Hypertension, Spontaneous Intracranial Hemorrhage
Conditions
Keywords
Intracranial Hemorrhage, Tranexamic acid, Intensive blood pressure lowering, Haemostatic therapy
Brief summary
This is a prospective, multicenter, randomized, quadruple-blind, placebo-controlled study. This study aims to estimate the safety and efficacy of intravenous tranexamic acid (TXA) combined with intensive blood pressure lowering in ultra-early spontaneous intracerebral hemorrhage (ICH).
Detailed description
This trial is designed to evaluate whether tranexamic acid can reduce hematoma expansion and improve functional outcomes when combined with intensive blood pressure lowering in cases of ultra-early intracerebral hemorrhage with a high risk of hematoma expansion. Participants who meet the eligibility criteria will be randomly assigned in a 1:1 ratio to either the TXA therapy group or the placebo control group. The initial infusion of 1 g of TXA or a matching placebo, along with intensive blood pressure lowering treatment, should commence as quickly as possible, ideally within 30 minutes of randomization. Following this, an additional 1 gram of TXA or a corresponding placebo will be administered via continuous intravenous infusion over 8 hours. Both groups will receive intensive blood pressure management during the first 24 hours after the onset of symptoms. Participants will be followed for 90 days after randomization for efficacy and safety outcomes.
Interventions
Intravenous tranexamic acid will be administered as an initial dose of 1 g (10mL: 1g, diluted in 90 mL normal saline) over 10 minutes, followed by a maintenance dose of 1 g over 8 hours (10mL: 1g, diluted in 240 mL normal saline). Intensive blood pressure lowering will be maintained throughout the treatment period until 24 hours after onset.
DRUGPlacebo
An intravenous placebo (10mL NS, diluted in 90mL NS) matching the specification and appearance of TXA will be administered as an initial bolus over 10 minutes, followed by a continuous infusion of placebo (10mL NS, diluted in 240mL NS) over 8 hours, with intensive blood pressure lowering maintained throughout the treatment period and continued until 24 hours after symptoms onset.
Sponsors
Beijing Municipal Health Commission
Capital Medical University
Suzhou First People's Hospital
Linyi People's Hospital
Peking University Care Luzhong Hospital
Wuzhou Red Cross Hospital
Yantai Penglai Traditional Chinese Medicine Hospital
The First Affiliated Hospital of Hebei North University
Jiaozuo Tumor Hospital
Hunan Provincial People's Hospital
The People's Hospital of Liaoning Province
The First People's Hospital of Qujing, Yunnan Province
Huizhou Third People's Hospital, Guangzhou Medical University
Nanyang Nanshi Hospital, Henan University
Xing'anmeng People's Hospital
Beijing Aerospace Center Hospital
Xuanwu Hospital, Beijing
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 18 to 80 years old; 2. A definite diagnosis of supratentorial brain parenchymal hemorrhage by non-contrast cranial CT scan; 3. Hemorrhage volume less than 40 mL, as calculated using the ABC/2 method, with ultra-early hemorrhage growth (uHG) 10 mL/h or higher; 4. A clear time of symptom onset, and the randomization must occur within 2 hours from the onset; 5. At least two measurements of systolic blood pressure that are ≥150 mmHg and \<220 mmHg, with at least a 2-minute interval between measurements.; 6. Baseline NIHSS of 8 or higher, or unilateral limb muscle strength of 0-3 grades; 7. GCS score greater than 8; 8. The patient or their legal representative has signed an informed consent form.
Exclusion criteria
1. Pre-illness mRS \> 2; 2. Primary thalamic hemorrhage or intracerebral hemorrhage that has extended into the ventricles; 3. Scheduled for surgical intervention (i.e., hematoma evacuation, craniectomy); 4. Secondary ICH from tumors, AVMs, and aneurysms; 5. Traumatic brain injury-related hemorrhage; 6. Recent stroke, TIA, or thrombolytic therapy; 7. On anticoagulants; 8. Blood disorders, platelets \<50,000/µL, or INR ≥1.8; 9. Antihypertensive therapy contraindications; 10. Indications for immediate blood pressure reduction; 11. Active thrombosis or thromboembolic history; 12. Hereditary or acquired thrombophilia; 13. Acquired color vision deficiency; 14. Epilepsy history; 15. GFR \<90 mL/min; 16. Elevated ALT or liver disease; 17. Allergy to TXA or antifibrinolytics; 18. Life expectancy \<12 months; 19. Pregnant or lactating women; 20. In other interventional clinical trials; 21. Other investigator-defined ineligibilities.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| modified Rankin Scale (mRS) of 0-3 at 90 days | 90 ± 7 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute intracerebral haematoma growth at 24 hours | 24±3 hours | — |
| Relative intracerebral haematoma growth at 24 hours | 24±3 hours | — |
| Intraventricular hematoma (IVH) growth at 24 hours | 24±3 hours | — |
| National Institutes of Health Stroke Scale (NIHSS) score at 24 hours | 24±3 hours | — |
| Neurologic deterioration in first 24 hours | 24±3 hours | Neurologic deterioration is defined as an increase of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) from baseline to 24 hours, or a decline of 2 or more points on the Glasgow Coma Scale (GCS). |
| Received surgical intervention within 7 days | Within 7±3 days | Interventions include hematoma evacuation, external ventricular drainage, and craniectomy. |
| Hematoma expansion at 24 hours | 24±3 hours | The expansion is defined as a 33% or 6 mL increase from baseline hematoma volume or develop an intraventricular hemorrhage. |
| modified Rankin Scale (mRS) score of 0-4 at 90 days | 90±7 days | — |
| Utility weighted modified Rankin Scale (mRS) score at 90 days | 90±7 days | — |
| Major thromboembolic events | Within 90±7 days | This includes ischemic stroke, myocardial infarction, and pulmonary embolism. |
| Death due to any cause within 90 days | Within 90±7 days | — |
| Severe hypotension | Within 72 hours | Hypotension with clinical consequences (including acute renal failure) that required corrective therapy with intravenous fluids, vasopressors, or hemodialysis. |
| modified Rankin Scale (mRS) score at 90 days | 90±7 days | — |
Countries
China
Contacts
Primary ContactJialu Li, MD
Backup ContactXiuhai Guo, MD, PhD
Outcome results
None listed