Department of Pediatrics, Hotel Dieu de France, Beirut, Lebanon.
Children's Hospital, Mohamed V University, Rabat, Morocco.
J Thromb Haemost. 2019 Apr;17(4):635-644. doi: 10.1111/jth.14392. Epub 2019 Feb 20.
Essentials A novel fibrinogen concentrate was evaluated in patients with congenital fibrinogen deficiency. An open-label, phase 2-3 trial studied pharmacology, efficacy, and safety in patients >6 years. The product offers safe and effective therapy in the treatment and prophylaxis of bleeding. Data in recovery show the need of adjusted treatment and further investigation in children. SUMMARY: 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 per mg kg and maximal concentration 1.41 g L (geometric mean) after 0.060 g kg 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 ). 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.
一种新型纤维蛋白原浓缩物在先天性纤维蛋白原缺乏症患者中进行了评估。一项开放标签、2-3 期临床试验研究了该产品在>6 岁患者中的药代动力学、疗效和安全性。该产品在治疗和预防出血方面提供了安全有效的治疗。恢复数据表明，需要在儿童中调整治疗并进一步研究。
背景 单因子替代疗法被认为是遗传性纤维蛋白原缺乏症最适宜的治疗选择。一种三重安全的血浆源性人纤维蛋白原产品被开发出来，以提高前纤维蛋白原浓缩物的安全性。
目的 本非随机、开放标签、前瞻性研究调查了新型纤维蛋白原浓缩物（FibCLOT / CLOTTAFACT LFB，法国）在遗传性缺乏症中的药代动力学、疗效和安全性。
患者/方法 14 名≥40 kg 的患者接受纤维蛋白原浓缩物进行药理学研究，16 名≥23 kg 的患者接受出血或手术治疗。每次治疗后均进行为期 3 周的安全性观察期。主要终点包括输注次数、剂量、出血控制、日常评估、血红蛋白、失血量、输血和医生对反应的总体评估。
结果 在 14 名无纤维蛋白原血症患者中，输注 0.060 g/kg 后，增量恢复为 2.35 mg mL /每毫克公斤，最大浓度为 1.41 g L（几何平均值）。末端半衰期为 69.3 h（非房室分析）。最大凝块硬度平均增加 10.3 mm，与基线相比达到最大效果。16 名患者参加了疗效阶段：9 名患者共发生 32 次出血事件，15 名患者共进行了 38 次手术/有创性操作。所有患者均达到适当的止血：所有出血（95%CI，0.89-1.00）和手术（95%CI，0.91-1.00）的治疗反应均成功。大多数（94%）出血仅需单次输注（中位数 0.050 g/kg）即可控制。2 名患者出现无症状的远端静脉血栓形成，通过系统超声发现。
结论 FibCLOT / CLOTTAFACT 的药代动力学特征与其他纤维蛋白原浓缩物相似，可为纤维蛋白原缺乏症患者提供安全有效的替代治疗。
