Clinical trial NCT05460793: Dutch Intracerebral Hemorrhage Surgery Trial
Official title: Dutch ICH Surgery Trial; Minimally Invasive Endoscopy-guided Surgery for Spontaneous Supratentorial Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Intracerebral Hemorrhage
Minimally Invasive Surgical Procedures
Endoscopic Surgical Procedures
Keywords: Intracerebral Hemorrhage
Surgical Procedures, Minimally Invasive
Surgical Procedures, Endoscopic
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Dutch National Health Care Institute
name: Penumbra Inc.
First posted: 2022-07-15
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, randomized, open, blinded endpoint (PROBE) clinical trial
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: The full protocol is available at: http://dutch-ich.nl/

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or older;
2. NIHSS ≥ 2;
3. Supratentorial non-traumatic ICH confirmed by non-contrast CT, without a CT-angiography confirmed causative vascular lesion (e.g. aneurysm, arteriovenous malformation \[AVM\], dural arteriovenous fistula \[DAVF\], cerebral venous sinus thrombosis \[CVST\]), or other known underlying lesion (e.g. tumor, cavernoma);
4. Minimal hematoma volume of 10 mL;
5. Intervention can be started within 8 hours of symptom onset;
6. Written informed consent (deferred).

Exclusion Criteria:

1. Considerable pre-stroke dependency in activities of daily living, defined as a pre-stroke mRS ≥3;
2. ICH-GS score ≥11;
3. Hemorrhage due to hemorrhagic transformation of an infarct;
4. Untreated coagulation abnormalities, including INR \&gt;1.3 (point of care measurement allowed), treatment with heparin and treatment with factor Xa inhibitors. Patients on vitamin K antagonist can be included after correction of the INR, and patients on dabigatran (direct thrombin inhibitor) can be included after reversal of dabigatran with idarucizumab;
5. Moribund (e.g. coning, bilateral dilated unresponsive pupils), or progressively deteriorating clinical course with imminent death;
6. Pregnancy (note: most patients will be beyond childbearing age);
7. DIST-INFLAME sub-study: patients that use immunosuppressive or immune-modulating medication.

Primary outcomes:
measure: modified Rankin Scale (mRS) at 180 days
timeFrame: 180 days (±14 days)
Secondary outcomes:
measure: mRS at 90 days
timeFrame: 90 days (±14 days)
measure: mRS at 365 days
timeFrame: 365 days (±14 days)
measure: Favorable outcome, defined as a mRS of 0-2 at 90 days
timeFrame: 90 days (±14 days)
measure: Favorable outcome, defined as a mRS of 0-2 at 180 days
timeFrame: 180 days (±14 days)
measure: Favorable outcome, defined as a mRS of 0-2 at 365 days
timeFrame: 365 days (±14 days)
measure: Favorable outcome, defined as a mRS of 0-3 at 90 days
timeFrame: 90 days (±14 days)
measure: Favorable outcome, defined as a mRS of 0-3 at 180 days
timeFrame: 180 days (±14 days)
measure: Favorable outcome, defined as a mRS of 0-3 at 365 days
timeFrame: 365 days (±14 days)
measure: All other possible dichotomizations of the mRS at 90 days
timeFrame: 90 days (±14 days)
measure: All other possible dichotomizations of the mRS at 180 days
timeFrame: 180 days (±14 days)
measure: All other possible dichotomizations of the mRS at 365 days
timeFrame: 365 days (±14 days)
measure: National Institute of Health Stroke Scale (NIHSS) at 6 days (±1 day)
timeFrame: 6 days (±1 day)
measure: Death at 90 days
timeFrame: 90 days (±14 days)
measure: Death at 180 days
timeFrame: 180 days (±14 days)
measure: Death at 365 days
timeFrame: 365 days (±14 days)
measure: Barthel Index at 90 days
timeFrame: 90 days (±14 days)
measure: Barthel Index at 180 days
timeFrame: 180 days (±14 days)
measure: Barthel Index at 365 days
timeFrame: 365 days (±14 days)
measure: EuroQol 5D-5L at 90 days
timeFrame: 90 days (±14 days)
measure: EuroQol 5D-5L at 365 days
timeFrame: 180 days (±14 days)
measure: EuroQol 5D-5L at 365 days
timeFrame: 365 days (±14 days)
measure: Stroke-Specific Quality of Life scale at 90 days
timeFrame: 90 days (±14 days)
measure: Stroke-Specific Quality of Life scale at 180 days
timeFrame: 180 days (±14 days)
measure: Stroke-Specific Quality of Life scale at 365 days
timeFrame: 365 days (±14 days)
measure: iMTA Medical Consumption Questionnaire (iMCQ) at 90 days
timeFrame: 90 days (±14 days)
measure: iMTA Medical Consumption Questionnaire (iMCQ) at 180 days
timeFrame: 180 days (±14 days)
measure: iMTA Medical Consumption Questionnaire (iMCQ) at 365 days
timeFrame: 365 days (±14 days)
measure: iMTA Productivity Cost Questionnaire (iPCQ) at 90 days
timeFrame: 90 days (±14 days)
measure: iMTA Productivity Cost Questionnaire (iPCQ) at 180 days
timeFrame: 180 days (6 months)
measure: iMTA Productivity Cost Questionnaire (iPCQ) at 365 days
timeFrame: 365 days (±14 days)
measure: iMTA Valuation of Informal Care Questionnaire (iVICQ) at 90 days
timeFrame: 90 days (±14 days)
measure: iMTA Valuation of Informal Care Questionnaire (iVICQ) at 180 days
timeFrame: 180 days (±14 days)
measure: iMTA Valuation of Informal Care Questionnaire (iVICQ) at 365 days
timeFrame: 365 days (±14 days)
measure: Home time at 90 days
timeFrame: 90 days (±14 days)
measure: Home time at 180 days
timeFrame: 180 days (±14 days)
measure: Home time at 365 days
timeFrame: 365 days (±14 days)
measure: Patient location at 90 days
timeFrame: 90 days (±14 days)
measure: Patient location at 180 days
timeFrame: 180 days (±14 days)
measure: Patient location at 365 days
timeFrame: 365 days (±14 days)
measure: Death within 24 hours
timeFrame: 24 hours
measure: Procedure related complications within 7 days
timeFrame: 7 days
measure: Case-fatality at 7 days
timeFrame: 7 days
measure: Case-fatality at 30 days
timeFrame: 30 days
measure: Percentage volume reduction based at 24 hours
timeFrame: 24 hours
measure: Percentage of participants with hematoma volume reduction ≥70%
timeFrame: 24 hours
measure: Percentage of participants with hematoma volume reduction ≥80%
timeFrame: 24 hours
measure: Percentage of participants with remaining hematoma volume ≤10mL
timeFrame: 24 hours
measure: Percentage of participants with remaining hematoma volume ≤15mL
timeFrame: 24 hours
measure: Conversion to craniotomy
timeFrame: 24 hours
Other outcomes:
measure: Perihematomal edema at 6 days (±1 day)
timeFrame: 6 days (±1 day)
measure: Immune and metabolomic profiles in venous blood at 3 days
timeFrame: 3 days
measure: Immune and metabolomic profiles in venous blood at 6 days (±1 day)
timeFrame: 6 days (±1 day)
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
city: The Hague
country: Netherlands
facility: Haaglanden Medical Center
city: Tilburg
country: Netherlands
facility: Elisabeth-TweeSteden Hospital
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Zwolle
country: Netherlands
facility: Isala
Study officials:
affiliation: Radboud University Medical Center
name: Catharina JM Klijn, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Erasmus Medical Center
name: Ruben Dammers, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: