Dutch Intracerebral Hemorrhage Surgery Trial

Intracerebral Hemorrhage Clinical Trial

— DIST  

Official title:

Dutch ICH Surgery Trial; Minimally Invasive Endoscopy-guided Surgery for Spontaneous Supratentorial Intracerebral Hemorrhage

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05460793
• Other study ID #: NL80112.078.22
• Status: Recruiting
• Phase: N/A
• Start date: November 3, 2022
• Est. completion date: April 2027

Study information

• Verified date: October 2023
• Source: Radboud University Medical Center
• Contact: Catharina JM Klijn, MD PhD
• Phone: +31 24 361 33 94
• Email: karin.klijn[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: April 2027
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage
• Minimally Invasive Surgical Procedures

Intervention

Device:
• 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.

Locations

Country	Name	City	State
Netherlands	Amsterdam University Medical Center	Amsterdam
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	Erasmus University Medical Center	Rotterdam
Netherlands	Haaglanden Medical Center	The Hague
Netherlands	Elisabeth-TweeSteden Hospital	Tilburg
Netherlands	University Medical Center Utrecht	Utrecht
Netherlands	Isala	Zwolle

Sponsors (4)

Lead Sponsor	Collaborator
Radboud University Medical Center	Dutch National Health Care Institute, Penumbra Inc., ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Perihematomal edema at 6 days (±1 day)	DIST-INFLAME sub-study: Perihematomal edema assessed on non-contrast CT at 6 days (±1 day)	6 days (±1 day)
Other	Immune and metabolomic profiles in venous blood at 3 days	DIST-INFLAME sub-study: Immune and metabolomic profiles in venous blood at 3 days	3 days
Other	Immune and metabolomic profiles in venous blood at 6 days (±1 day)	DIST-INFLAME sub-study: Immune and metabolomic profiles in venous blood at 6 days (±1 day)	6 days (±1 day)
Primary	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	mRS at 90 days		90 days (±14 days)
Secondary	mRS at 365 days		365 days (±14 days)
Secondary	Favorable outcome, defined as a mRS of 0-2 at 90 days		90 days (±14 days)
Secondary	Favorable outcome, defined as a mRS of 0-2 at 180 days		180 days (±14 days)
Secondary	Favorable outcome, defined as a mRS of 0-2 at 365 days		365 days (±14 days)
Secondary	Favorable outcome, defined as a mRS of 0-3 at 90 days		90 days (±14 days)
Secondary	Favorable outcome, defined as a mRS of 0-3 at 180 days		180 days (±14 days)
Secondary	Favorable outcome, defined as a mRS of 0-3 at 365 days		365 days (±14 days)
Secondary	All other possible dichotomizations of the mRS at 90 days		90 days (±14 days)
Secondary	All other possible dichotomizations of the mRS at 180 days		180 days (±14 days)
Secondary	All other possible dichotomizations of the mRS at 365 days		365 days (±14 days)
Secondary	National Institute of Health Stroke Scale (NIHSS) at 6 days (±1 day)		6 days (±1 day)
Secondary	Death at 90 days		90 days (±14 days)
Secondary	Death at 180 days		180 days (±14 days)
Secondary	Death at 365 days		365 days (±14 days)
Secondary	Barthel Index at 90 days		90 days (±14 days)
Secondary	Barthel Index at 180 days		180 days (±14 days)
Secondary	Barthel Index at 365 days		365 days (±14 days)
Secondary	EuroQol 5D-5L at 90 days		90 days (±14 days)
Secondary	EuroQol 5D-5L at 365 days		180 days (±14 days)
Secondary	EuroQol 5D-5L at 365 days		365 days (±14 days)
Secondary	Stroke-Specific Quality of Life scale at 90 days		90 days (±14 days)
Secondary	Stroke-Specific Quality of Life scale at 180 days		180 days (±14 days)
Secondary	Stroke-Specific Quality of Life scale at 365 days		365 days (±14 days)
Secondary	iMTA Medical Consumption Questionnaire (iMCQ) at 90 days		90 days (±14 days)
Secondary	iMTA Medical Consumption Questionnaire (iMCQ) at 180 days		180 days (±14 days)
Secondary	iMTA Medical Consumption Questionnaire (iMCQ) at 365 days		365 days (±14 days)
Secondary	iMTA Productivity Cost Questionnaire (iPCQ) at 90 days		90 days (±14 days)
Secondary	iMTA Productivity Cost Questionnaire (iPCQ) at 180 days		180 days (6 months)
Secondary	iMTA Productivity Cost Questionnaire (iPCQ) at 365 days		365 days (±14 days)
Secondary	iMTA Valuation of Informal Care Questionnaire (iVICQ) at 90 days		90 days (±14 days)
Secondary	iMTA Valuation of Informal Care Questionnaire (iVICQ) at 180 days		180 days (±14 days)
Secondary	iMTA Valuation of Informal Care Questionnaire (iVICQ) at 365 days		365 days (±14 days)
Secondary	Home time at 90 days		90 days (±14 days)
Secondary	Home time at 180 days		180 days (±14 days)
Secondary	Home time at 365 days		365 days (±14 days)
Secondary	Patient location at 90 days		90 days (±14 days)
Secondary	Patient location at 180 days		180 days (±14 days)
Secondary	Patient location at 365 days		365 days (±14 days)
Secondary	Death within 24 hours		24 hours
Secondary	Procedure related complications within 7 days		7 days
Secondary	Case-fatality at 7 days		7 days
Secondary	Case-fatality at 30 days		30 days
Secondary	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)	24 hours
Secondary	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)	24 hours
Secondary	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)	24 hours
Secondary	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)	24 hours
Secondary	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)	24 hours
Secondary	Conversion to craniotomy	The percentage of participants in which a conversion to craniotomy was required and done (in the intervention group)	24 hours

External Links

•   Website of the Dutch ICH Surgery Trial (DIST)