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

Sponsor

Changhai Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT04532333

Collaborator

The First Affiliated Hospital of Zhengzhou University (Other), Zhejiang University (Other), Wuhan University (Other), Qilu Hospital of Shandong University (Other), The First People's Hospital of Changzhou (Other)

236

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Subarachnoid Hemorrhage, Aneurysmal	Drug: Bivalirudin 250 MG Injection Drug: Heparin	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

236 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

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）

Anticipated Study Start Date :

Aug 1, 2020

Anticipated Primary Completion Date :

May 1, 2021

Anticipated Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bivalirudin 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	Drug: Bivalirudin 250 MG Injection 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
Active Comparator: Heparin 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.	Drug: Heparin Heparin should be administered each hour, 0.6mg/kg(75U/kg) as bolus dose, 0.3mg/kg 1h later, 10mg(1250U) every hour after.

Arm

Intervention/Treatment

Experimental: Bivalirudin

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

Drug: Bivalirudin 250 MG Injection

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

Active Comparator: Heparin

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.

Drug: Heparin

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

Outcome Measures

Primary Outcome Measures

Procedure-related complication [30 days]
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) [30 days]
The mRS score, and proportion of subjects achieving mRS score of 0-2
Activated Clotting Time (ACT) [During procedure]
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 [During procedure, at 24hs, 7days]
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 [During procedure, at 24hs, 7days, 30days]
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 [During procedure, at 24hs, 7days, 30days]
Any bleeding as defined by the BARC definition (except grade 4) Any bleeding as defined by the GUSTO definition
Intracranial hemorrhage [During procedure, at 24hs, 7days, 30days]
Intracranial hemorrhage and Symptomatic intracranial hemorrhage
Heparin-induced thrombocytopenia(HIT) [7days]
defined as a platelet count decrease ofmore than50%or more than 150 × 109/L frombaseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Changhai Hospital
The First Affiliated Hospital of Zhengzhou University
Zhejiang University
Wuhan University
Qilu Hospital of Shandong University
The First People's Hospital of Changzhou

Investigators

Principal Investigator: Jianmin Liu, M.D., Neurosurgical Department of Changhai Hospital
Principal Investigator: Sheng Guan, M.D., Neurointerventional Department, The First Affiliated Hospital of Zhengzhou University