Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study

Intracerebral Hemorrhage Clinical Trial

— DIST pilot  

Official title:

The Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study; Minimally-invasive Endoscopy-guided Surgery for Spontaneous Intracerebral Hemorrhage

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03608423
• Other study ID #: NL6310007817
• Status: Completed
• Phase: N/A
• Start date: December 3, 2018
• Est. completion date: April 7, 2022

Study information

• Verified date: August 2022
• Source: Radboud University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background:

Intracerebral hemorrhage (ICH) accounts for 15-20% 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 early blood pressure lowering there is currently no treatment of proven benefit. Important predictors of poor outcome are increasing age, decreasing Glasgow Coma Scale score, increasing ICH volume, presence of intraventricular hemorrhage and deep or infratentorial location. In addition, secondary injury due to development of edema and inflammatory response, contribute to disability and death. Surgical treatment, mostly comprising craniotomy, has so far not been proven effective. In the largest trials STICH and STICH II, the median time to treatment was more than 24 hours, which may be an important explanation for the lack of treatment effect.

The investigators hypothesize that early, minimally-invasive, endoscopy-guided surgery improves outcome in patients with spontaneous supratentorial ICH.

Objective: to study safety, feasibility and technical effectiveness of minimally-invasive endoscopy guided surgery for treatment of spontaneous supratentorial ICH and to estimate the potential effect on outcome.

Study design: a multicenter, prospective intervention study (phase II) with a telephonic follow up interview at 90 and 180 days.The pilot study serves as a prelude to a randomized phase III trial in which the investigators aim to assess whether this intervention improves functional outcome at 90 and 180 days.

Study population: patients with spontaneous supratentorial ICH of 18 years and older. Forty patients in three participating centers (Radboudumc, Erasmus MC and AMC) will undergo minimally-invasive endoscopy-guided surgery. Three-hundred-and-sixty patients undergoing standard medical treatment in one of 7 other participating centers, will be included as a control group.

Intervention: minimally-invasive endoscopy-guided surgery within 8 hours of symptom onset, in addition to standard medical management.

Primary study outcomes: safety (death within 24 hours, 7-day procedure related complications, 7-day mortality, 30-day mortality) and technical effectiveness (proportional volume reduction, proportion of participants with volume reduction > 60 and >80%, and proportion with remaining clot volume <15mL).

Secondary outcomes: modified Rankin Scale score at 90 and 180 days after ICH (functional outcome).

Description:

The full protocol is available at https://dutch-ich.nl/trial-protocol-and-trial-documents.html

Recruitment information / eligibility

• Status: Completed
• Enrollment: 169
• Est. completion date: April 7, 2022
• Est. primary completion date: April 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18

2. NIHSS = 2

3. Supratentorial ICH confirmed by CT, without a CT-angiography confirmed causative vascular lesion (e.g. aneurysma, arteriovenous malformation [AVM], dural arteriovenous fistula [DAVF], cerebral venous sinus thrombosis [CVST]).

4. Minimal lesion size 10 mL

5. Intervention can be started within 8 hours from symptoms onset; or for controls presentation within 8 hours of symptom onset.

6. Patient's or legal representative's written informed consent

Exclusion Criteria:

1. Pre-stroke disability, which interferes with the assessment of functional outcome at 90 days, i.e. mRS > 2

2. Causative vascular lesion (e.g. aneurysm, AVM, DAVF, CVST) on CT-angiography or other known underlying cause (e.g. tumor, cavernoma)

3. Untreated coagulation abnormalities, including INR > 1.3 (point of care measurement allowed) and treatment with oral thrombin or factor X antagonists; patients on vitamin K antagonist can be included after correction of the INR.

4. Current known severe infection for which antibiotic treatment at time of ICH symptom onset

5. Patient moribund (e.g. coning, bilateral dilated unresponsive pupils)

6. Pregnancy (note: most patients will be beyond child bearing age; if not a pregnancy test is mandatory).

Related Conditions & MeSH terms

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

Intervention

Device:
• Minimally-invasive endoscopy-guided surgery
Surgery started within 8 hours of onset of spontaneous intracerebral hemorrhage.

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam
Netherlands	Haaglanden Medical Center	Den Haag
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Radboud University Medical Center	Nijmegen	Gelderland
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	Elisabeth Tweesteden Ziekenhuis	Tilburg
Netherlands	University Medical Center Utrecht	Utrecht
Netherlands	Isala	Zwolle

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University Medical Center	Dutch Heart Foundation, Penumbra Inc.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death within 24 hours	Death within 24 hours after baseline.	24 hours
Primary	Neurological deterioration within 24 hours	Neurological deterioration, defined as an increase of =4 points on the sumscore of the NIHSS or >2 National Institutes of Health Stroke Scale (NIHSS)is a sum score, composed of 11 items, each of which scores a specific ability between 0 and 4. For each item, a score of 0 typically indicates normal function in that ability, while a higher score indicates the level of impairment. The total score varies between 0 (no symptoms at all) and 42. points on one item of NIHSS,	24 hours
Primary	Proportion of volume reduction	The proportion of volume reduction, based on baseline CT and CT at 24 hours (in the intervention group).	Baseline and 24 hours (based on the comparison baseline CT and CT at 24 hours).
Secondary	Procedure related complications	The proportion of patients with procedure related complications at 7 days, including: rebleed, intracranial hemorrhage, epileptic seizures and intracranial infection. (in the intervention group)	7 days
Secondary	Mortality at 7 days	Proportion of patients that died within 7 days after baseline	7 days
Secondary	Mortality at 30 days	Proportion of patients that died within 30 days after baseline	30 days
Secondary	Percentage of patients with clot volume reduction =60%	The proportion of patients in which the clot volume could be reduced with 60% or more, based on the comparison baseline CT and CT at 24 hours. (in the intervention group)	Baseline and 24 hours CT (the difference is measured)
Secondary	Percentage of patients with clot volume reduction = 80%	The proportion of patients in which the clot volume could be reduced with 80% or more, based on the comparison baseline CT and CT at 24 hours. (in the intervention group)	Baseline and 24 hours CT (the difference is measured)
Secondary	Percentage of patients with remaining clot volume of = 15mL	The proportion of patients in which due to clot removal a remaining clot volume of = 15mL was established at 24 hours. (in the intervention group)	24 hours CT
Secondary	Proportion of conversion to craniotomy	The proportion of patients in which a conversion to craniotomy was required and done. (in the intervention group)	24 hours
Secondary	Functional outcome at 3 months	Ordinal shift in functional outcome (comparing the intervention group to the controls), assessed with the modified Rankin Scale (mRS) at 3 months. 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.; A favorable outcome is defined as mRS 0-3 and mRS 0-2.	3 months (90 days)
Secondary	Functional outcome at 6 months	Ordinal shift in functional outcome (comparing the intervention group to the controls), , assessed with the modified Rankin Scale (mRS) at 6 months. 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.; A favorable outcome is defined as mRS 0-3 and mRS 0-2.	6 months (180 days)
Secondary	National Institute of Health Stroke Scale (NIHSS) at 7 days or discharge	National Institutes of Health Stroke Scale (NIHSS)is a sum score, composed of 11 items, each of which scores a specific ability between 0 and 4. For each item, a score of 0 typically indicates normal function in that ability, while a higher score indicates the level of impairment. The total score varies between 0 (no symptoms at all) and 42.	7 days (or at discharge from the hospital if earlier)

External Links

•   Website of the Dutch ICH Surgery Trial pilot study