Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada
Department of Anesthesia and Pain Management, University Health Network, Sinai Health, Women's College Hospital, Toronto, Ontario, Canada.
BMJ Open. 2024 Aug 21;14(8):e091381. doi: 10.1136/bmjopen-2024-091381.
Reduced thrombin generation is an important component of post cardiopulmonary bypass (CPB) coagulopathy. To replenish coagulation factors and enhance thrombin generation in bleeding surgical patients, frozen plasma (FP) and four-factor prothrombin complex concentrate (4F-PCC) are used. However, the efficacy-safety balance of 4F-PCC relative to FP in cardiac surgery is unconfirmed.
LEX-211 (FARES-II) is an active-control, randomised, phase 3 study comparing two coagulation factor replacement therapies in bleeding adult cardiac surgical patients at 12 hospitals in Canada and the USA. The primary objective is to determine whether 4F-PCC (Octaplex/Balfaxar, Octapharma) is clinically non-inferior to FP for haemostatic effectiveness. Inclusion criteria are any index (elective or non-elective) cardiac surgery employing CPB and coagulation factor replacement with 4F-PCC or FP ordered in the operating room for bleeding management. Patients will be randomised to receive 1500 or 2000 international units of 4F-PCC or 3 or 4 units of FP, depending on body weight. The primary endpoint of haemostatic treatment response is 'effective' if no additional haemostatic intervention is required from 60 min to 24 hours after the first initiation of 4F-PCC or FP; or 'ineffective' if any other haemostatic intervention (including a second dose of study drug) is required. An estimated 410 evaluable patients will be required to demonstrate non-inferiority (one-sided α of 0.025, power ≥90%, non-inferiority margin 0.10). Secondary outcomes include transfusions, bleeding-related clinical endpoints, coagulation parameters and safety.
The trial has been approved by the institutional review boards of all participating centres. Trial completion is anticipated at the end of 2024, and results will be disseminated via publications in peer-reviewed journals and conference presentations in 2025. The results will advance our understanding of coagulation management in bleeding surgical patients, potentially reducing the need for allogeneic blood products and improving outcomes in surgical patients.
NCT05523297.
体外循环（CPB）后凝血功能障碍的一个重要特征是凝血酶生成减少。为了补充出血手术患者的凝血因子并增强凝血酶生成，常使用冰冻血浆（FP）和四因子凝血酶原复合物浓缩物（4F-PCC）。然而，心脏手术中 4F-PCC 相对于 FP 的疗效-安全性平衡尚未得到证实。
LEX-211（FARES-II）是一项活性对照、随机、3 期研究，在加拿大和美国的 12 家医院比较了两种凝血因子替代疗法在出血成年心脏手术患者中的应用。主要目的是确定 4F-PCC（Octaplex/Balfaxar，Octapharma）在止血效果方面是否不劣于 FP。纳入标准为任何指数（选择性或非选择性）心脏手术，CPB 术后使用 4F-PCC 或 FP 进行凝血因子替代治疗，且在手术室中为出血管理开医嘱使用 4F-PCC 或 FP。根据体重，患者将被随机分配接受 1500 或 2000 国际单位的 4F-PCC 或 3 或 4 单位的 FP。止血治疗反应的主要终点为：4F-PCC 或 FP 首次给药后 60 分钟至 24 小时内无需进行任何其他止血干预为“有效”；或需要任何其他止血干预（包括研究药物的第二剂）为“无效”。预计需要 410 名可评估患者来证明非劣效性（单侧 α 值为 0.025，效力≥90%，非劣效性边界为 0.10）。次要结局包括输血、与出血相关的临床结局、凝血参数和安全性。
该试验已获得所有参与中心的机构审查委员会的批准。预计试验将于 2024 年底完成，结果将通过发表在同行评议期刊上的文章和 2025 年的会议报告进行传播。研究结果将有助于我们更好地了解出血手术患者的凝血管理，可能减少对同种异体血液制品的需求，并改善手术患者的结局。
NCT05523297。
