Post‐authorization safety study of Clottafact<sup>®</sup>, a triply secured fibrinogen concentrate in congenital afibrinogenemia. A prospective observational study

Négrier, Claude; Rothschild, Chantal; Borg, Jeanne‐Yvonne; Lambert, Thierry; Claeyssens, S.; Sanhès, Laurence; Stieltjes, N.; Bertrand, Anne Marie; Andre, M; Sié, P.; Gruel, Yves; Tellier, Z.

doi:10.1111/vox.12424

Cited by 16 publications

(25 citation statements)

References 17 publications

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“…Allergic or hypersensitivity reactions are a known risk of fibrinogen and other coagulation factor concentrates, with anaphylactic shock, urticaria, and rash all having been previously reported . In the present study, a single mild skin reaction was reported.…”

Section: Discussionsupporting

confidence: 63%

“…A retrospective analysis of 12 patients with congenital fibrinogen deficiency treated with Haemocomplettan ® P rated hemostatic efficacy as very good (the highest rating) for all 26 BEs; however, these data were based on a subjective scoring system without independent adjudication . In a postauthorization study of Clottafact ® , five patients with afibrinogenemia received 48 infusions for treatment of 49 hemorrhagic events, with efficacy rated as excellent for 27 and good for 21 infusions, giving a success rate (rating of excellent/good) of 100% using an objective 4‐point scale …”

Section: Discussionmentioning

confidence: 99%

“…Data regarding the response of adolescent and pediatric patients to fibrinogen concentrate are scarce, with previous studies not including a sufficient number of patients to allow a meaningful comparison of the different age groups. A study evaluating Clottafact ® as prophylaxis demonstrated clinical efficacy of 98.8% for patients aged under 12 years and 100% for those aged 12 years or older; however, there were only four and five patients in these age groups, respectively …”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…26 Supplementary fibrinogen infusions are required in the postsurgical period to target fibrinogen levels at least >1 g L −1 until haemostasis is achieved and above 0.5 g L −1 until wound healing is complete. 25 The mean doses for prophylaxis ranged from 20 to 80 mg kg −1 in the youngest patients, reflecting the possibility of PK variability across age sub-groups as described for other fibrinogen concentrates. 25 The mean doses for prophylaxis ranged from 20 to 80 mg kg −1 in the youngest patients, reflecting the possibility of PK variability across age sub-groups as described for other fibrinogen concentrates.…”

Section: Effi C Ac Ymentioning

confidence: 98%

“…In the study of Manco-Johnson et al, 17 two patients experienced four mild adverse events between 72 hours and 9 days after Haemocomplettan P ® infusion. 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. 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.…”

Section: Safe T Ymentioning

confidence: 99%

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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Observational Safety Study of Clottafact® Fibrinogen Concentrate: Real-World Data in Mexico

et al. 2020

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Background and Objective The use of fibrinogen concentrate to treat or prevent major bleeding with regard to potential adverse reactions has not been free of controversy. Our objective was to perform a post-authorization safety study to describe the use of Clottafact ® (LFB Biomedicaments) fibrinogen concentrate in real-life medical practice in Mexico. Methods This was a prospective, observational study that collected and evaluated information between January 2017 and June 2019 related to suspected serious adverse reactions (SUSARs) during and after Clottafact ® infusion. Results Information from 40 subjects was analyzed; 43% were women (n = 17), mean age was 39.05 ± 26.8 years (range 0-91 years). The medical specialties included in this analysis were cardiac surgery − 52.5% of the cases, gynecology/obstetrics − 17.5%, general surgery and orthopedics − 12.5% each, and hematology and neurosurgery − 2.5%, respectively. Mean plasma fibrinogen levels before and after Clottafact ® infusion were 2.58 g/L and 4.02 g/L; p = 0.001, respectively. The mean Clottafact ® dose was 2.20 ± 0.77 g. One patient presented SUSARs (dry mouth and dysgeusia) with drug administration, which ceased after treatment discontinuation. Conclusions In this real-life post-marketing study, the safety profile of Clottafact ® was very similar to previous reports. Thus, Clottafact ® shows a favorable safety profile in clinical practice. Key Points Clottafact ® showed a favorable safety profile in clinical practice in Mexico. Clottafact® human fibrinogen concentrate usage profile is considered safe in real-world conditions for the treatment of acquired or congenital fibrinogen deficiency.

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Post‐authorization safety study of Clottafact^®, a triply secured fibrinogen concentrate in congenital afibrinogenemia. A prospective observational study

Abstract: This study confirms that the benefit/risk balance for this fibrinogen concentrate is favourable.

Cited by 16 publications

References 17 publications

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

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

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

Observational Safety Study of Clottafact® Fibrinogen Concentrate: Real-World Data in Mexico

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Post‐authorization safety study of Clottafact®, a triply secured fibrinogen concentrate in congenital afibrinogenemia. A prospective observational study

Abstract: This study confirms that the benefit/risk balance for this fibrinogen concentrate is favourable.

Cited by 16 publications

References 17 publications

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

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

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

Observational Safety Study of Clottafact® Fibrinogen Concentrate: Real-World Data in Mexico

Contact Info

Product

Resources

About

Post‐authorization safety study of Clottafact^®, a triply secured fibrinogen concentrate in congenital afibrinogenemia. A prospective observational study