Intracerebra Hemorrhage, Stroke
Conditions
Brief summary
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.
Interventions
OTHEREarly surgical bundle
1. 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. 2. 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). 3. 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.
OTHERGuideline-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.
Sponsors
Fudan University
Huashan Hospital
First Affiliated Hospital of Fujian Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Utility-Weighted Modified Rankin Scale (UW-mRS) Score at 6 Months | 180 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| National Institutes of Health Stroke Scale (NIHSS) Score | 24 hours after randomization, 7 days after randomization or earlier at hospital discharge | Neurological impairment will be assessed using the National Institutes of Health Stroke Scale (NIHSS). Higher scores indicate greater neurological impairment. |
| Rebleeding | Within 7 days after randomization or earlier at hospital discharge | 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. |
| Poor Functional Outcome | 180 days | 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. |
| Mortality | 180 days | Mortality will be assessed as the number and proportion of participants who have died from any cause during follow-up. |
| Disability | 180 days | 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. |
| Health-Related Quality of Life Assessed by EQ-5D-5L | 180 days | Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). |
Outcome results
None listed