Clinical trial NCT04532333: Efficacy and Safety of Bivalirudin Versus Heparin During Coil Embolization in Patients With Ruptured Intracranial Aneurysms
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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Subarachnoid Hemorrhage, Aneurysmal
Keywords: Anticoagulant Agents
Aneurysm, Intracranial Berry
Therapeutic Embolization
Anticoagulation Agents
Heparin Sodium
Bivalirudin
Lead sponsor: Changhai Hospital
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Zhengzhou University
name: Zhejiang University
name: Wuhan University
name: Qilu Hospital of Shandong University
name: The First People's Hospital of Changzhou
First posted: 2020-08-31
Enrollment: 236
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Procedure-related complication
timeFrame: 30 days
Secondary outcomes:
measure: Modified Rankin Scale (mRS)
timeFrame: 30 days
measure: Activated Clotting Time (ACT)
timeFrame: During procedure
measure: Procedure-related complication
timeFrame: During procedure, at 24hs, 7days
measure: Thromboembolic events
timeFrame: During procedure, at 24hs, 7days, 30days
measure: Bleeding events
timeFrame: During procedure, at 24hs, 7days, 30days
measure: Intracranial hemorrhage
timeFrame: During procedure, at 24hs, 7days, 30days
measure: Heparin-induced thrombocytopenia(HIT)
timeFrame: 7days
Other outcomes:
Locations:
Study officials:
affiliation: Neurosurgical Department of Changhai Hospital
name: Jianmin Liu, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurointerventional Department, The First Affiliated Hospital of Zhengzhou University
name: Sheng Guan, M.D.
role: PRINCIPAL_INVESTIGATOR
References: