A Randomized, Active-controlled, Multicenter, Phase III Study Investigating Efficacy and Safety of Intra-operative Use of BT524 (Human Fibrinogen Concentrate) in Subjects Undergoing Major Spinal or Abdominal Surgery (AdFIrst)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Biotest
- 入组人数
- 222
- 试验地点
- 19
- 主要终点
- Intra-operative Blood Loss
研究概览
简要总结
The main purpose of this study was to demonstrate the efficacy and safety of intraoperative use of fibrinogen concentrate BT524, as a complementary therapy for the management of uncontrolled severe hemorrhage in acquired hypofibrinogenemia. This non-inferiority study focused on the primary objective of demonstrating that BT524 is non-inferior that means not worse than the comparator fresh frozen plasma/cryoprecipitate in reducing intraoperative blood loss when administered intravenously in subjects with acquired hypofibrinogenemia undergoing elective major spinal or abdominal surgery.
详细描述
Fibrinogen is the first coagulation factor to become critically reduced during intraoperative bleeding. Therefore, rapid supplementation of fibrinogen to restore physiological plasma levels is an important component in achieving and maintaining hemostasis in bleeding patients. In this study, subjects with major blood loss during elective spinal surgery or abdominal surgery were randomized to receive either intravenous transfusion of the fibrinogen concentrate BT524, or fibrinogen-containing fresh frozen plasma/cryoprecipitate as first hemostatic intervention to rapidly replenish fibrinogen and control bleeding.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
Study 995 was partially blinded; surgeon, surgical staff and subjects were blinded to treatment allocation throughout the entire surgery. The subject was blinded throughout the study. The Investigational Medicinal Product (IMP), BT524 or FFP/Cryo, was administered by an unblinded anaesthesiologist.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At screening:
- •Written informed consent
- •Subjects scheduled for elective major spinal surgery or cytoreductive pseudomyxoma peritonei (PMP) surgery with expected major blood loss
- •Male or female, aged ≥ 18 years
- •No increased bleeding risk as assessed by standard coagulation tests and medical history
- •Intra-operative:
- •Subjects who underwent spinal surgery: Intra-operative clinically relevant bleeding of approximately 1 Liter, requiring hemostatic treatment during surgery.
- •Subjects who underwent cytoreductive PMP surgery: Intra-operative prediction of clinically relevant bleeding of more than 2 Liter, requiring hemostatic treatment during surgery
排除标准
- •Pregnancy or unreliable contraceptive measures or breast feeding (women only)
- •Hypersensitivity to proteins of human origin or known hypersensitivity reactions to components of the Investigational Medicinal Products (IMP)
- •Participation in another clinical study within 30 days before entering the study or during the study and/or previous participation in this study
- •Treatment with any fibrinogen concentrate and/or fibrinogen-containing product within 30 days prior to infusion of IMP
- •Employee or direct relative of an employee of the Contract Research Organization (CRO), the study site, or Biotest
- •Inability or lacking motivation to participate in the study
- •Medical condition, laboratory finding (e.g., clinically relevant biochemical or hematological findings outside the normal range), or physical exam finding that in the opinion of the investigator precludes participation
- •Presence or history of venous/arterial thrombosis or thromboembolic event (TEE) in the preceding 6 months
研究组 & 干预措施
BT524
Investigational Human Fibrinogen Concentrate
干预措施: BT524 (Biological)
Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo)
Standard of Care
干预措施: FFP/Cryo (Biological)
结局指标
主要结局
Intra-operative Blood Loss
时间窗: From decision to treat the subject with IMP until end of surgery, an average of 5 hours
Intra-operative blood loss as measured by amount of blood from blood suction unit and amount of blood from surgical cloths and compresses.
次要结局
- Proportion (%) of Subjects With Successful Correction of Fibrinogen Level (FIBTEM A10) 15 Minutes After Start of First IMP Administration(Prior first dose, 15 minutes after start of first IMP administration)
- Time to First Successful Correction of Fibrinogen Level(prior 1st dose, pre-dose, 15 minutes and 90 minutes after start of first IMP administration, end of surgery)
- Transfusion Requirements: Cell Salvage(After start of first IMP administration until end of surgery, an average of 5 hours)
- Transfusion Requirements: Allogeneic Platelets(After start of first IMP administration until end of surgery, an average of 5 hours)
- Transfusion Requirements: Allogeneic Red Blood Cells(After start of first IMP administration until end of surgery, an average of 5 hours)
- Transfusion Requirements: Fresh Frozen Plasma(After start of first IMP administration until end of surgery, an average of 5 hours)
- Transfusion Requirements, Cryoprecipitate(After start of first IMP administration until end of surgery, an average of 5 hours)
- Amount of Red Blood Cells (RBCs)(After start of first IMP administration until end of surgery, an average of 5 hours)
- Post-operative Blood Loss(From end of surgery (time of last suture) up to 24 hours after the end of surgery)
- Subjects With Rebleeds(End of surgery up to 8 days after surgery)
- Hospital Length of Stay After Surgery(From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days))
- In-hospital Mortality(From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days))
- Number of Subjects With Thrombosis or Thromboembolic Events (TEEs)(From day of surgery until closing visit (up to 181 days))
- Change in Viral Status(Screening visit (up to 42 days prior to surgery) and closing visit (up to 181 days after surgery))