Prospective, Multi-center, Randomized, Parallel-control, Superiority Study Comparing Administration of Clotting Factor Concentrates With a Standard Massive Hemorrhage Protocol in Severely Bleeding Trauma Patients.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 350
- 试验地点
- 11
- 主要终点
- Composite of total number of Allogeneic Blood Products (ABPs)
研究概览
简要总结
Injury is the leading cause of death for people between the ages of 1-44. This is especially true in trauma patients who have bleeding complications. Acute trauma coagulopathy (ATC) is associated with high transfusion requirements, longer ICU stays, and a greater incidence of multi-organ dysfunction. The cause of coagulopathy is multi-factorial.
One major driver is acquired fibrinogen deficiency (hypofibrinogenemia). Fibrinogen is critical in clot formation and enhances platelet aggregation. Due to the body's limited reserve, it is the first clotting factor to fall to critical levels during life-threatening bleeding. This can impair coagulation and increases bleeding complications. There are two primary options available for fibrinogen supplementation:
- Cryoprecipitate- North American standard
- Fibrinogen Concentrate (FC)- European standard
Consumption of coagulation factors, including fibrinogen, is another important component of ATC. To replenish these depleted coagulation factors and improve thrombin generation, two therapies are available:
- Frozen Plasma (FP)- North American standard
- Prothrombin Complex Concentrate (PCC)- European standard
Strategies for hemorrhage and coagulopathy treatment have changed significantly over the last decade. Prompt hemorrhage control, along with targeted coagulation factor replacement, are emerging as key components of trauma care. Currently, the initiation of a massive hemorrhage protocol (MHP) results in red blood cells (RBCs) and FP transfusions in a 1:1 or 2:1 ratio. Clotting factors are replaced via FP administration. Fibrinogen supplementation is administration after lab verification or at the clinician's discretion. MHP continues until the rate of hemorrhage is under control.
FC and PCC have several important advantages over cryoprecipitate and FP but there is a scarcity of data regarding their efficacy and safety of their use in hemorrhaging trauma patients. The FiiRST-2 study aims to understand if early use of FC and PCC in trauma patients at risk of massive hemorrhage will lead to superior patient outcomes. This trial will also provide safety data on early administration of FC and PCC as a first-line hemostatic therapy in trauma care, and its impact on hemostatic and other clinical endpoints.
详细描述
Study Design and Duration FiiRST-2 is a multicenter, randomized, parallel-control, superiority trial, utilizing a conventional two-armed, two-stage design, with an adaptive interim analysis, performed at Level 1 Trauma Centers in Canada. The study is designed to examine the effect of replacing fibrinogen and clotting factors via FC and PCC following activation of the massive hemorrhage protocol (MHP) on the number of ABP units transfused in trauma patients with severe hemorrhage versus the current standard of care (ratio-based plasma resuscitation).
Test Products, Dose, and Mode of Administration:
Patients will be randomized if the MHP is activated according to the MHP activation criteria at each study site. Once eligibility is confirmed, the blood bank medical laboratory technologist will randomize the patient to one of two groups: the intervention group or the control group.
- Intervention group: 4 g Fibryga and 2000 IU Octaplex will be released as part of the first and second MHP packs.
- Control group: 4 U FP will be released as part of the first and second MHP packs.
- Concomitant therapy: In both groups, 4 U RBC will be included as part of the first and second MHP packs, and 1 dose of platelets (4 U of pooled random donor or single donor apheresis) will also be included as part of the second MHP pack. Both RBCs and platelets will be administered according to the clinical situation and/or lab results as per the discretion of the clinical team. The second MHP pack will be released at the request of the clinical team, but clinicians will be instructed to administer all of the investigational product (Fibryga/Octaplex or FP) in the first pack before moving onto the second pack. Similarly, if the second pack is opened, clinicians will be instructed to administer all of the investigational products contained within, before moving to the third pack. Not administering all of the investigational products in the first pack, once started, will be a protocol deviation.
Administration of all non-investigational products will be at the discretion of the clinical team according to the hemodynamic status of the patient and/or laboratory results (standard and/or point-of-care as per institutional practice). While platelets will be routinely included in the second pack, clinicians can request platelets outside of the packs (e.g., for patients on antiplatelet therapy or with marked thrombocytopenia). In the control group, FC may be administered if hypofibrinogenemia (fibrinogen level below 1.5-2.0 g/L or FIBTEM A10 below 8-12 mm) is identified as part of routine testing, at the discretion of the clinical team. Patients in the intervention group can receive additional FC if hypofibrinogenemia (as per above criteria) is identified after the full dose (4g) in the first pack is administered (if the second pack is not opened). If the second pack is opened, additional doses of FC will be permitted after the full dose (4g) in the second pack is administered..
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Given blood products in each randomized arm have different physical differences, it is not possible to blind the treating health care providers to group assignment.
Clinicians not involved in the acute resuscitation period (MHP activations usually last under 4 hours) and outcome assessors will remain blinded by using a generic product label in the patient chart and/or the electronic product name (i.e., FiiRST-2 MHP pack 1 and pack 2, rather than specifying type of product used). The first pack will be sealed, and the treating health care providers will be instructed to refrain from opening the first pack until the decision is made to transfuse clotting factor replacement.
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Severely injured adult trauma patients who meet all following criteria:
- •Estimated age greater than 16 years old
- •Severely injured (penetrating or blunt) trauma patients
- •Triggered MHP within first hour of hospital arrival at the trauma bay/ED
排除标准
- •Patients who meet any of the following criteria are not eligible for the study:
- •Have received more than 2 U RBCs during the pre-hospital phase of care
- •Have received more than 2 U RBCs in the trauma bay/ED before activation of the MHP
- •Have an elapsed time from injury of more than 3 hours
- •Have a penetrating traumatic brain injury with Glasgow Coma Scale (GCS) of 3
- •Are suspected or known to be on anticoagulants in the last 7 days
- •Have known congenital or acquired bleeding disorders
- •Have a known pregnancy
- •Refuse blood transfusion due to religion or other reasons
- •Previous history of heparin induced thrombocytopenia (HIT)
结局指标
主要结局
Composite of total number of Allogeneic Blood Products (ABPs)
时间窗: within 24 hours
The primary endpoint is to demonstrate superiority with respect to the composite number of all ABP units (RBCs, FP and platelets) transfused
次要结局
- Incidence of thromboembolic events(up to 28 days)
- Ventilator-free days(From arrival to day 28)
- Total number of RBC units(Transfused within the 24 hours)