Early Prophylactic Aspirin for Aneurysmal Subarachnoid Hemorrhage (aSAH-ASA)

Study on the Efficacy and Safety of Early Prophylactic Use of Aspirin in Improving Prognosis of Patients With Aneurysmal Subarachnoid Hemorrhage: A Multicenter, Prospective, Double-Blind, Randomized Controlled Trial

This study is a multicenter, prospective, double-blind, randomized controlled trial designed to evaluate whether early prophylactic use of aspirin improves functional outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Patients with aSAH who have undergone successful aneurysm securing will be randomly assigned to receive either aspirin plus standard care or a placebo plus standard care. The study drug will be started within 48 hours of undergone successful aneurysm securing and continued for not less than 10 days and not more than 14 consecutive days. The main goal is to compare the rate of favorable functional outcomes at 3 months between the two groups. Secondary goals include evaluating the incidence of delayed cerebral ischemia, cerebral infarction, mortality, and safety outcomes such as major bleeding events.

Study Overview

• Status: Not yet recruiting
• Conditions: Delayed Cerebral Ischemia; Aneurysmal Subarachnoid Hemorrhage (aSAH)
• Intervention / Treatment: Drug: Aspirin; Drug: Placebo

Detailed Description

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurological emergency associated with high rates of morbidity and mortality. Delayed cerebral ischemia (DCI) and subsequent cerebral infarction are major contributors to poor functional outcomes in survivors. Antiplatelet agents such as aspirin have been hypothesized to reduce the risk of microthrombosis and DCI, but evidence for their early prophylactic use in aSAH remains limited and controversial. This trial aims to investigate the efficacy and safety of early aspirin administration in improving long-term functional outcomes in aSAH patients. Eligible patients will be randomized into two groups: the intervention group will receive 100 mg of oral aspirin daily for not less than 10 days and not more than 14 consecutive days, while the control group will receive an identical placebo. All patients in both groups will receive standardized aSAH management according to current clinical guidelines, including nimodipine, blood pressure control, and supportive care. The primary endpoint is the functional outcome measured by the modified Rankin Scale (mRS) at 3 months. Secondary endpoints include incidence of clinical DCI at discharge, percentage of imaging DCI detected on CT/MRI at discharge, all-cause mortality at 3 months, and safety outcomes including major bleeding events.

• Study Type: Interventional
• Enrollment (Estimated): 388
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Weilong Huang, MD. PhD.; Phone Number: +8618807971121; Email: doctorhwl@163.com
• Study Contact Backup: Name: Zhenyu zhang, MD. PhD.; Phone Number: +8615297777969; Email: 623071778@qq.com

Study Locations

• China
  • Jiangxi
    • Ganzhou, Jiangxi, China, 341000
      • Ganzhou People's Hospital
      • Contact: Qiuhuang Jiang, MD, PhD; Phone Number: +8613607979100; Email: jiangqh1968@126.com
      • Contact: Xinyun Ye, MD, PhD; Phone Number: +8615979789987; Email: yexinyun1270@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 80 years.
2. Spontaneous subarachnoid hemorrhage (SAH) confirmed by non-contrast head CT.
3. Diagnosis of ruptured intracranial aneurysm confirmed, and successfully treated by either surgical clipping or endovascular coiling within 48 hours of ictus.
4. Hunt-Hess grade ≤ 4 or WFNS grade ≤ 4 (assessed within 48 hours of SAH onset).
5. Fisher grade 2-4 or modified Fisher grade 1-4.
6. No significant focal neurological deficit after aneurysm intervention, defined as NIHSS scores ≤ 1 in the following items: 5a (left arm motor), 5b (right arm motor), 6a (left leg motor), 6b (right leg motor), and 9 (language).
7. Pre-morbid modified Rankin Scale (mRS) score ≤ 1 prior to SAH onset.

Exclusion Criteria:

1. Hunt-Hess grade 5 or WFNS grade 5 (assessed within 48 hours of SAH onset).
2. Patients requiring any intracranial stent or non-embolic intrasaccular device during aneurysm embolization, with post-procedural need for antiplatelet therapy.
3. Angiogram-negative SAH.
4. Note: Prior history of ruptured intracranial aneurysm or re-rupture of previously treated aneurysm is not excluded.
5. Moderate-to-severe vasospasm demonstrated on pre-operative or intra-operative CTA/DSA in the emergency setting.
6. SAH caused by non-saccular aneurysms, including mycotic, blood-blister, fusiform, or dissecting aneurysms, or cases without basal cistern subarachnoid hemorrhage.
7. Significant pre-existing intracranial pathology at the time of enrollment, including but not limited to: traumatic brain injury, moyamoya disease, high suspicion or documented CNS vasculitis, severe fibromuscular dysplasia, arteriovenous malformation, arteriovenous fistula, significant cervical or intracranial atherosclerotic stenosis (≥70%), or malignant brain tumor.
8. Medical conditions requiring chronic use of antiplatelet agents (aspirin, clopidogrel, or ticagrelor), such as transient ischemic attack, myocardial infarction, atrial fibrillation, prosthetic heart valve, arteriovenous fistula, unstable angina, or other conditions requiring thromboprophylaxis.
9. Thrombocytopenia (platelet count <20,000/μL, excluding aggregation artifacts), active disseminated intravascular coagulation (DIC) at enrollment, or documented history of coagulopathy or bleeding diathesis.
10. History of gastrointestinal bleeding or major systemic hemorrhage within 30 days, hemoglobin <8 g/dL at admission, INR ≥1.5, or severe hepatic impairment defined as AST, ALT, alkaline phosphatase (AP), or GGT >2 times the upper limit of normal.
11. Creatinine clearance <30 mL/min.
12. Severe comorbidities that may confound study outcomes, including but not limited to: multiple sclerosis, dementia, major depression, immunosuppressed state or during intensive immunosuppressive therapy, cancer with expected survival <1 year, multi-organ failure, or any other condition potentially causing cognitive impairment.

13. Contraindications to aspirin therapy, including:

    • Hypersensitivity to aspirin, other salicylates, or any excipients in the formulation;
    • History of asthma induced by salicylates or NSAIDs;
    • Active peptic ulcer disease;
    • Bleeding diathesis;
    • Hepatic or renal failure;
    • Uncontrolled severe heart failure;
    • Concomitant use with methotrexate at doses ≥15 mg/week.
14. Pregnancy or positive HCG test.
15. Incomplete repair of the responsible aneurysm as judged by the treating physician, with high risk of early re-bleeding.
16. History of head trauma within 3 months prior to SAH onset.
17. Recent cerebral disease within 3 months prior to SAH onset, such as tumor, stroke, epilepsy, vasculitis, AVM, or hydrocephalus.
18. History of psychiatric illness or seizure disorder.
19. Breastfeeding women.
20. Expected survival <1 year prior to SAH onset.
21. Participation in another randomized clinical trial that may confound the evaluation of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin Group; Patients receive 100 mg aspirin once daily, initiated within 48 hours of undergone successful aneurysm securing and continued for not less than 10 consecutive days and not more than 14 consecutive days, plus standard care.	Drug: Aspirin; Aspirin 100 mg (1 tablet) administered orally, via nasogastric tube, or rectally within 48 hours after aneurysm embolization or surgical clipping, once daily, for a minimum of 10 consecutive days and a maximum of 14 consecutive days.
Placebo Comparator: Placebo Control Group; Patients receive identical-appearing placebo capsules once daily, initiated within 48 hours of undergone successful aneurysm securing and continued for not less than 10 consecutive days and not more than 14 consecutive days, plus standard care.	Drug: Placebo; Placebo 1 tablet (identical in appearance to aspirin 100 mg) administered orally, via nasogastric tube, or rectally within 48 hours after aneurysm embolization or surgical clipping, once daily, for a minimum of 10 consecutive days and a maximum of 14 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with mRS 0-2 at 90 days after randomization	The proportion of patients with modified Rankin Scale (mRS) scores ranging from 0 to 2 at 90 days after randomization.	90 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extended Glasgow Outcome Scale (eGOS) at 90 days	Functional prognosis assessed by Extended Glasgow Outcome Scale (eGOS) at 90 days after randomization.	90 days after randomization
Ordinal shift analysis of mRS at 90 days (mRS 5 and 6 combined)	Ordinal shift analysis of modified Rankin Scale scores at 90 days after randomization, with mRS grade 5 and 6 merged into one category.	90 days after randomization
Proportion of patients with mRS 0-3 at 90 days	Proportion of patients with modified Rankin Scale scores of 0 to 3 at 90 days after randomization.	90 days after randomization
Mini-Mental State Examination (MMSE) score at 90 days	Cognitive function assessed via Mini-Mental State Examination (MMSE) scale.	90 days after randomization
Extended Glasgow Outcome Scale (eGOS) at 1 year	Functional outcome assessed by Extended Glasgow Outcome Scale at 1 year after randomization.	1 year after randomization.
Ordinal shift analysis of mRS at 1 year (mRS 5 and 6 combined)	Ordinal shift analysis of modified Rankin Scale scores at 1 year after randomization, combining mRS 5 and mRS 6 into a single category.	1 year after randomization
Proportion of mRS 0-2 at 1 year	Proportion of patients with modified Rankin Scale scores of 0 to 2 at 1 year after randomization.	1 year after randomization.
Proportion of patients with mRS 0-3 at 1 year	Percentage of subjects achieving modified Rankin Scale scores from 0 to 3 at one year after randomization.	1 year after randomization.
Mini-Mental State Examination (MMSE) score at 1 year	Cognitive function evaluated by Mini-Mental State Examination (MMSE) scale.	1 year after randomization
Change in NIHSS score from baseline at discharge	Changes in National Institutes of Health Stroke Scale (NIHSS) scores at discharge compared with baseline levels.	30 days/discharge, which ever is earlier
Incidence of clinical delayed cerebral ischemia at discharge	Incidence rate of clinical delayed cerebral ischemia (DCI) observed at hospital discharge.	30 days/discharge, which ever is earlier
Percentage of radiological DCI on CT/MRI at discharge	Proportion of patients with radiological delayed cerebral ischemia confirmed by cranial CT or MRI at hospital discharge.	30 days/discharge, which ever is earlier
Lesion volume of radiological DCI on CT/MRI at discharge	Volume of lesions consistent with radiological delayed cerebral ischemia detected by cranial CT or MRI at hospital discharge.	30 days/discharge, which ever is earlier
Incidence of invasive interventions	Incidence of invasive interventions including DSA and angioplasty performed during hospitalization.	30 days/discharge, which ever is earlier
Rate of cerebrospinal fluid shunt surgery within 3 months	Proportion of patients receiving cerebrospinal fluid shunt surgery within 3 months after randomization.	Within 3 months after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality within 90 days after randomization	Total all-cause mortality rate at 90 days after randomization.	90 days after randomization
In-hospital discharge mortality	Mortality rate at the time of hospital discharge.	30 days/discharge, which ever is earlier
Incidence of symptomatic intracerebral hemorrhage	Defined as neurological deterioration with NIHSS score increased by ≥4 points combined with intracranial hemorrhage confirmed by imaging examination.	30 days/discharge, which ever is earlier
Incidence of any new-onset intracranial hemorrhage	Incidence of any new-onset intracranial hemorrhage	30 days/discharge, which ever is earlier

Collaborators and Investigators

• Sponsor: Ganzhou City People's Hospital
• Collaborators: The First Affiliated Hospital of Anhui Medical University; The First Affiliated Hospital of Nanchang University; Guizhou Provincial People's Hospital; Second Affiliated Hospital of Guangzhou Medical University; First Affiliated Hospital of Wannan Medical College; Meizhou People's Hospital; Jiangxi Provincial People's Hopital; Yichun People's Hospital; Fifth Affiliated Hospital of Guangzhou Medical University; Affiliated Hospital of Guangdong Medical University; Nanfang Hospital, Southern Medical University; Huang Shan People's Hospital; Ji'an Central People's Hospital; Jiu Jiang NO.1 People's Hospital
• Investigators: Principal Investigator: QiuHua Jiang, MD. PhD., Ganzhou People's Hospital, Ganzhou, Jiangxi Province, China; Principal Investigator: Zeguang Ren, MD. PhD., Houston Methodist, Houston, USA

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: June 7, 2026
• First Posted (Actual): June 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 7, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Aspirin; Randomized controlled trial; Delayed cerebral ischemia; Antiplatelet therapy; Functional outcome; Aneurysmal subarachnoid hemorrhage
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hemorrhage; Intracranial Hemorrhages; Pathological Conditions, Signs and Symptoms; Subarachnoid Hemorrhage; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Salicylates; Hydroxybenzoates; Aspirin
• Other Study ID Numbers: GZPH-PJB2025-420-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) cannot be shared due to patient privacy requirements, institutional policies, and legal and regulatory restrictions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No