Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study

Not Applicable

Completed

• Conditions: Surgical Procedures, Minimally Invasive; Intracerebral Hemorrhage
• Interventions: Device: Minimally-invasive endoscopy-guided surgery

• Registration Number: NCT03608423
• Lead Sponsor: Radboud University Medical Center

Brief 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).

Detailed Description

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-04-30
• Study First Submitted QC: 2018-07-23
• Study First Posted: 2018-08-01
• Study Start: 2018-12-03
• Primary Completion: 2022-04-07
• Study Completion: 2022-04-07
• Status Verified: 2022-08
• Last Update Submitted: 2022-10-11
• Last Update Posted: 2022-10-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 169

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

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Surgical treatment	Minimally-invasive endoscopy-guided surgery	Minimally-invasive endoscopy-guided surgery or hematoma aspiration, additional to standard medical treatment.

Primary Outcome Measures

Name	Time	Method
Death within 24 hours	24 hours	Death within 24 hours after baseline.
Neurological deterioration within 24 hours	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,
Proportion of volume reduction	Baseline and 24 hours (based on the comparison baseline CT and CT at 24 hours).	The proportion of volume reduction, based on baseline CT and CT at 24 hours (in the intervention group).

Secondary Outcome Measures

Name	Time	Method
Mortality at 7 days	7 days	Proportion of patients that died within 7 days after baseline
Percentage of patients with clot volume reduction ≥60%	Baseline and 24 hours CT (the difference is measured)	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)
Percentage of patients with clot volume reduction ≥ 80%	Baseline and 24 hours CT (the difference is measured)	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)
Functional outcome at 6 months	6 months (180 days)	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.
Functional outcome at 3 months	3 months (90 days)	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.
National Institute of Health Stroke Scale (NIHSS) at 7 days or discharge	7 days (or at discharge from the hospital if earlier)	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.
Procedure related complications	7 days	The proportion of patients with procedure related complications at 7 days, including: rebleed, intracranial hemorrhage, epileptic seizures and intracranial infection. (in the intervention group)
Mortality at 30 days	30 days	Proportion of patients that died within 30 days after baseline
Percentage of patients with remaining clot volume of ≤ 15mL	24 hours CT	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)
Proportion of conversion to craniotomy	24 hours	The proportion of patients in which a conversion to craniotomy was required and done. (in the intervention group)

Trial Locations

Locations (10)

Haaglanden Medical Center; 🇳🇱 Den Haag, Netherlands

Academic Medical Center; 🇳🇱 Amsterdam, Netherlands

Maastricht University Medical Center; 🇳🇱 Maastricht, Netherlands

Erasmus Medical Center; 🇳🇱 Rotterdam, Netherlands

Elisabeth Tweesteden Ziekenhuis; 🇳🇱 Tilburg, Netherlands

Medisch Spectrum Twente; 🇳🇱 Enschede, Netherlands

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Radboud University Medical Center; 🇳🇱 Nijmegen, Gelderland, Netherlands

Isala; 🇳🇱 Zwolle, Netherlands

University Medical Center Utrecht; 🇳🇱 Utrecht, Netherlands