Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study

Study Overview
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Brief Summary
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Background: Intracerebral hemorrhage (ICH) accounts for 15-20% of all strokes in Western Europe, and contributes profoundly to mortality and disability. Thirty day case fatality is 40% and of those surviving, only few gain independence. Except for stroke unit care and early blood pressure lowering there is currently no treatment of proven benefit. Important predictors of poor outcome are increasing age, decreasing Glasgow Coma Scale score, increasing ICH volume, presence of intraventricular hemorrhage and deep or infratentorial location. In addition, secondary injury due to development of edema and inflammatory response, contribute to disability and death. Surgical treatment, mostly comprising craniotomy, has so far not been proven effective. In the largest trials STICH and STICH II, the median time to treatment was more than 24 hours, which may be an important explanation for the lack of treatment effect. The investigators hypothesize that early, minimally-invasive, endoscopy-guided surgery improves outcome in patients with spontaneous supratentorial ICH. Objective: to study safety, feasibility and technical effectiveness of minimally-invasive endoscopy guided surgery for treatment of spontaneous supratentorial ICH and to estimate the potential effect on outcome. Study design: a multicenter, prospective intervention study (phase II) with a telephonic follow up interview at 90 and 180 days.The pilot study serves as a prelude to a randomized phase III trial in which the investigators aim to assess whether this intervention improves functional outcome at 90 and 180 days. Study population: patients with spontaneous supratentorial ICH of 18 years and older. Forty patients in three participating centers (Radboudumc, Erasmus MC and AMC) will undergo minimally-invasive endoscopy-guided surgery. Three-hundred-and-sixty patients undergoing standard medical treatment in one of 7 other participating centers, will be included as a control group. Intervention: minimally-invasive endoscopy-guided surgery within 8 hours of symptom onset, in addition to standard medical management. Primary study outcomes: safety (death within 24 hours, 7-day procedure related complications, 7-day mortality, 30-day mortality) and technical effectiveness (proportional volume reduction, proportion of participants with volume reduction > 60 and >80%, and proportion with remaining clot volume <15mL). Secondary outcomes: modified Rankin Scale score at 90 and 180 days after ICH (functional outcome).

Detailed Description
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The full protocol is available at https://dutch-ich.nl/trial-protocol-and-trial-documents.html

Official Title
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The Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study; Minimally-invasive Endoscopy-guided Surgery for Spontaneous Intracerebral Hemorrhage

Conditions
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Intracerebral Hemorrhage, Surgical Procedures, Minimally Invasive

Intervention / Treatment
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* Device: Minimally-invasive endoscopy-guided surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 NIHSS ≥ 2 Supratentorial ICH confirmed by CT, without a CT-angiography confirmed causative vascular lesion (e.g. aneurysma, arteriovenous malformation [AVM], dural arteriovenous fistula [DAVF], cerebral venous sinus thrombosis [CVST]). Minimal lesion size 10 mL Intervention can be started within 8 hours from symptoms onset; or for controls presentation within 8 hours of symptom onset. Patient's or legal representative's written informed consent Exclusion Criteria: 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 CT-angiography 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 (e.g. coning, bilateral dilated unresponsive pupils) Pregnancy (note: most patients will be beyond child bearing age; if not a pregnancy test is mandatory).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: We will include 40 patients in the surgical arm (inclusion in three hospitals) and aim for 120 matched controls in the other arm (in 7 other hospitals).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgical treatment<br>Minimally-invasive endoscopy-guided surgery or hematoma aspiration, additional to standard medical treatment. | Device: Minimally-invasive endoscopy-guided surgery<br>* Surgery started within 8 hours of onset of spontaneous intracerebral hemorrhage.<br>* Other names: Minimally-invasive endoscopy-guided hematoma aspiration;|
| No Intervention: Standard medical management<br>Standard medical treatment (treatment of bloodpressure, admission to stroke unit and supportive care, surgical treatment if necessary in case of deterioration) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death within 24 hours | Death within 24 hours after baseline. | 24 hours | 
| Neurological deterioration within 24 hours | Neurological deterioration, defined as an increase of ≥4 points on the sumscore of the NIHSS or >2 National Institutes of Health Stroke Scale (NIHSS)is a sum score, composed of 11 items, each of which scores a specific ability between 0 and 4. For each item, a score of 0 typically indicates normal function in that ability, while a higher score indicates the level of impairment. The total score varies between 0 (no symptoms at all) and 42. points on one item of NIHSS, | 24 hours | 
| Proportion of volume reduction | The proportion of volume reduction, based on baseline CT and CT at 24 hours (in the intervention group). | Baseline and 24 hours (based on the comparison baseline CT and CT at 24 hours). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedure related complications | The proportion of patients with procedure related complications at 7 days, including: rebleed, intracranial hemorrhage, epileptic seizures and intracranial infection. (in the intervention group) | 7 days | 
| Mortality at 7 days | Proportion of patients that died within 7 days after baseline | 7 days | 
| Mortality at 30 days | Proportion of patients that died within 30 days after baseline | 30 days | 
| Percentage of patients with clot volume reduction ≥60% | The proportion of patients in which the clot volume could be reduced with 60% or more, based on the comparison baseline CT and CT at 24 hours. (in the intervention group) | Baseline and 24 hours CT (the difference is measured) | 
| Percentage of patients with clot volume reduction ≥ 80% | The proportion of patients in which the clot volume could be reduced with 80% or more, based on the comparison baseline CT and CT at 24 hours. (in the intervention group) | Baseline and 24 hours CT (the difference is measured) | 
| Percentage of patients with remaining clot volume of ≤ 15mL | The proportion of patients in which due to clot removal a remaining clot volume of ≤ 15mL was established at 24 hours. (in the intervention group) | 24 hours CT | 
| Proportion of conversion to craniotomy | The proportion of patients in which a conversion to craniotomy was required and done. (in the intervention group) | 24 hours | 
| Functional outcome at 3 months | Ordinal shift in functional outcome (comparing the intervention group to the controls), assessed with the modified Rankin Scale (mRS) at 3 months. This is a six point scale in which a score of 0 means no symptoms at all, a higher score means more impairment, and a score of 6 means the participant is dead. A favorable outcome is defined as mRS 0-3 and mRS 0-2. | 3 months (90 days) | 
| Functional outcome at 6 months | Ordinal shift in functional outcome (comparing the intervention group to the controls), , assessed with the modified Rankin Scale (mRS) at 6 months. This is a six point scale in which a score of 0 means no symptoms at all, a higher score means more impairment, and a score of 6 means the participant is dead. A favorable outcome is defined as mRS 0-3 and mRS 0-2. | 6 months (180 days) | 
| National Institute of Health Stroke Scale (NIHSS) at 7 days or discharge | National Institutes of Health Stroke Scale (NIHSS)is a sum score, composed of 11 items, each of which scores a specific ability between 0 and 4. For each item, a score of 0 typically indicates normal function in that ability, while a higher score indicates the level of impairment. The total score varies between 0 (no symptoms at all) and 42. | 7 days (or at discharge from the hospital if earlier) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intracerebral Hemorrhage, Surgical Procedures, Minimally Invasive, Surgical Procedures, Endoscopic