This is a multicenter, prospective, intervention study. The study will run for two years in 11 centers in the Netherlands. Patients will be followed up at three and at six months after the occurrence of the ICH, at which point functional outcome will be assessed by means of the modified Rankin Scale. This pilot study serves as a prelude to a randomized phase III.
We will include patients with spontaneous supratentorial ICH of 18 years and older. Forty patients in three participating centers (Radboudumc, Erasmus MC, AMC) will undergo minimally-invasive endoscopy-guided surgery within 8 hours of symptom onset. In 7 other hospitals, we will include 360 consecutive patients fulfilling the same inclusion criteria who will undergo standard medical treatment during the study period as a control group.
In- and exclusion criteria
|NIHSS ≥ 2|
|Supratentorial ICH confirmed by CT, without a causative vascular lesion on CT-a (e.g. aneurysm, AVM, DAVF, CVST)|
|Minimal lesion size 10 mL (ABC/2)|
|Intervention can be started within 8 hours from symptoms onset; or for controls presentation within 8 hours of symptom onset.|
|Patients or legal representative’s written informed consent|
|Pre-stroke disability, which interferes with the assessment of functional outcome at 90 days, i.e. mRS > 2|
|Causative vascular lesion (e.g. aneurysm, AVM, DAVF, CVST) on CTA or other known underlying cause (e.g. tumor, cavernoma)|
|Untreated coagulation abnormalities, including INR > 1.3 (point of care measurement allowed) and treatment with oral thrombin or factor X antagonists; patients on vitamin K antagonist can be included after correction of the INR. |
|Current known severe infection for which antibiotic treatment at time of ICH symptom onset |
|Patient moribund (eg. coning, bilateral dilated unresponsive pupils)|
|Pregnancy (most patients will be beyond child bearing age; if not a pregnancy test is mandatory).|
Minimally-invasive endoscopy-guided surgery within 8 hours of symptom onset, in addition to standard medical management. The investigational product is: A device for minimally-invasive, endoscopy-guided hematoma removal. Currently, the 2nd generation Penumbra device, the Artemis system is available and CE approved. When other devices will become available they may be used when they are CE approved and deemed admissible by the steering committee. The surgical goal in this study is to reduce the ICH volume with at least 60%, whereas we will aim for a reduction of 75-80% or a remaining ICH volume less than 15mL.
Main study parameters/endpoints
The main outcome parameters will be safety (death within 24 hours; neurological deterioration >4 points on NIHSS at 24 hours; 7-day procedure related complications; 7-day mortality, 30 day mortality) and technical effectiveness (primary: proportional volume reduction on CT at 24 hours; others: proportion of patients with clot volume reduction ≥60% and ≥80% on CT at 24 hours; proportion of patients with remaining clot volume ≤15mL; conversion to craniotomy). Secondary parameters will be the ordinal shift on the modified Rankin Scale at 90 and 180 day of patients treated with surgery in comparison with control patients, adjusted for important prognostic variables including age, NIHSS at presentation, presence of intraventricular blood, ICH location (deep versus lobar) and presence of a spot sign.
Written informed consent will be obtained from the patient or the legal representative. Patients and their representative will be provided with as much time as needed, taking into consideration that surgical treatment will have to start within eight hours of symptom onset. If a patient regains competency during the study period, the patient will be asked to sign informed consent at that time.