasma and cryoprecipitate: (a) it represents a safer therapeutic option due AbstractHereditary fibrinogen disorders (HFD) are rare coagulation disorders. Even if the spectrum of symptoms is broad depending on the sub-type, bleeding is the most common complication. Of the available sources of fibrinogen replacement, fibrinogen concentrate provides a safer and more effective option to treat and prevent bleeding.Recent clinical trials on established and new fibrinogen concentrates have increased our knowledge on the clinical pharmacology of these products, pointing out possible age and weight differences for dose adjustment. The efficacy of fibrinogen infusions has been demonstrated, especially for the management of acute bleeding with an excellent response based on investigator rating. The target fibrinogen levels in the setting of both minor and major surgeries have been better specified. The safety has been confirmed with a low number of adverse events but there still remains concern over possible thrombotic risks. Pharmacological, clinical aspects and future perspectives on the utilization of fibrinogen concentrates in the treatment and prevention of bleeding in patients with HFD are reviewed.

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Section: Pharmacokine Tic Propertie Smentioning

confidence: 82%

Section: Pharmacokine Tic Propertie Smentioning

confidence: 99%

Section: Safe T Ymentioning

confidence: 99%

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Fibrinogen concentrates in hereditary fibrinogen disorders: Past, present and future

Casini

Moerloose²

2019

Haemophilia

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“…The pharmacokinetic (PK) profile of this HFC was previously investigated in a randomized, cross‐over comparative study. The PK properties were broadly comparable between the new HFC and a currently marketed comparator HFC (Haemocomplettan ® P [RiaSTAP ® ]), with the exception of AUC norm , which was significantly larger, and clearance, which was significantly slower, for the new HFC in patients with afibrinogenemia . The HFC used in this study is now licensed in multiple countries for the treatment of acute bleeding and for surgical prophylaxis in patients with fibrinogen deficiency, with approval obtained on the basis of a planned interim analysis of the present study .…”

Section: Introductionmentioning

confidence: 81%

“…For consistency, frozen samples were transferred to a central laboratory for testing. MCF was determined by performing thromboelastometry (ROTEM) on thawed plasma samples, as previously described …”

Section: Methodsmentioning

confidence: 99%

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients

Lissitchkov

Madan

Khayat

et al. 2020

Journal of Thrombosis and Haemostasis

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Background Congenital fibrinogen deficiency is an ultra‐rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder. Methods Hemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA®, Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four‐point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined. Results Twenty‐five afibrinogenemia patients were treated with HFC: 24 for on‐demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92‐0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95‐0.999). Mean ± standard deviation (SD) increase in MCF was 5.8 ± 2.5 mm one hour after the first HFC infusion (mean ± SD dose, 61.88 ± 11.73 mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80 mg/kg [34.09‐225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82‐1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies. Conclusions Human fibrinogen concentrate was efficacious for on‐demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia.

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Viscoelastic Hemostatic Tests and Fibrinogen Concentrations in Trauma

Peng

Beckett

2022

Biomarkers in Trauma, Injury and Critical Care

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Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency

Cited by 34 publications

References 17 publications

Fibrinogen concentrates in hereditary fibrinogen disorders: Past, present and future

Fibrinogen concentrates in hereditary fibrinogen disorders: Past, present and future

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients

Viscoelastic Hemostatic Tests and Fibrinogen Concentrations in Trauma

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