Tranexamic Acid with Intensive Blood Pressure Management in Ultra-Early Intracerebral Hemorrhage

Official title

Safety and Efficacy of Intravenous Tranexamic Acid with Intensive Blood Pressure Management in Ultra-Early Intracerebral Hemorrhage

Overview

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

• Drug intravenous tranexamic acid (TXA) infusion
  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.
• Drug Placebo
  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.

Primary outcome measures

• modified Rankin Scale (mRS) of 0-3 at 90 days [Time frame: 90 ± 7 days]

Secondary outcome measures (12)

• Hematoma expansion at 24 hours [Time frame: 24±3 hours]
• Absolute intracerebral haematoma growth at 24 hours [Time frame: 24±3 hours]
• Relative intracerebral haematoma growth at 24 hours [Time frame: 24±3 hours]
• Intraventricular hematoma (IVH) growth at 24 hours [Time frame: 24±3 hours]
• National Institutes of Health Stroke Scale (NIHSS) score at 24 hours [Time frame: 24±3 hours]
• Neurologic deterioration in first 24 hours [Time frame: 24±3 hours]
• Received surgical intervention within 7 days [Time frame: Within 7±3 days]
• modified Rankin Scale (mRS) score at 90 days [Time frame: 90±7 days]
• modified Rankin Scale (mRS) score of 0-4 at 90 days [Time frame: 90±7 days]
• Utility weighted modified Rankin Scale (mRS) score at 90 days [Time frame: 90±7 days]
• Major thromboembolic events [Time frame: Within 90±7 days]
• Death due to any cause within 90 days [Time frame: Within 90±7 days]

Eligibility criteria

Inclusion criteria

• Age between 18 to 80 years old;
• A definite diagnosis of supratentorial brain parenchymal hemorrhage by non-contrast cranial CT scan;
• Hemorrhage volume less than 40 mL, as calculated using the ABC/2 method, with ultra-early hemorrhage growth (uHG) 10 mL/h or higher;
• A clear time of symptom onset, and the randomization must occur within 2 hours from the onset;
• At least two measurements of systolic blood pressure that are ≥150 mmHg and <220 mmHg, with at least a 2-minute interval between measurements.;
• Baseline NIHSS of 8 or higher, or unilateral limb muscle strength of 0-3 grades;
• GCS score greater than 8;
• The patient or their legal representative has signed an informed consent form.

Exclusion criteria

• Pre-illness mRS > 2;
• Primary thalamic hemorrhage or intracerebral hemorrhage that has extended into the ventricles;
• Scheduled for surgical intervention (i.e., hematoma evacuation, craniectomy);
• Secondary ICH from tumors, AVMs, and aneurysms;
• Traumatic brain injury-related hemorrhage;
• Recent stroke, TIA, or thrombolytic therapy;
• On anticoagulants;
• Blood disorders, platelets <50,000/µL, or INR ≥1.8;
• Antihypertensive therapy contraindications;
• Indications for immediate blood pressure reduction;
• Active thrombosis or thromboembolic history;
• Hereditary or acquired thrombophilia;
• Acquired color vision deficiency;
• Epilepsy history;
• GFR <90 mL/min;
• Elevated ALT or liver disease;
• Allergy to TXA or antifibrinolytics;
• Life expectancy <12 months;
• Pregnant or lactating women;
• In other interventional clinical trials;
• Other investigator-defined ineligibilities.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 2 centers

• Xuanwu Hospital, Capital Medical University — Beijing
• Xuanwu Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT06760078 · TIME-ICH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗