Background: Intracerebral hemorrhage (ICH) accounts for 16-19% 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 possibly early blood pressure lowering, there is currently no treatment of proven benefit. Surgical treatment has so far not been proven effective. In the largest trials STICH I and II, and MISTIE III, the median time to treatment was more than 24 hours, which may be an important explanation for the lack of a treatment effect. A recent meta-analysis of randomized controlled trials showed that surgical treatment may be beneficial, in particular with minimally invasive procedures and when performed early. In the Dutch ICH Surgery pilot study, we showed that early minimally invasive endoscopy-guided surgical treatment performed within 8 hours of symptom onset in patients with supratentorial ICH is safe and technically effective. We hypothesize that early minimally invasive endoscopy-guided surgery improves the outcome in patients with supratentorial spontaneous ICH. Objectives: 1. To study whether minimally invasive endoscopy-guided surgery, in addition to standard medical management, for the treatment of spontaneous supratentorial ICH performed within 8 hours of symptom onset, improves functional outcome in comparison with standard medical management alone; 2. Determine whether patients treated with minimally invasive surgery develop less perihematomal edema on non-contrast CT at day 6 (±1 day) than controls, and whether the CT perfusion permeability surface-area product around the ICH at baseline modifies this effect (DIST-INFLAME); 3. Compare immune profiles over time in peripheral venous blood between surgically treated patients and controls (DIST-INFLAME); 4. To assess the cost-effectiveness and budget-impact of minimally invasive endoscopy-guided surgery for the treatment of spontaneous supratentorial ICH performed within 8 hours of symptom onset. Study design: A multicenter, prospective, randomized, open, blinded endpoint clinical trial. Study population: We aim to include 600 patients of ≥ 18 years with a spontaneous supratentorial ICH with a hematoma volume of ≥ 10 mL and a NIHSS of ≥ 2. Patients with an aneurysm, arteriovenous malformation (AVM), dural arteriovenous fistula (DAVF), or cerebral venous sinus thrombosis (CVST) as cause of their ICH will be excluded based on the admission CT-angiography. Patients with a known tumor or cavernoma will also be excluded. For DIST-INFLAME (the second and third objective), we will include 200 patients; 100 randomized to intervention and 100 randomized to standard medical management. Intervention: Patients will be randomized (1:1) to minimally invasive endoscopy-guided surgery performed within 8 hours of symptom onset in addition to standard medical management or to standard medical management alone. Primary study outcome: the modified Rankin scale (mRS) score at 180 days. The treatment effect will be estimated with ordinal logistic regression analysis as common odds ratio, adjusted for prespecified prognostic factors. Secondary outcomes: mRS score at 90 and 365 days; favorable outcome (defined as a mRS 0-2 and 0-3) and all other possible dichotomizations of the mRS at 90, 180 and 365 days; NIHSS at day 6 (±1 day); death, Barthel Index, EuroQol-5D-5L, SS-QOL, iMCQ, iPCQ and iVICQ at 90, 180 and 365 days. Safety outcomes will be death within 24 hours, at 7 and at 30 days and procedure-related complications within 7 days. Technical effectiveness outcomes will be percentage volume reduction based on the baseline CT and CT at 24 hours (± 6 hours), percentage of participants with clot volume reduction ≥70%, and ≥80%, and with remaining clot volume ≤10mL, and ≤15mL, and conversion to craniotomy. In DIST-INFLAME, outcomes will include perihematomal edema at 6 days (±1 day), functional outcome at 180 days and immune and metabolomic profiles at 3 (± 12 hours) and 6 days (±1 day).
The full protocol is available at: http://dutch-ich.nl/
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
600
The devices allowed into the trial, are minimally invasive neuronavigation integrated endoscopy-guided devices that are CE approved and admissible by the steering committee. Currently, only the Artemis Neuro Evacuation Device (Penumbra Inc, Alameda, California, USA) is available and CE approved.
Amsterdam University Medical Center
Amsterdam, Netherlands
RECRUITINGMedisch Spectrum Twente
Enschede, Netherlands
NOT_YET_RECRUITINGUniversity Medical Center Groningen
Groningen, Netherlands
NOT_YET_RECRUITINGLeiden University Medical Center
Leiden, Netherlands
NOT_YET_RECRUITINGMaastricht University Medical Center
Maastricht, Netherlands
RECRUITINGRadboud University Medical Center
Nijmegen, Netherlands
RECRUITINGErasmus University Medical Center
Rotterdam, Netherlands
RECRUITINGHaaglanden Medical Center
The Hague, Netherlands
RECRUITINGElisabeth-TweeSteden Hospital
Tilburg, Netherlands
RECRUITINGUniversity Medical Center Utrecht
Utrecht, Netherlands
RECRUITING...and 1 more locations
modified Rankin Scale (mRS) at 180 days
Ordinal shift in functional outcome assessed with the mRS at 180 days, adjusted for prespecified prognostic factors. 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.
Time frame: 180 days (±14 days)
mRS at 90 days
Time frame: 90 days (±14 days)
mRS at 365 days
Time frame: 365 days (±14 days)
Favorable outcome, defined as a mRS of 0-2 at 90 days
Time frame: 90 days (±14 days)
Favorable outcome, defined as a mRS of 0-2 at 180 days
Time frame: 180 days (±14 days)
Favorable outcome, defined as a mRS of 0-2 at 365 days
Time frame: 365 days (±14 days)
Favorable outcome, defined as a mRS of 0-3 at 90 days
Time frame: 90 days (±14 days)
Favorable outcome, defined as a mRS of 0-3 at 180 days
Time frame: 180 days (±14 days)
Favorable outcome, defined as a mRS of 0-3 at 365 days
Time frame: 365 days (±14 days)
All other possible dichotomizations of the mRS at 90 days
Time frame: 90 days (±14 days)
All other possible dichotomizations of the mRS at 180 days
Time frame: 180 days (±14 days)
All other possible dichotomizations of the mRS at 365 days
Time frame: 365 days (±14 days)
National Institute of Health Stroke Scale (NIHSS) at 6 days (±1 day)
Time frame: 6 days (±1 day)
Death at 90 days
Time frame: 90 days (±14 days)
Death at 180 days
Time frame: 180 days (±14 days)
Death at 365 days
Time frame: 365 days (±14 days)
Barthel Index at 90 days
Time frame: 90 days (±14 days)
Barthel Index at 180 days
Time frame: 180 days (±14 days)
Barthel Index at 365 days
Time frame: 365 days (±14 days)
EuroQol 5D-5L at 90 days
Time frame: 90 days (±14 days)
EuroQol 5D-5L at 365 days
Time frame: 180 days (±14 days)
EuroQol 5D-5L at 365 days
Time frame: 365 days (±14 days)
Stroke-Specific Quality of Life scale at 90 days
Time frame: 90 days (±14 days)
Stroke-Specific Quality of Life scale at 180 days
Time frame: 180 days (±14 days)
Stroke-Specific Quality of Life scale at 365 days
Time frame: 365 days (±14 days)
iMTA Medical Consumption Questionnaire (iMCQ) at 90 days
Time frame: 90 days (±14 days)
iMTA Medical Consumption Questionnaire (iMCQ) at 180 days
Time frame: 180 days (±14 days)
iMTA Medical Consumption Questionnaire (iMCQ) at 365 days
Time frame: 365 days (±14 days)
iMTA Productivity Cost Questionnaire (iPCQ) at 90 days
Time frame: 90 days (±14 days)
iMTA Productivity Cost Questionnaire (iPCQ) at 180 days
Time frame: 180 days (6 months)
iMTA Productivity Cost Questionnaire (iPCQ) at 365 days
Time frame: 365 days (±14 days)
iMTA Valuation of Informal Care Questionnaire (iVICQ) at 90 days
Time frame: 90 days (±14 days)
iMTA Valuation of Informal Care Questionnaire (iVICQ) at 180 days
Time frame: 180 days (±14 days)
iMTA Valuation of Informal Care Questionnaire (iVICQ) at 365 days
Time frame: 365 days (±14 days)
Home time at 90 days
Time frame: 90 days (±14 days)
Home time at 180 days
Time frame: 180 days (±14 days)
Home time at 365 days
Time frame: 365 days (±14 days)
Patient location at 90 days
Time frame: 90 days (±14 days)
Patient location at 180 days
Time frame: 180 days (±14 days)
Patient location at 365 days
Time frame: 365 days (±14 days)
Death within 24 hours
Time frame: 24 hours
Procedure related complications within 7 days
Time frame: 7 days
Case-fatality at 7 days
Time frame: 7 days
Case-fatality at 30 days
Time frame: 30 days
Percentage volume reduction based at 24 hours
The percentage of volume reduction based on baseline CT and CT at 24 hours (in the intervention group)
Time frame: 24 hours
Percentage of participants with hematoma volume reduction ≥70%
The percentage of participants in which the hematoma volume is reduced with 70% or more, based on the baseline CT and CT at 24 hours (in the intervention group)
Time frame: 24 hours
Percentage of participants with hematoma volume reduction ≥80%
The percentage of participants in which the hematoma volume is reduced with 80% or more, based on the baseline CT and CT at 24 hours (in the intervention group)
Time frame: 24 hours
Percentage of participants with remaining hematoma volume ≤10mL
The percentage of participants in which the hematoma volume is reduced to 10 mL or less, based on the baseline CT and CT at 24 hours (in the intervention group)
Time frame: 24 hours
Percentage of participants with remaining hematoma volume ≤15mL
The percentage of participants in which the hematoma volume is reduced to 15 mL or less, based on the baseline CT and CT at 24 hours (in the intervention group)
Time frame: 24 hours
Conversion to craniotomy
The percentage of participants in which a conversion to craniotomy was required and done (in the intervention group)
Time frame: 24 hours
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