Intracerebral Haemorrhage, Stroke
Conditions
Keywords
Intracerebral Hemorrhage, ICH, Stroke, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases, Tranexamic Acid, Antifibrinolytic Agents, Fibrin Modulating Agents, Pharmacologic Actions, Cardiovascular Agents, Therapeutic Uses, Hematologic Agents, Hemostatics, Contrast Media, Angiography, Cerebral Angiography, Tomography, X-Ray Computed
Brief summary
The aim of the study is to test if intracerebral haemorrhage (ICH) patients who have contrast extravasation on computed tomography angiography, the spot sign, have lower rates of haematoma growth when treated with tranexamic acid within 4.5 hours of stroke onset, compared to placebo.
Interventions
DRUGTranexamic Acid
DRUGPlacebo
Sponsors
Neuroscience Trials Australia
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Patients presenting with an acute ICH * Contrast extravasation within the haemorrhage, spot sign, evaluated from the CTA according to three criteria, all of which must be present: 1. Serpiginous or spot-like appearance within the margin of a parenchymal haematoma without connection to an outside vessel; 2. The density (in Hounsfield units) should be greater than that of the background haematoma (site investigators are not required to document the density); and 3. No hyperdensity at the corresponding location on non-contrast CT. * Age ≥18 years * Treatment can commence within 1 hour of initial CT and within 4.5 hours of symptom onset (or in patients with unknown time of symptom onset, the time patient was last known to be well) * Informed consent has been received in accordance to local ethics committee requirements
Exclusion criteria
* Glasgow coma scale (GCS) total score of \<8 * Brainstem ICH * ICH volume \>70 ml as measured by the ABC/2 method * ICH known or suspected by study investigator to be secondary to trauma, aneurysm, vascular malformation, haemorrhagic transformation of ischaemic stroke, cerebral venous thrombosis, thrombolytic therapy, tumor, or infection * Contrast already administered within 24 hours prior to initial CT or contraindication to imaging with CT contrast agents (e.g. known or suspected iodine allergy or significant renal failure) * Any history or current evidence suggestive of venous or arterial thrombotic events within the previous 12 months, including clinical, ECG, laboratory, or imaging findings. Clinically silent chance findings of old ischemia are not considered exclusion. * Hereditary or acquired haemorrhagic diathesis or coagulation factor deficiency. * Use of heparin, low-molecular weight heparin, GPIIb/IIIa antagonist, or oral anticoagulation (e.g. warfarin, factor Xa inhibitor, thrombin inhibitor) within the previous 14 days, irrespective of laboratory values * Pregnancy (women of childbearing potential must be tested) * Planned surgery for ICH within 24 hours * Concurrent or planned treatment with haemostatic agents (e.g. prothrombin complex concentrate, vitamin K, fresh frozen plasma, or platelet transfusion) * Participation in any investigational study in the last 30 days * Known terminal illness or planned withdrawal of care or comfort care measures. * Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ICH growth by 24±3 hours as defined by either 33% or 6 ml increase from baseline, adjusted for baseline ICH volume. | 24+/-3 hours |
Secondary
| Measure | Time frame |
|---|---|
| Death due to any cause by 3 months | within 90+/-7 days |
| modified Rankin Scale (mRS) score of 0-3 at 3 months | 90+/-7 days |
| Categorical shift in mRS at 3 months, subject to the validity of proportional odds assumption | 90+/-7 days |
| Major thromboembolic events (myocardial infarction, ischaemic stroke, pulmonary embolism) | Within 90+/-7 days |
| Absolute ICH growth volume by 24±3 hours, adjusted for baseline ICH volume | 24+/-3 hours |
| Absolute intraventricular haematoma (IVH) growth volume by 24±3 hours, adjusted for baseline IVH volume | 24+/-3 hours |
| modified Rankin Scale (mRS) score of 0-4 at 3 months | 90+/-7 days |
Other
| Measure | Time frame | Description |
|---|---|---|
| modified Rankin Scale (mRS) | 90+/-7 days | Exploratory analyses will be run with adjustments for baseline variables such as age, Glasgow Coma Scale (GCS), presence of IVH, and ICH location, and in the following subgroups: onset-to-treatment time (\<3 vs. \>3 hours); baseline ICH volume (\<30 vs. \>30 ml); anatomical location (deep, lobar, or cerebellar); IVH (absent vs. present); GCS (\>12 vs. 8-12) and age (\<70 vs. \>70). These analyses will be hypothesis generating, as the trial is not powered for them. |
| ICH growth | 24+/-3 hours | Exploratory analyses will be run with adjustments for baseline variables such as age, Glasgow Coma Scale (GCS), presence of IVH, and ICH location, and in the following subgroups: onset-to-treatment time (\<3 vs. \>3 hours); baseline ICH volume (\<30 vs. \>30 ml); anatomical location (deep, lobar, or cerebellar); IVH (absent vs. present); GCS (\>12 vs. 8-12) and age (\<70 vs. \>70). These analyses will be hypothesis generating, as the trial is not powered for them. |
Countries
Australia, Finland
Outcome results
None listed