Effectiveness of Different Fibrinogen Preparations in Restoring Clot Firmness
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- FIBTEM MCF (mm)
研究概览
简要总结
Fibrinogen concentrate is produced by different manufacturers using different purification technologies. The products available in Italy are three: RiaSTAP (CSL Behring), FIBRYGA (Octapharma), and FibCLOT (LFB). RiaSTAP and FIBRYGA are sold in 1-gram vials, and FibCLOT - in 1.5-gram vials. A recent in vitro study assessed how these products affected the clot firmness measured by the ROTEM FIBTEM maximum clot firmness (MCF) parameter. In vitro conditions, FibCLOT was verified to be the most efficient in increasing clot firmness.
The present study is aimed to assess, in a series of patients undergoing cardiac surgery with cardiopulmonary bypass, the hypothesis that the FibCLOT fibrinogen is superior to the RiaSTAP fibrinogen in increasing the FIBTEM MCF parameter in a clinical model of bleeding (postoperative bleeding after complex cardiac surgery).
详细描述
The Effectiveness of DIfferent fibrinogen PreparatiOns in Restoring clot firmness (EDIPO RE) is a pragmatic, double-blinded, randomized controlled trial testing the hypothesis that FibCLOT is superior to RiaSTAP in restoring fibrinogen-dependent clot firmness in cardiac surgery acquired hypofibrinogenemia.
A randomization sequence was generated by a computerized system, and then sealed envelopes containing the drug assigned were prepared. The randomization ratio of the treatment arms was 1:1. An unblinded biologist was in charge of running the ROTEM® tests, randomization, drug preparation, and masking, and its delivery to the operating room. The attending anesthesiologist, the surgical staff, and the medical staff in the ICU and ward were blinded.
After protamine administration, if microvascular bleeding was observed or suspected, POC testing, including ROTEM® EXTEM and FIBTEM, was run. If FIBTEM MCF was lower than 10 mm, the patient was randomly allocated to receive a dose of RiaSTAP® or FibCLOT® of 30 mg/kg, approximated to the closest between 2 or 3 grams. If no sign of ongoing bleeding was present, or FIBTEM MCF was 10 mm or higher the patient was considered screen failure and excluded from further observation.
Forty patients were randomized to receive the assigned treatment.
Fibrinogen was administrated intravenously by infusion at a rate of approximately 20 ml/min. Ten minutes after fibrinogen administration a second test was performed with ROTEM® EXTEM and FIBTEM tests to record the change of the parameters due to fibrinogen supplementation. No other hemostatic drugs nor transfusions, outside the study drug, were administered between the first and the second testing. In case of ongoing intra- or postoperative bleeding, after the second testing, all the hemostatic corrections were allowed and guaranteed by our institutional protocol for postoperative bleeding management, which includes the following step-by-step interventions:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
A computerized system generated a randomization sequence, and then sealed envelopes containing the drug assigned was prepared. The randomization ratio of the treatment arms was 1:1. An unblinded biologist (E.B.) was in charge of running the ROTEM® tests, randomization, drug preparation, and masking, and its delivery to the operating room. The attending anesthesiologist, the surgical staff, and the medical staff in the ICU and ward were blinded.
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
- •elective cardiac surgery with cardiopulmonary bypass;
- •complex cardiac surgery (coronary artery bypass graft + valve repair/replacement; double/triple valve repair/replacement; ascendant aorta surgery);
- •written consent to participate;
排除标准
- •urgent or emergent cardiac surgery;
- •known hypersensitivity to the active principle or to one of the excipients of the study drugs;
- •coagulation disorders, known or presumable from anamnesis;
- •known hepatopathy;
- •known risk of thrombosis or disseminated intravascular coagulation;
- •participation in another clinical study where an experimental product has been administered within 30 days from the day of the inclusion in the study;
- •whatever clinical condition that, in the opinion of the investigator, makes the patients not suitable to the experimentation.
研究组 & 干预措施
FibCLOT
Patients randomized to the FibCLOT arm will receive 30 mg/kg, approximated to the closest between 2 and 3 grams, of FibCLOT (LFB, Puteaux, France).
干预措施: FibCLOT (Drug)
RiaSTAP
Patients randomized to the RiaSTAP arm will receive 30 mg/kg, approximated to the closest between 2 and 3 grams, of RiaSTAP (King of Prussia, PA, USA).
干预措施: RiaSTAP (Drug)
结局指标
主要结局
FIBTEM MCF (mm)
时间窗: Within 10 minutes after protamine administration
Fibrinogen contribution to the clot firmness measured by ROTEM device, as maximum clot firmness parameter).
FIBTEM CT and CFT (sec)
时间窗: Within 10 minutes after protamine administration
Fibrinogen contribution to the clot firmness measured by ROTEM device, as time required for clot formation (CT, clotting time, and CFT, clot formation time).
EXTEM CT and CFT (sec)
时间窗: Within 10 minutes after protamine administration
Time required for the overall clot formation on the extrinsic pathway of coagulation ( CT, clotting time, and CFT, clot formation time).
次要结局
- Postoperative bleeding(12 and 24 hours after surgery)
- Incidence of moderate/severe bleeding(12 hours after surgery)
- Incidence of transfusion(12 and 24 hours after surgery)
研究者
Marco Ranucci
Director of the Cardiovascular Anesthesia and Intensive Care Department
IRCCS Policlinico S. Donato