Endovascular Therapy for Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage (RESCUE-CV)

Capital Medical University

Status: Enrolling

Conditions: Subarachnoid Hemorrhage, Aneurysmal; Cerebral Vasospasm After Subarachnoid Hemorrhage

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

Study type: Interventional

Funder types: Other

Identifiers

NCT07643922

KY2026-149-02

Details and patient eligibility

About

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.

Enrollment: 306 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants must meet all of the following criteria:

1. Aged 18 to 80 years.

2. SAH confirmed by cranial CT, with an intracranial aneurysm identified by CTA, MRA, or DSA and determined to be the source of bleeding.

3. Prior treatment of the aneurysm by endovascular intervention or surgical clipping.

4. Evidence suggestive of CVS within 14 days after onset, defined by at least one of the following:

   1. 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;
   2. 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;
   3. Vasospasm confirmed by DSA or CTA.

Exclusion criteria

1. Hunt-Hess grade 5 with critical illness and inability to tolerate intervention.
2. Contraindications to milrinone, including milrinone allergy, aortic or pulmonary valve stenosis, obstructive hypertrophic cardiomyopathy, acute coronary syndrome, or malignant arrhythmia.
3. Perioperative procedure-related complications that may interfere with study assessment, such as significant stenosis of the parent artery.
4. Irreversible cerebral infarction involving the entire vascular territory affected by vasospasm.
5. Poor blood pressure control, defined as systolic blood pressure <100 mmHg.
6. 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.
7. Other severe neurological disorders with substantial pre-existing disability (mRS >3), such as progressive cognitive impairment or status epilepticus.
8. Severe systemic disease, including significant cardiac, hepatic, renal, or psychiatric disorders.
9. Pregnant or breastfeeding women, or women planning pregnancy during the study period.
10. Any other condition considered by the investigators to make the patient unsuitable for participation or likely to limit compliance with study procedures.
11. Current participation in another interventional clinical study, inability to complete follow-up assessments, or failure to provide informed consent.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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306 participants in 2 patient groups

Control Group (Standardized Medical Management Group)

Active Comparator group

Description:

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.

Treatment:

Other: Standardized Medical Management

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

Experimental group

Description:

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.

Treatment:

Other: Standardized Medical Management

Other: Intra-arterial and Intravenous Milrinone Therapy