Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
Institute of Clinical and Translational Science, Nara Medical University, Kashihara, Nara, Japan.
BMJ Open. 2023 Jul 10;13(7):e072565. doi: 10.1136/bmjopen-2023-072565.
Emicizumab prophylaxis substantially reduces bleeding episodes in patients with haemophilia A (HA). The haemostatic efficacy of emicizumab in patients with HA is estimated as approximately 15% based on mimic activity of factor (F) VIII. Although it has been proven effective in preventing bleeding, its haemostatic effect during breakthrough bleeding or surgery is considered insufficient. Therefore, haemostatic management of emicizumab-treated patients with HA without inhibitors frequently requires FVIII replacement therapy. In haemostatic management of emicizumab-treated patients with HA, conventional FVIII dosage calculations are used in clinical practice without considering the coagulant effects of emicizumab.
In the CAGUYAMA study, 100 patients with HA without inhibitors will be enrolled for a maximum duration of 1 year, and samples of 30 events following the concomitant use of FVIII concentrates (30±5 U/kg) with emicizumab will be collected. An 'event' is defined as obtaining blood samples at preadministration and postadministration of FVIII concentrates during a breakthrough bleeding or a surgical procedure. Global coagulation assays will be used to measure the coagulation potential of the obtained samples. Clot waveform analysis (CWA) is used to identify the primary end-point, that is, the degree of improvement in the maximum coagulation rate at preadministration and post-administration of fixed-dose FVIII concentrations. The parameter obtained from CWA, which is triggered by an optimally diluted mixture of prothrombin time reagent and activated partial thromboplastin time reagent, is reported to be an excellent marker for assessing the degree of improvement of the coagulation potential in emicizumab-treated plasmas.
The CAGUYAMA study was approved by the Japan-Certified Review Board of Nara Medical University (Approval ID; nara0031). The study results will be communicated through publication in international scientific journals and presentations at (inter)national conferences.
jRCTs051210137.
依库珠单抗预防治疗可显著减少 A 型血友病（HA）患者的出血事件。根据因子（F）VIII 模拟活性，依库珠单抗治疗 HA 患者的止血效果约为 15%。尽管它已被证明可有效预防出血，但在突破性出血或手术期间，其止血效果被认为不足。因此，无抑制剂的 HA 依库珠单抗治疗患者的止血管理通常需要 FVIII 替代疗法。在 HA 依库珠单抗治疗患者的止血管理中，临床实践中使用传统的 FVIII 剂量计算方法，而不考虑依库珠单抗的凝血效应。
在 CAGUYAMA 研究中，将招募 100 名无抑制剂的 HA 患者，最长随访时间为 1 年，并在依库珠单抗与 FVIII 浓缩物（30±5 U/kg）联合使用后收集 30 个事件的样本。“事件”定义为在突破性出血或手术过程中获得 FVIII 浓缩物给药前和给药后的血液样本。将使用全球凝血检测来测量获得的样本的凝血潜能。凝血波形分析（CWA）用于确定主要终点，即在固定剂量 FVIII 浓度给药前和给药后的最大凝血速率的改善程度。CWA 获得的参数，由优化稀释的凝血酶原时间试剂和活化部分凝血活酶时间试剂混合物触发，被报道为评估依库珠单抗治疗血浆凝血潜能改善程度的极好标志物。
CAGUYAMA 研究已获得奈良医科大学日本认证审查委员会的批准（批准 ID：nara0031）。研究结果将通过在国际科学期刊上发表和在（国际）会议上展示来进行交流。
jRCTs051210137。
