APEX-STROKE EAGLE Domain (EAGLE) (EAGLE)

Early Surgical Bundle for Intracerebral Hemorrhage (EAGLE) Domain of the APEX-STROKE Adaptive Platform Trial

In this domain of APEX-STROKE, participants with acute spontaneous supratentorial intracerebral haemorrhage (ICH) who meet the domain-specific eligibility criteria will be randomised to either an early surgical bundle or guideline-based standard care. Intervention: Early minimally invasive surgery (MIS) shall be initiated within 8 hours of symptom onset; intensive systolic blood pressure control (target range: 130-140 mmHg) shall be achieved within 1 hour post-randomization and maintained for 72 hours post-randomization; tranexamic acid (TXA) hemostatic therapy: A 1-g loading dose shall be intravenously infused over 10 minutes, followed by an 8-hour continuous intravenous infusion of a 1-g maintenance dose; the entire regimen must be initiated within 30 minutes post-randomization. Control condition: All patient management shall strictly adhere to local institutional guidelines for intracerebral hemorrhage (ICH) diagnosis and treatment; MIS is recommended to be prohibited within 12 hours of symptom onset (except for emergency life-saving surgery); blood pressure management shall be conducted in accordance with local guidelines; the use of TXA is not recommended.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke; Intracerebra Hemorrhage
• Intervention / Treatment: Other: Early surgical bundle; Other: Guideline-Based Standard Care

• Study Type: Interventional
• Enrollment (Estimated): 878
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years;
2. Confirmed diagnosis of spontaneous supratentorial intracerebral hemorrhage (ICH) via cerebral imaging;
3. Randomization completed within 6 hours of symptom onset (or last known normal state), with the ability to initiate MIS within 8 hours of ICH onset;
4. Hematoma volume ranging from 20 to 80 mL;
5. National Institutes of Health Stroke Scale (NIHSS) score ≥ 8;
6. Glasgow Coma Scale (GCS) score ≥ 8;
7. Provision of written informed consent (or signed by an authorized representative).

Exclusion Criteria:

1. Secondary causes of hemorrhage (e.g., structural abnormalities including arteriovenous malformations, cerebral aneurysms, tumors, trauma) or hemorrhagic transformation of acute ischemic stroke;
2. Isolated intraventricular hemorrhage, or brainstem/cerebellar hemorrhage;
3. Severe chronic kidney disease or liver failure;
4. High risk of mortality within 7 days, or poor adherence to study treatment or follow-up;
5. Severe comorbidities (e.g., cancer, chronic obstructive pulmonary disease, heart failure, significant pre-stroke disability [modified Rankin Scale (mRS) score 3-5]) that may confound outcome assessment;
6. Other conditions judged by the investigator to be unsuitable for MIS (e.g., brain herniation, etc.);
7. Definite indications or contraindications for antihypertensive therapy of different intensities;
8. Specific contraindications to any component of the planned antihypertensive medications (e.g., patients with allergy or hypersensitivity to any ingredient);
9. Patients with contraindications to tranexamic acid (TXA), including: those allergic or hypersensitive to TXA or its excipients, patients with active thrombotic disorders, individuals with hereditary or acquired thrombophilia, patients with subarachnoid hemorrhage, and those with upper urinary tract bleeding complicated by gross hematuria, etc.;
10. Patients known at enrollment to be receiving therapeutic anticoagulation with warfarin or low-molecular-weight heparin (users of direct oral anticoagulants are eligible for inclusion and not excluded).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Early Surgical Bundle; Participants in this arm receive an early surgical bundle consisting of minimally invasive surgery (MIS), intensive blood pressure management, and tranexamic acid (TXA) haemostatic therapy, in addition to guideline-based standard care for acute spontaneous supratentorial intracerebral haemorrhage.	Other: Early surgical bundle; Early Minimally Invasive Surgery (MIS): Minimally invasive surgery (needle aspiration/minimally invasive hematoma evacuation) shall be initiated as soon as practicable post-randomization, with a mandatory initiation window within 8 hours of symptom onset; postoperative residual hematoma volume shall be controlled to < 10 mL.; Intensive Blood Pressure Management: Antihypertensive therapy shall be initiated immediately post-randomization and must be implemented preoperatively. Systolic blood pressure (SBP) shall be titrated to the target range of 130-140 mmHg within 1 hour and maintained at this target for 72 hours post-randomization (sustained throughout the entire perioperative period).; Hemostatic Therapy: Tranexamic acid (TXA) shall be administered immediately post-randomization: a loading dose of 1 g diluted in 100 mL of fluid, infused intravenously over 10 minutes; followed by a continuous intravenous infusion of 1 g in 250 mL of fluid over 8 hours.
Active Comparator: Active Comparator: Guideline-Based Standard Care; Participants in this arm receive guideline-based standard care for acute spontaneous supratentorial intracerebral haemorrhage. Clinical assessment, investigations, monitoring, blood pressure management, surgical decisions, and supportive treatment are determined by the treating clinical team according to local institutional guidelines. TXA should be avoided. If surgery is required, it should generally be initiated ≥12 hours after ICH symptom onset unless emergency life-saving surgery is clinically necessary. Surgery is not recommended for participants with a haematoma volume of 20-30 mL.	Other: Guideline-Based Standard Care; Guideline-based standard care for acute intracerebral haemorrhage is provided according to local institutional guidelines. Treatment decisions, including monitoring, blood pressure management, neurosurgical intervention, vasoactive support, mechanical ventilation, fluid therapy, and other supportive care, are determined by the treating clinical team. TXA should be avoided. If surgery is clinically required, it should generally be initiated ≥12 hours after ICH symptom onset unless emergency life-saving surgery is necessary.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Utility-Weighted Modified Rankin Scale (UW-mRS) Score at 6 Months	Functional outcome will be assessed using the utility-weighted modified Rankin Scale (UW-mRS) by a trained central assessor blinded to treatment allocation. The UW-mRS incorporates the functional health states represented by the modified Rankin Scale into a utility-weighted measure of overall functional outcome.	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
National Institutes of Health Stroke Scale (NIHSS) Score	Neurological impairment will be assessed using the National Institutes of Health Stroke Scale (NIHSS). Higher scores indicate greater neurological impairment.	24 hours after randomization, 7 days after randomization or earlier at hospital discharge
Rebleeding	The occurrence of rebleeding will be assessed during the early post-randomization period. The outcome will be reported as the number and proportion of participants experiencing a rebleeding event.	Within 7 days after randomization or earlier at hospital discharge
Poor Functional Outcome	Poor functional outcome will be defined as a modified Rankin Scale (mRS) score of 3-6. The outcome will be reported as the number and proportion of participants with mRS scores of 3-6.	180 days
Mortality	Mortality will be assessed as the number and proportion of participants who have died from any cause during follow-up.	180 days
Disability	Disability will be defined as a modified Rankin Scale (mRS) score of 3-5 and will be reported as the number and proportion of participants meeting this criterion.	180 days
Health-Related Quality of Life Assessed by EQ-5D-5L	Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L).	180 days

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Huashan Hospital; First Affiliated Hospital of Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): February 28, 2030

Study Registration Dates

• First Submitted: August 24, 2026
• First Submitted That Met QC Criteria: August 24, 2026
• First Posted (Actual): August 27, 2026

Study Record Updates

• Last Update Posted (Actual): August 27, 2026
• Last Update Submitted That Met QC Criteria: August 24, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: APEX-STROKE_EAGLE DOMAIN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No