NCT05460793

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. 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. 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. 3.Compare immune profiles over time in peripheral venous blood between surgically treated patients and controls (DIST-INFLAME);
  4. 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
600

participants targeted

Target at P75+ for not_applicable

Timeline
26mo left

Started Nov 2022

Longer than P75 for not_applicable

Geographic Reach
1 country

11 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress62%
Nov 2022Jul 2028

First Submitted

Initial submission to the registry

July 12, 2022

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 15, 2022

Completed
4 months until next milestone

Study Start

First participant enrolled

November 3, 2022

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2027

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2028

Last Updated

November 21, 2024

Status Verified

November 1, 2024

Enrollment Period

4.7 years

First QC Date

July 12, 2022

Last Update Submit

November 18, 2024

Conditions

Keywords

Intracerebral HemorrhageSurgical Procedures, Minimally InvasiveSurgical Procedures, Endoscopic

Outcome Measures

Primary Outcomes (1)

  • 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.

    180 days (±14 days)

Secondary Outcomes (49)

  • mRS at 90 days

    90 days (±14 days)

  • mRS at 365 days

    365 days (±14 days)

  • Favorable outcome, defined as a mRS of 0-2 at 90 days

    90 days (±14 days)

  • Favorable outcome, defined as a mRS of 0-2 at 180 days

    180 days (±14 days)

  • Favorable outcome, defined as a mRS of 0-2 at 365 days

    365 days (±14 days)

  • +44 more secondary outcomes

Other Outcomes (3)

  • Perihematomal edema at 6 days (±1 day)

    6 days (±1 day)

  • Immune and metabolomic profiles in venous blood at 3 days

    3 days

  • Immune and metabolomic profiles in venous blood at 6 days (±1 day)

    6 days (±1 day)

Study Arms (2)

Surgical treatment

EXPERIMENTAL

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.

Device: Minimally invasive endoscopy-guided surgery

Standard medical management

NO INTERVENTION

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).

Interventions

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.

Surgical treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Amsterdam University Medical Center

Amsterdam, Netherlands

RECRUITING

Medisch Spectrum Twente

Enschede, Netherlands

NOT YET RECRUITING

University Medical Center Groningen

Groningen, Netherlands

NOT YET RECRUITING

Leiden University Medical Center

Leiden, Netherlands

NOT YET RECRUITING

Maastricht University Medical Center

Maastricht, Netherlands

RECRUITING

Radboud University Medical Center

Nijmegen, Netherlands

RECRUITING

Erasmus University Medical Center

Rotterdam, Netherlands

RECRUITING

Haaglanden Medical Center

The Hague, Netherlands

RECRUITING

Elisabeth-TweeSteden Hospital

Tilburg, Netherlands

RECRUITING

University Medical Center Utrecht

Utrecht, Netherlands

RECRUITING

Isala

Zwolle, Netherlands

RECRUITING

Related Publications (1)

  • Wilting FNH, Wolsink A, Colmer NHC, Schreuder FHBM, Brouwers HB, Boogaarts HD, Dippel DWJ, Hannink G, Jolink WMT, Verbaan D, Wermer MJH, Dammers R, Klijn CJM. The Dutch Intracerebral Haemorrhage Surgery Trial: study protocol for a randomised clinical trial of minimally invasive endoscopy-guided surgery in patients with spontaneous, supratentorial intracerebral haemorrhage. Eur Stroke J. 2026 Jan 1;11(1):aakaf008. doi: 10.1093/esj/aakaf008.

Related Links

MeSH Terms

Conditions

Cerebral Hemorrhage

Condition Hierarchy (Ancestors)

Intracranial HemorrhagesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Catharina JM Klijn, MD PhD

    Radboud University Medical Center

    PRINCIPAL INVESTIGATOR
  • Ruben Dammers, MD PhD

    Erasmus Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Catharina JM Klijn, MD PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: prospective, randomized, open, blinded endpoint (PROBE) clinical trial
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 12, 2022

First Posted

July 15, 2022

Study Start

November 3, 2022

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

July 1, 2028

Last Updated

November 21, 2024

Record last verified: 2024-11

Data Sharing

IPD Sharing
Will share

De-identified data may be shared with other parties to maximize the usefulness of the collected research data. Data can be requested from the principal investigators with a detailed description of the objectives and methods of the study for which the data is intended. Data will be made available for this purpose at least 18 months after the publication of the main report. Data may also be shared with non-commercial parties for scientific purposes, including individual patient meta-analyses, and with the commercial parties involved in this study as manufacturers of minimally invasive neuronavigation integrated endoscopy-guided devices. For these purposes, specific consent will be asked from the participants. In addition, specific consent will be asked for sharing of de-identified data outside of the European Union.

Time Frame
at least 18 months after the publication of the main report.
Access Criteria
Written proposals will be assessed by DIST investigators for appropriateness of use, and a data sharing agreement in accordance with Dutch regulations will be put in place before data is shared.

Locations