Dutch Intracerebral Hemorrhage Surgery Trial

NCT ID: NCT05460793

Last Updated: 2024-11-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-03
• Study Completion Date: 2028-07-31

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/

Conditions

Intracerebral Hemorrhage; Minimally Invasive Surgical Procedures; Endoscopic Surgical Procedures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Minimally invasive endoscopy-guided surgery

Intervention Type: DEVICE

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.

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).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Minimally invasive endoscopy-guided surgery

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.

Intervention Type: DEVICE

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 >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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Dutch National Health Care Institute

OTHER

Sponsor Role: collaborator

Penumbra Inc.

INDUSTRY

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Catharina JM Klijn, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Ruben Dammers, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

Amsterdam University Medical Center

Amsterdam, , Netherlands

Site Status: RECRUITING

Medisch Spectrum Twente

Enschede, , Netherlands

Site Status: NOT_YET_RECRUITING

University Medical Center Groningen

Groningen, , Netherlands

Site Status: NOT_YET_RECRUITING

Leiden University Medical Center

Leiden, , Netherlands

Site Status: NOT_YET_RECRUITING

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status: RECRUITING

Radboud University Medical Center

Nijmegen, , Netherlands

Site Status: RECRUITING

Erasmus University Medical Center

Rotterdam, , Netherlands

Site Status: RECRUITING

Haaglanden Medical Center

The Hague, , Netherlands

Site Status: RECRUITING

Elisabeth-TweeSteden Hospital

Tilburg, , Netherlands

Site Status: RECRUITING

University Medical Center Utrecht

Utrecht, , Netherlands

Site Status: RECRUITING

Isala

Zwolle, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Catharina JM Klijn, MD PhD

Role: CONTACT

karin.klijn@radboudumc.nl

+31 24 361 33 94

Floor NH Wilting, MD

Role: CONTACT

floor.wilting@radboudumc.nl

+31 24 36166 00

Related Links

http://dutch-ich.nl

Website of the Dutch ICH Surgery Trial (DIST)

Other Identifiers

NL80112.078.22

Identifier Type: -

Identifier Source: org_study_id