Intracerebral Hemorrhage
Conditions
Keywords
Intracerebral Hemorrhage, Intracranial Hemorrhages, ICH, brain hemorrhage, Hemorrhage, Cerebrovascular Disorders, Brain Diseases, Minimally invasive catheter evacuation, Minimally invasive surgery, Neurosurgery, Thrombolysis, Urokinase, Medical Economic, Hospital Economics
Brief summary
TIME-ICH (TrIal of early Minimally Invasive catheter Evacuation with thrombolysis in IntraCerebral Hemorrhage) is a multicenter, randomized, adaptive clinical trial comparing best medical management to early minimally invasive surgery with thrombolysis (eMIST) in the treatment of acute spontaneous supratentorial intracerebral hemorrhage.
Detailed description
Patients presenting to the emergency department with stroke due to supratentorial, spontaneous intracerebral hemorrhage ≥20mL volume will be assessed to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomized 1:1 using central computerized allocation to early minimally invasive surgery with thrombolysis versus best medical management. The trial is prospective, randomized, open-label, blinded endpoint (PROBE) design. Adaptive sample size re-estimation will be performed when 250 patients have completed 180 days follow-up. Clinical efficacy will be determined by demonstrating an improvement in functional outcome, as determined by a blinded-assessment of the 180-day utility-weighted modified Rankin Scale (mRS).
Interventions
PROCEDUREEarly Minimally Invasive Surgery with Thrombolysis (eMIST)
Subjects will undergo minimally invasive catheter evacuation in the early stage of intracranial hemorrhage. Up to 10 doses of 50000U of urokinase will be administered through the catheter that was placed directly into the intracerebral hemorrhage.
Sponsors
Xuanwu Hospital, Beijing
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. Pre-randomization head CT demonstrating an acute, spontaneous, primary ICH; 3. ICH volume ≥ 20mL as calculated by the ABC/2 method; 4. The randomization can be completed within 8 hours after the onset of stroke symptoms (or the time last known to be well), and study intervention can reasonably be initiated within 4 hours after randomization. 5. Historical Modified Rankin Score 0 or 1; 6. Obtain informed consent from patient or legal representative.
Exclusion criteria
1. Infratentorial intraparenchymal hemorrhage including midbrain, pontine, or cerebellar; 2. Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease, venous sinus thrombosis, mass or tumor, hemorrhagic conversion of an ischemic infarct, tumor stroke, recurrence of a recent (\<1 year) ICH, as diagnosed with radiographic imaging; 3. Presence of spot sign in CT angiography; 4. Blood pressure control before randomization is ineffective, systolic blood pressure \> 220 mmHg; 5. Irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS ≤ 4; 6. Hemorrhage with apparent midbrain extension with third nerve palsy or dilated and non-reactive pupils. Other (supranuclear) gaze abnormalities are not exclusions; 7. Intraventricular extension of the Hemorrhage is visually estimated to involve \>50% of either of the lateral ventricles; 8. Any irreversible coagulopathy or known clotting disorder. 9. Platelet count \< 750,000, INR \> 1.4 after correction 10. Patients requiring long-term anti-coagulation that needs to be initiated \< 30 days from index ICH; 11. Use of 2 or more antithrombotic drugs prior to symptom onset; 12. Patients with a mechanical heart valve; 13. Positive urine or serum pregnancy test in female subjects without documented history of surgical sterilization or is post-menopausal; 14. Urokinase allergy; 15. Any concurrent serious illness that would interfere with the outcome assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease; 16. Inability or unwillingness of patient or legal representative to give written informed consent; 17. Known life-expectancy of less than 6 months; 18. Participation in a concurrent interventional medical investigation or clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional Improvement - uw-mRS | 180 days | Functional Improvement as determined by utility-weighted modified Rankin Scale (uw-mRS) which is assigned to seven levels: 1.0, 0.91, 0.76, 0.65, 0.33, 0.0, and 0.0 (with higher scores indicating a better outcome, according to patients' assessment) at 180-days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Improvement - uw-mRS | 7 days, 14 days (discharge), 30 days and 90 days | Functional Improvement as determined by utility-weighted modified Rankin Scale (uw-mRS) which is assigned to seven levels: 1.0, 0.91, 0.76, 0.65, 0.33, 0.0, and 0.0 (with higher scores indicating a better outcome, according to patients' assessment) at 7 days, 14 days/discharge, 30 days and 90 days. |
| Functional Improvement - good functional outcome | 7 days, 14 days (discharge), 30 days, 90 days and 180 days | Good functional outcome as determined by modified Rankin Scale (mRS) 0-3 at 7 days, 14 days/discharge, 30 days, 90 days and 180 days |
| Mortality | 180 days | Mortality at 180 days. |
| Clot Removal - Amount of Residual Blood | 36 hours, 7 days and 14 days (discharge) | Clot Removal will be assessed by the amount of residual blood at 36 hours, 7 days and 14 days/discharge. |
| Health-related quality of life - EQ-5D-5L | 14 days (discharge), 30 days, 90 days and 180 days | Health-related quality of life will be assessed by EuroQol five-dimension, five-level (EQ-5D-5L) which consists of two parts, a short descriptive system questionnaire and a visual analogue scale (EQ VAS) at 7 days, 14 days/discharge, 30 days, 90 days and 180 days. |
| Activities of Daily Living - Barthel Index | 14 days (discharge), 30 days, 90 days and 180 days | Activities of Daily Living will be assessed by Barthel Index at 14 days/discharge, 30 days, 90 days and 180 days. |
Countries
China
Contacts
CONTACTTao Hong, MD, PhD
CONTACTShaohua Mo, MD
Outcome results
None listed