- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05460793
Dutch Intracerebral Hemorrhage Surgery Trial (DIST)
Dutch ICH Surgery Trial; Minimally Invasive Endoscopy-guided Surgery for Spontaneous Supratentorial Intracerebral Hemorrhage
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:
- 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;
- 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);
- Compare immune profiles over time in peripheral venous blood between surgically treated patients and controls (DIST-INFLAME);
- 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).
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Floor NH Wilting, MD
- Phone Number: +31 24 36166 00
- Email: floor.wilting@radboudumc.nl
Study Contact Backup
- Name: Catharina JM Klijn, MD PhD
- Phone Number: +31 24 361 33 94
- Email: karin.klijn@radboudumc.nl
Study Locations
-
-
-
Amsterdam, Netherlands
- Recruiting
- Amsterdam University Medical Center
-
Principal Investigator:
- W Peter Vandertop, MD PhD
-
Sub-Investigator:
- Jonathan P Countinho, MD PhD
-
Enschede, Netherlands
- Not yet recruiting
- Medisch Spectrum Twente
-
Principal Investigator:
- Renate M Arntz, MD PhD
-
Sub-Investigator:
- Kuan H Kho, MD PhD
-
Groningen, Netherlands
- Not yet recruiting
- University Medical Center Groningen
-
Principal Investigator:
- Saloua A Akoudad, MD PhD
-
Sub-Investigator:
- J Marc C van Dijk, MD PhD
-
Sub-Investigator:
- Marieke JH Wermer, MD PhD
-
Leiden, Netherlands
- Not yet recruiting
- Leiden University Medical Center
-
Sub-Investigator:
- Wouter A Moojen, MD PhD
-
Principal Investigator:
- Ellis S van Etten, MD PhD
-
Maastricht, Netherlands
- Not yet recruiting
- Maastricht University Medical Center
-
Principal Investigator:
- Inger R de Ridder, MD PhD
-
Sub-Investigator:
- Roel Haeren, MD PhD
-
Nijmegen, Netherlands
- Recruiting
- Radboud University Medical Center
-
Principal Investigator:
- Catharina JM Klijn, MD PhD
-
Sub-Investigator:
- Hieronymus D Boogaarts, MD PhD
-
Sub-Investigator:
- Floris HBM Schreuder, MD PhD
-
Sub-Investigator:
- Floor NH Wilting, MD
-
Sub-Investigator:
- Axel Wolsink, MD
-
Rotterdam, Netherlands
- Recruiting
- Erasmus University Medical Center
-
Principal Investigator:
- Ruben Dammers, MD PhD
-
Sub-Investigator:
- Paula Janssen, MD
-
Sub-Investigator:
- Diederik WJ Dippel, MD PhD
-
Sub-Investigator:
- Nadia HC Colmer, MD
-
The Hague, Netherlands
- Not yet recruiting
- Haaglanden Medical Center
-
Principal Investigator:
- Wouter A Moojen, MD PhD
-
Sub-Investigator:
- Ido R van den Wijngaard, MD PhD
-
Tilburg, Netherlands
- Not yet recruiting
- Elisabeth-TweeSteden hospital
-
Principal Investigator:
- H Bart Brouwers, MD PhD
-
Sub-Investigator:
- Ben PW Jansen, MD PhD
-
Utrecht, Netherlands
- Recruiting
- University Medical Center Utrecht
-
Principal Investigator:
- Albert van der Zwan, MD PhD
-
Sub-Investigator:
- H Bart van der Worp, MD PhD
-
Zwolle, Netherlands
- Recruiting
- Isala
-
Principal Investigator:
- Wilmar MT Jolink, MD PhD
-
Sub-Investigator:
- Mahrouz Foumani, MD PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age 18 years or older;
- NIHSS ≥ 2;
- 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);
- Minimal hematoma volume of 10 mL;
- Intervention can be started within 8 hours of symptom onset;
- Written informed consent (deferred).
Exclusion Criteria:
- Considerable pre-stroke dependency in activities of daily living, defined as a pre-stroke mRS ≥3;
- ICH-GS score ≥11;
- Hemorrhage due to hemorrhagic transformation of an infarct;
- Untreated coagulation abnormalities, including INR >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;
- Moribund (e.g. coning, bilateral dilated unresponsive pupils), or progressively deteriorating clinical course with imminent death;
- Pregnancy (note: most patients will be beyond childbearing age);
- DIST-INFLAME sub-study: patients that use immunosuppressive or immune-modulating medication.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Surgical treatment
Minimally invasive endoscopy-guided surgery in addition to standard medical management for the treatment of spontaneous supratentorial intracerebral hemorrhage performed within 8 hours of symptom onset.
|
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.
|
No Intervention: Standard medical management
Standard medical treatment for the treatment of spontaneous supratentorial intracerebral hemorrhage (treatment of blood pressure, admission to stroke unit and supportive care, surgical treatment if necessary in case of deterioration).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
modified Rankin Scale (mRS) at 180 days
Time Frame: 180 days (±14 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.
|
180 days (±14 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
mRS at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
mRS at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
Favorable outcome, defined as a mRS of 0-2 at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
Favorable outcome, defined as a mRS of 0-2 at 180 days
Time Frame: 180 days (±14 days)
|
180 days (±14 days)
|
|
Favorable outcome, defined as a mRS of 0-2 at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
Favorable outcome, defined as a mRS of 0-3 at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
Favorable outcome, defined as a mRS of 0-3 at 180 days
Time Frame: 180 days (±14 days)
|
180 days (±14 days)
|
|
Favorable outcome, defined as a mRS of 0-3 at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
All other possible dichotomizations of the mRS at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
All other possible dichotomizations of the mRS at 180 days
Time Frame: 180 days (±14 days)
|
180 days (±14 days)
|
|
All other possible dichotomizations of the mRS at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
Death at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
Death at 180 days
Time Frame: 180 days (±14 days)
|
180 days (±14 days)
|
|
Death at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
iMTA Medical Consumption Questionnaire (iMCQ) at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
iMTA Medical Consumption Questionnaire (iMCQ) at 180 days
Time Frame: 180 days (±14 days)
|
180 days (±14 days)
|
|
iMTA Medical Consumption Questionnaire (iMCQ) at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
iMTA Productivity Cost Questionnaire (iPCQ) at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
iMTA Productivity Cost Questionnaire (iPCQ) at 180 days
Time Frame: 180 days (6 months)
|
180 days (6 months)
|
|
iMTA Productivity Cost Questionnaire (iPCQ) at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
Death within 24 hours
Time Frame: 24 hours
|
24 hours
|
|
Procedure related complications within 7 days
Time Frame: 7 days
|
7 days
|
|
Case-fatality at 7 days
Time Frame: 7 days
|
7 days
|
|
Case-fatality at 30 days
Time Frame: 30 days
|
30 days
|
|
Percentage volume reduction based at 24 hours
Time Frame: 24 hours
|
The percentage of volume reduction based on baseline CT and CT at 24 hours (in the intervention group)
|
24 hours
|
Percentage of participants with hematoma volume reduction ≥70%
Time Frame: 24 hours
|
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)
|
24 hours
|
Percentage of participants with hematoma volume reduction ≥80%
Time Frame: 24 hours
|
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)
|
24 hours
|
Percentage of participants with remaining hematoma volume ≤10mL
Time Frame: 24 hours
|
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)
|
24 hours
|
Percentage of participants with remaining hematoma volume ≤15mL
Time Frame: 24 hours
|
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)
|
24 hours
|
Conversion to craniotomy
Time Frame: 24 hours
|
The percentage of participants in which a conversion to craniotomy was required and done (in the intervention group)
|
24 hours
|
National Institute of Health Stroke Scale (NIHSS) at 6 days (±1 day)
Time Frame: 6 days (±1 day)
|
6 days (±1 day)
|
|
Barthel Index at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
Barthel Index at 180 days
Time Frame: 180 days (±14 days)
|
180 days (±14 days)
|
|
Barthel Index at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
EuroQol 5D-5L at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
EuroQol 5D-5L at 365 days
Time Frame: 180 days (±14 days)
|
180 days (±14 days)
|
|
EuroQol 5D-5L at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
Stroke-Specific Quality of Life scale at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
Stroke-Specific Quality of Life scale at 180 days
Time Frame: 180 days (±14 days)
|
180 days (±14 days)
|
|
Stroke-Specific Quality of Life scale at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
iMTA Valuation of Informal Care Questionnaire (iVICQ) at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
iMTA Valuation of Informal Care Questionnaire (iVICQ) at 180 days
Time Frame: 180 days (±14 days)
|
180 days (±14 days)
|
|
iMTA Valuation of Informal Care Questionnaire (iVICQ) at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
Home time at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
Home time at 180 days
Time Frame: 180 days (±14 days)
|
180 days (±14 days)
|
|
Home time at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
|
Patient location at 90 days
Time Frame: 90 days (±14 days)
|
90 days (±14 days)
|
|
Patient location at 180 days
Time Frame: 180 days (±14 days)
|
180 days (±14 days)
|
|
Patient location at 365 days
Time Frame: 365 days (±14 days)
|
365 days (±14 days)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Perihematomal edema at 6 days (±1 day)
Time Frame: 6 days (±1 day)
|
DIST-INFLAME sub-study: Perihematomal edema assessed on non-contrast CT at 6 days (±1 day)
|
6 days (±1 day)
|
Immune and metabolomic profiles in venous blood at 3 days
Time Frame: 3 days
|
DIST-INFLAME sub-study: Immune and metabolomic profiles in venous blood at 3 days
|
3 days
|
Immune and metabolomic profiles in venous blood at 6 days (±1 day)
Time Frame: 6 days (±1 day)
|
DIST-INFLAME sub-study: Immune and metabolomic profiles in venous blood at 6 days (±1 day)
|
6 days (±1 day)
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Catharina JM Klijn, MD PhD, Radboud University Medical Center
- Principal Investigator: Ruben Dammers, MD PhD, Erasmus Medical Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NL80112.078.22
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Intracerebral Hemorrhage
-
Wake Forest University Health SciencesActive, not recruitingStroke Hemorrhagic | Intracerebral Hemorrhage | Cerebral Edema | Intracerebral Hemorrhage, Hypertensive | Intracerebral Hemorrhage IntraparenchymalUnited States
-
Tongji HospitalUnknown
-
Huazhong University of Science and TechnologyUnknownHypertensive Intracerebral HemorrhageChina
-
Huazhong University of Science and TechnologyUnknownHypertensive Intracerebral HemorrhageChina
-
Beijing Tiantan HospitalBeijing Friendship Hospital; RenJi Hospital; Qilu Hospital of Shandong University and other collaboratorsRecruitingSpontaneous Intracerebral HemorrhageChina
-
University Hospital, Basel, SwitzerlandSwiss Heart FoundationActive, not recruitingIntracerebral Hemorrhage (ICH)Switzerland
-
University of Erlangen-Nürnberg Medical SchoolCompleted
-
AegisCN LLCCompletedIntracerebral Hemorrhage (ICH)United States
-
CellMed AG, a subsidiary of BTG plc.TerminatedIntracerebral Hemorrhage (ICH)Germany
-
Tang-Du HospitalRecruitingIntracerebral Hemorrhage;Circulating ExosomesChina
Clinical Trials on Minimally invasive endoscopy-guided surgery
-
Radboud University Medical CenterDutch Heart Foundation; Penumbra Inc.CompletedIntracerebral Hemorrhage | Surgical Procedures, Minimally InvasiveNetherlands
-
University of Illinois at ChicagoRecruiting
-
Istituto Clinico HumanitasFondazione Umberto VeronesiRecruiting
-
University of OuluRecruitingEndometriosis | Surgery | Deep EndometriosisFinland
-
National Taiwan University HospitalCompletedColorectal Cancer | AdhesionTaiwan
-
October 6 UniversityCompleted
-
Yarmouk UniversityCompletedMinimally Invasive Surgery | Hydatid Disease | Spleen-Preserving Surgery | Echinococcus Granulosus InfectionJordan
-
Hospital del MarEnrolling by invitationGallbladder CancerSpain
-
Tianjin Medical University Cancer Institute and...Harvard Medical School (HMS and HSDM); M.D. Anderson Cancer Center; Massachusetts... and other collaboratorsEnrolling by invitation
-
Yonsei UniversityRecruiting