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

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）

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.

Study Overview

• Status: Unknown
• Conditions: Subarachnoid Hemorrhage, Aneurysmal
• Intervention / Treatment: Drug: Bivalirudin 250 MG Injection; Drug: Heparin

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 Type: Interventional
• Enrollment (Anticipated): 236
• Phase: Phase 3

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS)	The mRS score, and proportion of subjects achieving mRS score of 0-2	30 days
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	During procedure
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	During procedure, at 24hs, 7days
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	During procedure, at 24hs, 7days, 30days
Bleeding events	Any bleeding as defined by the BARC definition (except grade 4) Any bleeding as defined by the GUSTO definition	During procedure, at 24hs, 7days, 30days
Intracranial hemorrhage	Intracranial hemorrhage and Symptomatic intracranial hemorrhage	During procedure, at 24hs, 7days, 30days
Heparin-induced thrombocytopenia(HIT)	defined as a platelet count decrease ofmore than50%or more than 150 × 109/L frombaseline	7days

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Collaborators: Wuhan University; Qilu Hospital of Shandong University; The First Affiliated Hospital of Zhengzhou University; Zhejiang 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

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2020
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): August 31, 2020

Study Record Updates

• Last Update Posted (Actual): August 31, 2020
• Last Update Submitted That Met QC Criteria: August 26, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Heparin Sodium; Bivalirudin; Therapeutic Embolization; Anticoagulant Agents; Aneurysm, Intracranial Berry; Anticoagulation Agents
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Intracranial Hemorrhages; Hemorrhage; Aneurysm; Subarachnoid Hemorrhage; Intracranial Aneurysm; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Heparin; Bivalirudin
• Other Study ID Numbers: CHEC2020-042

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No