Endovascular Therapy for Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Summary

Cerebral vasospasm is a common and serious complication after aneurysmal subarachnoid hemorrhage and is an important cause of delayed cerebral ischemia and poor neurological outcomes. Although standardized medical management is widely used, effective treatment options for cerebral vasospasm remain limited.

Endovascular treatment, including intra-arterial drug infusion and mechanical angioplasty, may relieve vasospasm and improve cerebral perfusion after aneurysmal subarachnoid hemorrhage. However, most available evidence comes from retrospective or observational studies, and high-quality randomized evidence remains insufficient. Milrinone is a phosphodiesterase inhibitor with multiple potentially beneficial effects, including vasodilation, positive inotropic activity, anti-inflammatory properties, and endothelial protection. These effects may make milrinone a promising therapeutic agent for relieving cerebral vasospasm, reducing delayed cerebral ischemia, and ultimately improving clinical outcomes after aneurysmal subarachnoid hemorrhage.

This study is a multicenter, prospective, randomized controlled clinical trial designed to evaluate whether early continuous milrinone-based endovascular therapy improves outcomes in patients with cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Eligible participants will be randomly assigned to receive either standardized medical management alone or milrinone-based endovascular therapy plus standardized medical management. In the intervention group, patients will receive intra-arterial milrinone during endovascular treatment, with mechanical angioplasty when clinically indicated, followed by continuous intravenous milrinone infusion for 72 hours after intra-arterial administration.

The study will evaluate whether this continuous treatment strategy reduces poor neurological outcomes at 3 months after randomization. It will also assess the effects of treatment on delayed cerebral ischemia, vasospasm resolution, cognitive function, quality of life and so on. The results of this trial may provide high-quality evidence for early continuous milrinone-based endovascular therapy as a treatment strategy for cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

Conditions

• Subarachnoid Hemorrhage, Aneurysmal
• Cerebral Vasospasm After Subarachnoid Hemorrhage

Interventions

OTHER

Intra-arterial and Intravenous Milrinone Therapy

Continuous milrinone-based endovascular therapy will be administered in addition to standardized medical management. Cerebral angiography will first be performed, followed by intra-arterial infusion of milrinone 8 mg into the artery supplying the vasospastic territory over approximately 30 minutes. If vasodilation is incomplete, the infusion may be repeated once in the same territory. For diffuse vasospasm, milrinone may be administered in different vascular territories, with a maximum total intra-arterial dose of 24 mg. If severe proximal stenosis persists after intra-arterial treatment, mechanical angioplasty may be performed at the operator's discretion. After intra-arterial treatment, intravenous milrinone will be continued for 72 hours, starting at 0.5 mcg/kg/min and gradually increasing to a maximum of 1.5 mcg/kg/min when clinically needed and well tolerated. If vasospasm recurs, the treatment protocol may be repeated at the investigator's discretion.

OTHER

Standardized Medical Management

Standardized medical management will be provided after aneurysm treatment for aSAH. It will include oral or enteral nimodipine at a total daily dose of 360 mg, fluid management with 24-hour intake and output monitoring to maintain euvolemia, blood pressure augmentation when clinically indicated to support cerebral perfusion, and other guideline-recommended supportive treatments.

Sponsors & Collaborators

• The First Affiliated Hospital of Zhengzhou University

  collaborator OTHER

• Hebei General Hospital

  collaborator OTHER

• Nanfang Hospital, Southern Medical University

  collaborator OTHER

• Henan Provincial People's Hospital

  collaborator OTHER

• Binzhou Medical University

  collaborator OTHER

• Hunan University of Medicine General Hospital

  collaborator OTHER

• First Affiliated Hospital of Harbin Medical University

  collaborator OTHER

• Second Affiliated Hospital, Zhejiang University, School of Medicine

  collaborator OTHER

• First Affiliated Hospital of Wannan Medical College

  collaborator OTHER

• Zhongnan Hospital

  collaborator OTHER

• The First Affiliated Hospital of Nanchang University

  collaborator OTHER

• First Affiliated Hospital of Xinjiang Medical University

  collaborator OTHER

• Chinese PLA General Hospital

  collaborator OTHER

• Shaoyang Central Hospital

  collaborator UNKNOWN

• Ji an central people's Hospital

  collaborator UNKNOWN

• The second People's Hospital of Guiyang, China

  collaborator UNKNOWN

• Beijing Tiantan Hospital

  lead OTHER

Principal Investigators

• Xinjian Yang, MD · Beijing Tiantan Hospital

• Liping Liu, MD · Beijing Tiantan Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-03

Primary Completion

2028-12-31

Completion

2029-12-31

Countries

• China

Study Locations