Historical Reference Page
This is a historical reference page. This trial preceded the modern evidence base. It is presented as a predecessor reference. See ENRICH (2024) for the modern successor trial that established minimally invasive evacuation for selected lobar intracerebral hemorrhage.
MISTIE III Trial: Minimally Invasive Surgery Plus rt-PA for ICH Evacuation
In patients with supratentorial intracerebral hemorrhage of 30 mL or larger, does image-guided catheter placement plus intermittent alteplase improve 1-year functional outcome compared with standard medical management?
Hanley et al. (Lancet 2019) · doi:10.1016/S0140-6736(19)30195-3 · 506 patients
Population
Included
- Supratentorial spontaneous ICH 30 mL or larger on baseline CT
- Age 18 years or older
- At least 12 hours post-ictus (clinical stability required)
- Hematoma accessible for stereotactic catheter placement
- GCS 5 or greater
Age and diagnosis
- Aged 18 years or older
- Spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more
Severity markers
- Glasgow Coma Scale (GCS) score of 14 or less or National Institutes of Health Stroke Scale (NIHSS) score of 6 or higher
Baseline function
- Modified Rankin Scale (mRS) score of 0 or 1 before the bleed
Clot stability
- An intracerebral haemorrhage that remained the same size (growth less than 5 mL) for at least 6 hours after diagnostic CT
Baseline coagulation and blood pressure
- 6 hours or more after diagnostic CT, an international normalised ratio of 1.3 or less, a normal activated partial thromboplastin time, and blood pressure stability
Excluded
- Infratentorial (posterior fossa) hemorrhage
- ICH secondary to anticoagulation, AVM, aneurysm, or tumor
- Planned early craniotomy within 24 hours
- Intraventricular hemorrhage causing obstructive hydrocephalus requiring immediate intervention
- INR above 1.5 or platelets below 100,000 at enrollment
Stated in the publication
- Expressed care limitations
- Deemed to have life-threatening mass effect requiring surgery
- The full list of inclusion and exclusion criteria is in the appendix; the complete exclusion list is not reproduced in the main publication text
Source: Hanley et al., Lancet 2019· Retrieved 2026-06-09
Primary Outcome — mRS 0-3 at 1 Year
506 patients; image-guided catheter + alteplase vs standard medical management; supratentorial ICH ≥30 mL
In 506 patients with supratentorial ICH 30 mL or larger randomized to image-guided catheter plus alteplase or standard medical management, MISTIE did not significantly improve functional independence (mRS 0-3) at 1 year. mRS 0-3 was achieved in 45% (110 of 245) in the MISTIE group versus 41% (103 of 250) in the standard care group (adjusted OR 1.20, 95% CI 0.81 to 1.81, P=0.33). A pre-specified subgroup analysis showed a significant benefit in patients achieving end-of-treatment hematoma volume 15 mL or less (OR approximately 1.79, 95% CI 1.03 to 3.12), suggesting that the degree of hematoma reduction, not just the technique, is the critical determinant of outcome.
Visualization not shown for predecessor reference pages. See source paper for figures.
Trial Design
MISTIE III was an international phase 3 RCT enrolling patients with supratentorial ICH 30 mL or larger who were at least 12 hours from ictus and clinically stable. A CT-guided stereotactic catheter was placed into the hematoma and alteplase (1 mg every 8 hours, up to 9 doses over approximately 72 hours) was instilled to lyse the clot; fluid was drained passively. The target was residual hematoma 15 mL or less before catheter removal. The 1-year follow-up was longer than most surgical ICH trials. MISTIE differed fundamentally from ENRICH in technique: catheter-based lysis versus trans-sulcal surgical aspiration, with the latter achieving faster and more complete evacuation.
Safety
Procedural symptomatic intracranial hemorrhage occurred in 5.8% of MISTIE patients during the treatment period versus 1.9% in the standard care group. Bacterial meningitis or ventriculitis occurred in 5.7% of MISTIE patients from prolonged catheter indwelling. There was no significant difference in overall 1-year mortality between groups.