Prospective, Multicenter, Active-control Randomized Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Bleeding Adult Cardiac Surgical Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Octapharma
- 入组人数
- 420
- 试验地点
- 13
- 主要终点
- Number of Patients Requiring Additional Hemostatic Intervention
研究概览
简要总结
This is a multicenter, active-control randomized, prospective, Phase 3 study in adult cardiac surgery patients. 420 patients were randomized at 12 hospitals.
详细描述
Patients were randomized to receive either 4-factor PCC (Octaplex) or frozen plasma (FP). The study compared the hemostatic treatment response to Octaplex versus FP, defined as effective if no additional systemic or surgical hemostatic intervention is required from 60 minutes to 24 hours after initiation of the first treatment dose. The study includes adult (≥18 years old) patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) and required coagulation factor replacement due to bleeding post-CPB and after adequate reversal of heparin with protamine (as assessed by the surgical staff based on clinical and laboratory criteria) during surgery, and who have a known (e.g., as indicated by INR) or suspected coagulation factor deficiency.
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
- Double (Participant, Outcomes Assessor)
盲法说明
Given the physical differences in the products and the emergency nature of the intervention, attending clinicians present during the infusion of the blood products/components were not blinded to the treatment. To minimize bias, treating clinicians were blinded to group assignments until immediately prior to IMP infusion. The sponsor and data management teams were also blinded to treatment group allocations
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
- •Adult (≥18 years old) patients undergoing any index cardiac surgery employing CPB
- •Coagulation factor replacement with PCC or FP ordered in the operating room for:
- •Management of bleeding, or
- •Anticipated bleeding in a patient who has been on-pump for >2 hours or has undergone a complex procedure (e.g., aortocoronary bypass [ACB] plus aortic valve replacement)
- •Coagulation factor deficiency, either known to exist (e.g., as indicated by elevated EXTEM clotting time [CT] or INR) or suspected based on the clinical situation
- •Patients who have given written informed consent. In United States patients will provide informed consent prior to surgery. In Canada, informed consent will be obtained after surgery, in accordance with Article 3.7A of the 2018 Tri- Council Policy Statement on the Ethical Conduct for Research Involving Humans.
排除标准
- •Undergoing heart transplantation, insertion or removal of ventricular assist devices (not including intra-aortic balloon pump [IABP]) or repair of thoracoabdominal aneurysm
- •Critical state immediately before surgery with high probability of death within 24 hours of surgery (e.g., acute aortic dissection, cardiac arrest within 24 hours before surgery)
- •Severe right heart failure (clinical diagnosis ± echocardiography)
- •Known contraindications to heparin
- •PCC required for reversal of warfarin or direct oral anticoagulant (DOAC; dabigatran, rivaroxaban, apixaban or edoxaban) within 3 days prior to or during surgery
- •Known thromboembolic event (TEE) within 3 months prior to surgery
- •History of severe allergic reactions to PCC or FP
- •Individuals who have immunoglobulin A (IgA) deficiency with known antibodies against IgA
- •Refusal of allogeneic blood products
- •Known pregnancy
- •Currently enrolled in other interventional clinical trials
研究组 & 干预措施
Octaplex
Participants were administered Octaplex according to a recommended initial dose of 1,500 IU for patients weighing ≤60 kg and 2,000 IU for patients weighing >60 kg. A second dose of IMP could be administered if the patient continued to have at least moderate bleeding and suspected coagulation deficiency (e.g., INR ≥1.5) after completion of the first dose, up to the maximum allowable dose (3,000 IU if ≤60 kg or 4,000 IU if >60 kg).
Octaplex: Prothrombin complex concentrate
干预措施: Octaplex (Drug)
Frozen plasma
Participants were administered FP according to a recommended initial dose of 3 U for patients weighing ≤60 kg and 4 U for patients weighing >60 kg. A second dose of IMP could be administered if the patient continued to have at least moderate bleeding and suspected coagulation deficiency (e.g., INR ≥1.5) after completion of the first dose, up to the maximum allowable dose (6 U if ≤60 kg or 8 U if >60 kg).
Frozen Plasma Product, Human
干预措施: Frozen Plasma Product, Human (Drug)
结局指标
主要结局
Number of Patients Requiring Additional Hemostatic Intervention
时间窗: 60 minutes to 24 hours after first dose of IMP
Defined as 'effective' if no additional hemostatic intervention, such as administration of any systemic hemostatic agents (including platelets, cryoprecipitate, fibrinogen concentrate, activated recombinant factor VII \[rFVIIa\], other coagulation factor products or a second dose of IMP) or any hemostatic interventions (including surgical re-opening for bleeding) is required from 60 minutes to 24 hours after initiation of the first dose of IMP.
次要结局
- Comparison of Global Hemostatic Response Based on Requirement of Additional Hemostatic Intervention and Decreased Hemoglobin Levels(60 minutes to 24 hours after first dose of IMP)
- Compare the Amount of Chest Tube Drainage Between the Octaplex and FP Groups.(12 and 24 hours after chest closure)
- Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB).(24 hours after surgery start, after the end of CPB and after IMP initiation)
- Compare Efficacy in Terms of the Mean Number of Total Allogeneic Blood Products (ABPs) (IMP and Non-IMP) Transfused Between the Octaplex and FP Groups.(First 24 hours after the end of CPB)
- Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Products Transfused Between the Octaplex and FP Groups.(First 24 hours after the end of CPB)
- Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Components Transfused Between the Octaplex and FP Groups.(First 24 hours and 7 days after IMP initiation)
- Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups.(24 hours and 7 days after start of surgery, and after the end of CPB and after IMP initiation)
- Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups.(24 hours and 7 days after start of surgery and after the end of CPB and after IMP initiation)
- Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups(24 hours and 7 days after the start of surgery, after the end of CPB and after IMP initiation)
- Compare Incidence of Intracerebral Hemorrhage Between the Octaplex and FP Groups(24 hours after start of surgery, after the end of CPB and after IMP initiation)
- Compare Incidence of Gastrointestinal Hemorrhage Between Octaplex and FP Groups(24 hours after start of surgery, after the end of CPB and after IMP initiation)
- Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups(24 hours after start of surgery, after the end of CPB and after IMP initiation)
- Comparison of the Effect of Octaplex Versus FP Administration on the Change in International Normalised Ratio (INR) Before and After Therapy Administration.(Within 30 minutes before to 60 minutes after the initiation of IMP administration.)
- Comparison of the Effect of Octaplex Versus FP Administration on the Change in Prothrombin Time (PT)(Within 75 minutes before to within 75 minutes after the initiation of IMP administration)
- Comparison of the Effect of Octaplex Versus FP Administration on the Change in Activated Partial Thromboplastin Time (aPTT)(Within 75 minutes before to within 75 minutes after the initiation of IMP administration)
- Comparison of the Effect of Octaplex Versus FP Administration on the Change in Fibrinogen Activity(Within 75 minutes before to within 75 minutes after the initiation of IMP administration)
- Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM EXTEM CT(Within 75 minutes before to within 75 minutes after the initiation of IMP administration)
- Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM EXTEM MCF(Within 75 minutes before to within 75 minutes after the initiation of IMP administration)
- Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM FIBTEM MCF(Within 75 minutes before to within 75 minutes after the initiation of IMP administration)
- Comparison of the Effect of Octaplex Versus FP Administration on the Change in Platelet Count Measured by Plateletworks(Within 75 minutes before to within 75 minutes after the initiation of IMP administration)
- Comparison of the Effect of Octaplex Versus FP Administration on the Change in Platelet Function Measured by Plateletworks(Within 75 minutes before to within 75 minutes after the initiation of IMP administration)
- Comparison of Total Time Elapsed From Initiation of the First Dose of IMP to Arrival Into the ICU Between the Octaplex and FP Groups.(From initiation of IMP to arrival at ICU room (within 24 hours))
- Comparison of Incidence of Serious Treatment-emergent Adverse Events Between Octaplex and FP Groups(From the beginning of surgery up to postoperative day 30)
- Comparison of the Duration of Mechanical Ventilation Between Octaplex and FP Groups(From the beginning of surgery up to postoperative day 30)
- Comparison of the Duration of ICU Stay Between Octaplex and FP Groups(From the beginning of surgery up to postoperative day 30)
- Comparison of the Duration of Hospitalization Between Octaplex and FP Groups(From the beginning of surgery up to postoperative day 30)
- Comparison of the Incidence of Death Between Octaplex and FP Groups(Up to 30 days after the end of CPB)
- Comparison of the Number of Days Alive and Out of Hospital Between Octaplex and FP Groups(From the beginning of surgery up to postoperative day 30)