Endovascular Therapy for Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

NCT07643922 | Not Yet Recruiting DMC

• 1 other identifier: KY2026-149-02
• Study Type: interventional
• Target: 306
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

aneurysmal subarachnoid hemorrhage; Cerebral vasospasm; Milrinone; Endovascular Therapy; Outcomes

Outcome Measures

Primary Outcomes (1)

• Neurological function prognosis

  The primary outcome is poor neurological outcome within 90 days after randomization, defined as a modified Rankin Scale (mRS) score of 3-6.

  Up to 90 days after randomization

Secondary Outcomes (8)

• Delayed cerebral ischemia

  Up to 21 days after randomization

• Vasospasm resolution rate

  Up to 14 days after randomization/at discharge

• Severity of patients' clinical condition

  Up to 21 days after randomization。

• Cognitive function assessed using the Montreal Cognitive Assessment (MoCA) at baseline and 90 Days

  at baseline and 90 days after randomization

• Health-related quality of life assessed using the EuroQol 5-Dimension questionnaire (EQ-5D) at 90 Days

  90 days after randomization

Study Arms (2)

Control Group (Standardized Medical Management Group)

ACTIVE COMPARATOR

Participants assigned to the control group will receive standardized medical management after aneurysm treatment for aSAH, including oral or enteral nimodipine at a total daily dose of 360 mg, maintenance of euvolemia, blood pressure augmentation when clinically indicated to support cerebral perfusion, and other guideline-recommended supportive treatments.

Other: Standardized Medical Management

Experimental Group (Continuous Milrinone-Based Endovascular Therapy Plus Standardized Medical Mana )

EXPERIMENTAL

Participants assigned to this arm will receive standardized medical management as described for the comparator arm plus continuous milrinone-based endovascular therapy. Endovascular angiography will be performed, followed by intra-arterial milrinone 8 mg infused into the artery supplying the vasospastic territory over approximately 30 minutes. The dose may be repeated if clinically needed, with a maximum total intra-arterial dose of 24 mg. Mechanical angioplasty may be considered for persistent severe proximal stenosis. After intra-arterial treatment, intravenous milrinone will be continued for 72 hours at 0.5 to 1.5 μg/kg/min according to clinical need and tolerability. If vasospasm recurs, the treatment protocol may be repeated at the investigator's discretion.

Other: Intra-arterial and Intravenous Milrinone Therapy; Other: Standardized Medical Management

Interventions

Standardized Medical Management OTHER

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.

Control Group (Standardized Medical Management Group); Experimental Group (Continuous Milrinone-Based Endovascular Therapy Plus Standardized Medical Mana )

Intra-arterial and Intravenous Milrinone Therapy OTHER

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.

Experimental Group (Continuous Milrinone-Based Endovascular Therapy Plus Standardized Medical Mana )

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria:
• Aged 18 to 80 years.
• SAH confirmed by cranial CT, with an intracranial aneurysm identified by CTA, MRA, or DSA and determined to be the source of bleeding.
• Prior treatment of the aneurysm by endovascular intervention or surgical clipping.
• Evidence suggestive of CVS within 14 days after onset, defined by at least one of the following:
• Clinical deterioration, including a decrease in GCS score of \>2 points and/or a new focal neurological deficit not attributable to another known neurological cause;
• TCD confirmed vasospasm, defined as mean flow velocity (MFV) \>120 cm/s in the middle cerebral artery (MCA) and Lindegaard ratio \>3, after excluding other causes of increased flow velocity such as anemia or fever;
• Vasospasm confirmed by DSA or CTA.

You may not qualify if:

• Hunt-Hess grade 5 with critical illness and inability to tolerate intervention.
• Contraindications to milrinone, including milrinone allergy, aortic or pulmonary valve stenosis, obstructive hypertrophic cardiomyopathy, acute coronary syndrome, or malignant arrhythmia.
• Perioperative procedure-related complications that may interfere with study assessment, such as significant stenosis of the parent artery.
• Irreversible cerebral infarction involving the entire vascular territory affected by vasospasm.
• Poor blood pressure control, defined as systolic blood pressure \<100 mmHg.
• Non-aneurysmal SAH, including hemorrhage due to arteriovenous malformation, vasculitis, tumor bleeding, trauma, or other non-spontaneous causes, or cases without an identified bleeding source.
• Other severe neurological disorders with substantial pre-existing disability (mRS \>3), such as progressive cognitive impairment or status epilepticus.
• Severe systemic disease, including significant cardiac, hepatic, renal, or psychiatric disorders.
• Pregnant or breastfeeding women, or women planning pregnancy during the study period.
• Any other condition considered by the investigators to make the patient unsuitable for participation or likely to limit compliance with study procedures.
• Current participation in another interventional clinical study, inability to complete follow-up assessments, or failure to provide informed consent.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• The First Affiliated Hospital of Henan Medical University: collaborator
• Ji'an Central People's Hospital: collaborator
• Hebei General Hospital: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• Henan Provincial People's Hospital: collaborator
• Binzhou Medical University: collaborator
• Hunan University of Medicine General Hospital: collaborator
• First Affiliated Hospital of Harbin Medical University: collaborator
• First Affiliated Hospital of Wannan Medical College: collaborator
• Zhongnan Hospital: collaborator
• The First Affiliated Hospital of Nanchang University: collaborator
• First Affiliated Hospital of Xinjiang Medical University: collaborator
• Chinese PLA General Hospital: collaborator
• Shaoyang Central Hospital: collaborator
• The second People's Hospital of Guiyang: collaborator
• Second Affiliated Hospital, School of Medicine, Zhejiang University: collaborator

Study Sites (1)

Department of Neurosurgery, Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100070, China

Location

Related Publications (4)

• Lakhal K, Hivert A, Alexandre PL, Fresco M, Robert-Edan V, Rodie-Talbere PA, Ambrosi X, Bourcier R, Rozec B, Cadiet J. Intravenous Milrinone for Cerebral Vasospasm in Subarachnoid Hemorrhage: The MILRISPASM Controlled Before-After Study. Neurocrit Care. 2021 Dec;35(3):669-679. doi: 10.1007/s12028-021-01331-z. Epub 2021 Sep 3.

  PMID: 34478028 RESULT

• Boulouis G, Labeyrie MA, Raymond J, Rodriguez-Regent C, Lukaszewicz AC, Bresson D, Ben Hassen W, Trystram D, Meder JF, Oppenheim C, Naggara O. Treatment of cerebral vasospasm following aneurysmal subarachnoid haemorrhage: a systematic review and meta-analysis. Eur Radiol. 2017 Aug;27(8):3333-3342. doi: 10.1007/s00330-016-4702-y. Epub 2016 Dec 21.

  PMID: 28004163 RESULT

• Fraticelli AT, Cholley BP, Losser MR, Saint Maurice JP, Payen D. Milrinone for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2008 Mar;39(3):893-8. doi: 10.1161/STROKEAHA.107.492447. Epub 2008 Jan 31.

  PMID: 18239182 RESULT

• Jabbarli R, Pierscianek D, Rolz R, Darkwah Oppong M, Kaier K, Shah M, Taschner C, Monninghoff C, Urbach H, Beck J, Sure U, Forsting M. Endovascular treatment of cerebral vasospasm after subarachnoid hemorrhage: More is more. Neurology. 2019 Jul 30;93(5):e458-e466. doi: 10.1212/WNL.0000000000007862. Epub 2019 Jul 5.

  PMID: 31278116 RESULT

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial

Interventions

Infusions, Intra-Arterial

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Infusions, Parenteral; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Xinjian Yang, MD

  Beijing Tiantan Hospital

  STUDY CHAIR

• Liping Liu, MD

  Beijing Tiantan Hospital

  STUDY CHAIR

Central Study Contacts

Wenqiang Li, MD

CONTACT

13521199810; lwqsurgeon@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: To reduce potential assessment bias, an independent Clinical Events Committee (CEC), blinded to treatment assignment, will centrally review and adjudicate all study outcomes according to predefined criteria. These outcomes will include functional assessments, such as mRS scores, cognitive function, and quality of life; imaging-based outcomes, including vasospasm relief; and suspected clinical endpoint events, including delayed cerebral ischemia and so on. Disagreements among committee members will be resolved by consensus.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director, Department of Neurosurgery

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: June 12, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)