NCT05156983招募中3 期
A Phase 3, Prospective, Randomized, Open-label, Adaptive Group Sequential, Multicenter Trial With Blinded Endpoint Assessment to Evaluate the Efficacy and Safety of TAK-330 for the Reversal of Direct Oral Factor Xa Inhibitor-induced Anticoagulation in Patients Requiring Urgent Surgery/Invasive Procedure
Takeda109 个研究点 分布在 13 个国家目标入组 440 人开始时间: 2022年8月24日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 440
- 试验地点
- 109
- 主要终点
- Percentage of Participants With Intraoperative Effective Hemostasis
研究概览
简要总结
The aim of this study is to find out the effects of TAK-330 compared with four-factor prothrombin complex concentrate (4F-PCC) as part of standard treatment other than Prothromplex Total for anticoagulation reversal in participants treated with Factor Xa inhibitors who require urgent surgery/invasive procedure.
The participant will be assigned by chance to either TAK-330 or SOC 4F-PCC as part of standard treatment before surgery.
Patients participating in this study will need to be hospitalized. They will also be contacted (via telehealth/phone call) 30 days after the surgery.
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)
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
- •Participant or legally authorized representative willing to sign e-consent/written informed consent form.
- •Participants at least 18 years of age at enrollment.
- •Participant currently on treatment with oral Factor Xa inhibitor (rivaroxaban, apixaban, edoxaban).
- •In the opinion of the surgeon, the participant requires an urgent surgery/procedure that is associated with high-risk of intraoperative bleeding within 15 hours from the last dose of Factor Xa inhibitor and requires a reversal agent for suspected direct oral Factor Xa inhibitor-related coagulopathy. For participants who are beyond the 15-hour window, eligibility requires proof of elevated plasma anti-Factor Xa (FXa) levels using either specific direct oral anti-coagulant (DOAC)-calibrated (apixaban, rivaroxaban or edoxaban) anti-FXa levels of greater than (>) 75 nanograms per milliliter (ng/mL), or heparin calibrated anti-FXa assay levels of >0.5 international unit per milliliter (IU/mL) at screening.
- •Women of childbearing potential should have a negative pregnancy test documented prior to enrollment.
排除标准
- •The participant has an expected survival of less than 30 days, even with best available medical and surgical care.
- •Recent history (within 90 days prior to screening) of venous thromboembolism, myocardial infarction (MI), disseminated intravascular coagulation (DIC), ischemic stroke, transient ischemic attack, hospitalization for unstable angina pectoris or severe or critical coronavirus 2 (SARS-CoV-2) infection.
- •Active major bleeding defined as bleeding that requires surgery or transfusion of >2 units of packed red blood cell (PRBC) or intracranial hemorrhage with the exception of subacute and chronic subdural hemorrhages with a Glasgow Coma Score (GCS) greater than or equal to (>=)
- •Polytrauma for which reversal of Factor Xa-inhibition alone would not be sufficient to achieve hemostasis.
- •Known prothrombotic disorder including primary antiphospholipid syndrome, antithrombin-3 deficiency, homozygous protein C deficiency, homozygous protein S deficiency, and homozygous factor V Leiden.
- •Known bleeding disorder (example, platelet function disorders, hemophilia, Von Willebrand disease, or coagulation factor deficiency).
- •Platelet count less than (<) 50,000 per microliter (/mcL).
- •History of heparin-induced thrombocytopenia.
- •Administration of procoagulant drugs (example, non-study prothrombin complex concentrates (PCCs), recombinant Factor VIIa) or blood products (transfusion of whole blood, fresh frozen plasma, cryoglobulins, plasma fractions, or platelets) within 7 days before enrollment. (Note: administration of PRBCs for hemoglobin correction, tranexamic acid or aminocaproic acid are not exclusion criteria).
- •Planned use of procoagulant drugs (example, Vitamin K, non-study PCCs, recombinant Factor VIIa) or blood products (transfusion of whole blood, fresh frozen plasma, cryoglobulins, plasma fractions, or platelets) after enrollment but before the 24±4 hours hemostatic assessment (Key secondary endpoint). Planned administration of tranexamic acid (TXA) or aminocaproic acid after randomization but before the start of IP infusion, should be noted during randomization to properly stratify these participants in the interactive response technology (IRT). Planned administration of TXA or aminocaproic acid after start of IP infusion but before the 24±4 hours hemostatic assessment is prohibited. Administration of any of the above products before the 24±4 hours hemostatic assessment will impact the assessment of hemostasis. Administration of PRBCs for hemoglobin correction, is not an exclusion criterion.
- •Administration of unfractionated heparin within 2 hours before randomization or low molecular weight heparin within 6 hours before randomization.
- •Hypersensitivity to PCC constituents or any excipient of TAK-
- •Participants with history of confirmed immunoglobulin A (IgA) deficiency with hypersensitivity reaction and antibodies to IgA.
- •Septic shock as defined by persistent hypotension requiring vasopressors to maintain mean arterial pressure (MAP) >=65 millimeters of mercury (mmHg) and having blood lactate >2 millimole (mmol) despite adequate volume resuscitation.
- •Acute or chronic liver failure (hepatic cirrhosis Child-PUGH score C)
- •Renal failure requiring dialysis
- •Any other condition that could, in the opinion of the investigator, put the participant at undue risk of harm if the participant were to participate in the study.
- •Participation in another clinical study involving an investigational product or device within 30 days prior to study enrollment, or planned participation in another clinical study involving an investigational product or device during the course of this study. Participation in an observational study is not an exclusion criterion.
- •The use of PROTHROMPLEX TOTAL as SOC 4F-PCC.
- •Women who are breastfeeding at the time of enrollment.
研究组 & 干预措施
TAK-330 25 IU/kg
Experimental
Participants will receive TAK-330, 25 international unit per kilogram (IU/kg) single intravenous infusion on Day 1 (prior to surgery) as an initial dose and an additional dose of 25 IU/kg TAK-330 can be administered during the surgery if deemed necessary by the surgeon. The total dose of TAK-330 administered to the participant should not exceed 50 IU/kg or 5,000 IU, whichever is smaller.
干预措施: TAK-330 (Drug)
SOC 4F-PCC
Active Comparator
Participants will receive 4F-PCC (excluding Prothromplex Total and activated 4F-PCC) as standard of care (SOC) on Day 1 (prior to surgery). The dose and infusion speed of the SOC 4F-PCC will be based on local institutional protocols. An additional dose of SOC 4F-PCC not exceeding total dose of 50 IU/kg or 5,000 IU, whichever is smaller can be given during the surgery if required.
干预措施: SOC 4F-PCC (Drug)
结局指标
主要结局
Percentage of Participants With Intraoperative Effective Hemostasis
时间窗: At the end of the surgery/procedure
Percentage of participants achieving intraoperative effective hemostasis, as determined by the Intraoperative Four Point Hemostatic Efficacy Scale and assessed by the principal investigator (PI), the surgeon, or a qualified member of the surgical team.
次要结局
- Number of Units of Packed Red Blood Cells (PRBCs) Administered to Achieve Bleeding Control(Within 24 hours after the end of investigational product infusion)
- Percentage of Participants With Postoperative Effective Hemostasis(At 24 hours after the end of investigational product infusion)
- Number of Participants With Usage of Blood Products or Non-Study Hemostatic Agents for Bleeding Control(Within 24 hours after the end of investigational product infusion)
- Percentage of Participants With Intraoperative Effective Hemostasis Based on Hemostatic Efficacy Rating Algorithm(At the end of the surgery/procedure)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interests (AESIs)(Within 30 days after the end of the surgery/invasive procedure (up to 33 days))
- Number of Participants With Thrombotic Events(Within 30 days after the end of the surgery/invasive procedure (up to 33 days))
- Number of Participants With Deaths Within 30 Days Post-Surgery/Invasive Procedure(Within 30 days post-surgery/invasive procedure (up to 33 days))
研究者
研究点 (109)
Loading locations...
相似试验
已完成
2 期
A Phase 2 Efficacy and Safety Study of TAK-063 in Participants With an Acute Exacerbation of SchizophreniaSchizophreniaNCT02477020Takeda164
已完成
3 期
A Study to Investigate the Procoagulant Effect of Tenecteplase (TNK-tPA), Alteplase (Rt-PA) and Streptokinase (SK) Administered to Patients With Acute Myocardial Infarction (AMI)Myocardial InfarctionNCT02182011Boehringer Ingelheim49
已完成
2 期
Safety and Efficacy of TAK-385 for Patients With Localized Prostate CancerProstate CancerNCT02135445Millennium Pharmaceuticals, Inc.103
已完成
2 期
A Phase 2 Study to Evaluate the Safety and Efficacy of TAK-385, Together With a Leuprorelin Observational Cohort, in Participants With Prostate CancerProstate CancerNCT02083185Millennium Pharmaceuticals, Inc.136
已完成
1 期
Safety, Tolerability and Pharmacokinetic Study of Multiple Rising Doses of TAK- 063 in Participants With Stable Schizophrenia and Healthy ParticipantsSchizophreniaNCT01879722Takeda77