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Efficacy and Safety of Bivalirudin Versus Heparin During Coil Embolization in Patients With Ruptured Intracranial Aneurysms (BUILD)

Primary Purpose

Subarachnoid Hemorrhage, Aneurysmal

Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Bivalirudin 250 MG Injection
Heparin
Sponsored by
Changhai Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Subarachnoid Hemorrhage, Aneurysmal focused on measuring Anticoagulant Agents, Aneurysm, Intracranial Berry, Therapeutic Embolization, Anticoagulation Agents, Heparin Sodium, Bivalirudin

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Aged 18 to 80 years, any gender
  • intracranial aneurysms ruptured in 14 days
  • Diagnosed as subarachnoid hemorrhage (SAH) by CT, confirmed aneurysmal SAH by DSA
  • Hunt-Hess I-III
  • Patient is suitable for coil embolization
  • Informed consent and availability of the subject for the entire study period and willingness of the subject to adhere to protocol requirements

Exclusion Criteria:

  • Nonsaccular Aneurysms (include infective, fusiform, dissecting aneurysms)
  • Prior intracranial aneurysms
  • Poor baseline of mRS 4-5
  • Aneurysms that cannot be successfully treated by interventional treatment judged by clinician.
  • Patients cannot receive antiplatelet aggregation or anticoagulant therapy
  • Patients with indications for emergency craniotomy: intracranial hematoma, high intracranial pressure or hydrocephalus etc..
  • Patients with AVM, intracranial artery stenosis or moyamoya disease
  • Pregnancy or lactation
  • Patients with severe abnormal function of main organs, liver or kidney
  • Other serious diseases not suitable for this study
  • Patients are currently participating in another drug-related clinical study
  • Patients are allergic to heparin or bivalirudin and its excipients or hirudin
  • Patients with a clear history of allergy to coil embolic material
  • Patients had or may have had severe reactions to contrast media that could not complete the preoperative medication
  • Patients are not suitable to participate in this clinical study judged by clinician

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Bivalirudin

    Heparin

    Arm Description

    Bivalirudin at full dose Bivalirudin 0.75 mg/kg intravenous bolus loading dose, and immediately followed by intravenous infusion of 1.75 mg/kg/h until end of the procedure

    Heparin first dose at 0.6mg/kg(75U/kg) Heparin should be administered each hour, 0.6mg/kg(75U/kg) as bolus dose, 0.3mg/kg 1h later, 10mg(1250U) every hour after.

    Outcomes

    Primary Outcome Measures

    Procedure-related complication
    A composite of of death from any cause, thromboembolic events, or bleeding defined by BARC definition 3 or 5 BARC=Bleeding Academic Research Consortium

    Secondary Outcome Measures

    Modified Rankin Scale (mRS)
    The mRS score, and proportion of subjects achieving mRS score of 0-2
    Activated Clotting Time (ACT)
    ACT values of 0 min and 5 min after bolus injection will be recorded in all patients Extra ACT values of 15 min, 30 min, 55min, 65 min,and 115 min after bolus injection will be recorded in 8 patients of both arm, and the curve will be simulated
    Procedure-related complication
    A composite of of death from any cause, thromboembolic events, or bleeding defined by BARC definition 3 or 5 BARC=Bleeding Academic Research Consortium
    Thromboembolic events
    Definition: Intraoperative: stent thrombosis/stenosis, distal vascular occlusion on imaging Postoperative： 1) new deficits or change in level of consciousness, intracranial hemorrhage cause is excluded by CT, 2) no clinical symptom but CT showed new infarction
    Bleeding events
    Any bleeding as defined by the BARC definition (except grade 4) Any bleeding as defined by the GUSTO definition
    Intracranial hemorrhage
    Intracranial hemorrhage and Symptomatic intracranial hemorrhage
    Heparin-induced thrombocytopenia(HIT)
    defined as a platelet count decrease ofmore than50%or more than 150 × 109/L frombaseline

    Full Information

    First Posted
    August 26, 2020
    Last Updated
    August 26, 2020
    Sponsor
    Changhai Hospital
    Collaborators
    The First Affiliated Hospital of Zhengzhou University, Zhejiang University, Wuhan University, Qilu Hospital of Shandong University, The First People's Hospital of Changzhou
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04532333
    Brief Title
    Efficacy and Safety of Bivalirudin Versus Heparin During Coil Embolization in Patients With Ruptured Intracranial Aneurysms
    Acronym
    BUILD
    Official Title
    Anticoagulant Efficacy and Safety of BivalirUdin Versus heparIn During coiL Embolization in Patients With ruptureD Intracranial Aneurysms: an Open-label, Multicenter, Randomized Pilot Study（BUILD）
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    August 2020 (Anticipated)
    Primary Completion Date
    May 2021 (Anticipated)
    Study Completion Date
    June 2021 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Changhai Hospital
    Collaborators
    The First Affiliated Hospital of Zhengzhou University, Zhejiang University, Wuhan University, Qilu Hospital of Shandong University, The First People's Hospital of Changzhou

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a randomized, open label, multi-center, positive-controlled study, in which a total of 236 patients will be enrolled and randomly assigned to receive bivalirudin or heparin in a 1:1 ratio during coil embolization in patients with ruptured intracranial aneurysms. Procedure-related complication, mRS, Activated Clotting Time, ischemic and hemorrhagic complications, symptomatic and asymptomatic intracranial hemorrhage, death, Heparin Induced Thrombocytopenia will be evaluated during procedure, at 24hs, 7days and 30 days after.
    Detailed Description
    Endovascular embolization has become an effective modality for the treatment of intracranial aneurysms. Despite advances in technology and techniques, thromboembolic and bleeding events are still encountered as inherent perioperative complications. Hypercoagulability as a systemic response to acute subarachnoid hemorrhage (SAH) may be associated with an increased incidence of thromboembolic events. The administration of anticoagulant may reduce thromboembolic events during the endovascular embolization, meanwhile, involves the risk of bleeding. Although heparin is commonly used during the procedure, the safety in patients with ruptured intracranial aneurysms has not been established. In contrast to heparin, bivalirudin is a short-lived direct thrombin inhibitor with an intrinsic antiplatelet activity and more stable pharmacokinetic and pharmacodynamic properties which has been associated with reduced bleeding and an overall favorable profile. Bivalirudin administration in patients with high bleeding risk during coronary intervention is recommended by current guidelines. This is an open label, multicenter, randomized pilot study, which is aimed to investigate the safety and efficacy of bivalirudin coil embolization in patients with ruptured intracranial aneurysms.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Subarachnoid Hemorrhage, Aneurysmal
    Keywords
    Anticoagulant Agents, Aneurysm, Intracranial Berry, Therapeutic Embolization, Anticoagulation Agents, Heparin Sodium, Bivalirudin

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    236 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Bivalirudin
    Arm Type
    Experimental
    Arm Description
    Bivalirudin at full dose Bivalirudin 0.75 mg/kg intravenous bolus loading dose, and immediately followed by intravenous infusion of 1.75 mg/kg/h until end of the procedure
    Arm Title
    Heparin
    Arm Type
    Active Comparator
    Arm Description
    Heparin first dose at 0.6mg/kg(75U/kg) Heparin should be administered each hour, 0.6mg/kg(75U/kg) as bolus dose, 0.3mg/kg 1h later, 10mg(1250U) every hour after.
    Intervention Type
    Drug
    Intervention Name(s)
    Bivalirudin 250 MG Injection
    Intervention Description
    Bivalirudin 0.75 mg/kg intravenous bolus loading dose, and immediately followed by intravenous infusion of 1.75 mg/kg/h until end of the procedure
    Intervention Type
    Drug
    Intervention Name(s)
    Heparin
    Intervention Description
    Heparin should be administered each hour, 0.6mg/kg(75U/kg) as bolus dose, 0.3mg/kg 1h later, 10mg(1250U) every hour after.
    Primary Outcome Measure Information:
    Title
    Procedure-related complication
    Description
    A composite of of death from any cause, thromboembolic events, or bleeding defined by BARC definition 3 or 5 BARC=Bleeding Academic Research Consortium
    Time Frame
    30 days
    Secondary Outcome Measure Information:
    Title
    Modified Rankin Scale (mRS)
    Description
    The mRS score, and proportion of subjects achieving mRS score of 0-2
    Time Frame
    30 days
    Title
    Activated Clotting Time (ACT)
    Description
    ACT values of 0 min and 5 min after bolus injection will be recorded in all patients Extra ACT values of 15 min, 30 min, 55min, 65 min,and 115 min after bolus injection will be recorded in 8 patients of both arm, and the curve will be simulated
    Time Frame
    During procedure
    Title
    Procedure-related complication
    Description
    A composite of of death from any cause, thromboembolic events, or bleeding defined by BARC definition 3 or 5 BARC=Bleeding Academic Research Consortium
    Time Frame
    During procedure, at 24hs, 7days
    Title
    Thromboembolic events
    Description
    Definition: Intraoperative: stent thrombosis/stenosis, distal vascular occlusion on imaging Postoperative： 1) new deficits or change in level of consciousness, intracranial hemorrhage cause is excluded by CT, 2) no clinical symptom but CT showed new infarction
    Time Frame
    During procedure, at 24hs, 7days, 30days
    Title
    Bleeding events
    Description
    Any bleeding as defined by the BARC definition (except grade 4) Any bleeding as defined by the GUSTO definition
    Time Frame
    During procedure, at 24hs, 7days, 30days
    Title
    Intracranial hemorrhage
    Description
    Intracranial hemorrhage and Symptomatic intracranial hemorrhage
    Time Frame
    During procedure, at 24hs, 7days, 30days
    Title
    Heparin-induced thrombocytopenia(HIT)
    Description
    defined as a platelet count decrease ofmore than50%or more than 150 × 109/L frombaseline
    Time Frame
    7days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Aged 18 to 80 years, any gender intracranial aneurysms ruptured in 14 days Diagnosed as subarachnoid hemorrhage (SAH) by CT, confirmed aneurysmal SAH by DSA Hunt-Hess I-III Patient is suitable for coil embolization Informed consent and availability of the subject for the entire study period and willingness of the subject to adhere to protocol requirements Exclusion Criteria: Nonsaccular Aneurysms (include infective, fusiform, dissecting aneurysms) Prior intracranial aneurysms Poor baseline of mRS 4-5 Aneurysms that cannot be successfully treated by interventional treatment judged by clinician. Patients cannot receive antiplatelet aggregation or anticoagulant therapy Patients with indications for emergency craniotomy: intracranial hematoma, high intracranial pressure or hydrocephalus etc.. Patients with AVM, intracranial artery stenosis or moyamoya disease Pregnancy or lactation Patients with severe abnormal function of main organs, liver or kidney Other serious diseases not suitable for this study Patients are currently participating in another drug-related clinical study Patients are allergic to heparin or bivalirudin and its excipients or hirudin Patients with a clear history of allergy to coil embolic material Patients had or may have had severe reactions to contrast media that could not complete the preoperative medication Patients are not suitable to participate in this clinical study judged by clinician
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Rui Zhao, Doctor
    Phone
    +86-13916728169
    Email
    z_ray1979@126.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Qiao Zuo, Doctor
    Phone
    +86-13621817430
    Email
    dr_zuo@126.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jianmin Liu, M.D.
    Organizational Affiliation
    Neurosurgical Department of Changhai Hospital
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Sheng Guan, M.D.
    Organizational Affiliation
    Neurointerventional Department, The First Affiliated Hospital of Zhengzhou University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    Efficacy and Safety of Bivalirudin Versus Heparin During Coil Embolization in Patients With Ruptured Intracranial Aneurysms

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