Clinical trial NCT03608423: Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study
Official title: The Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study; Minimally-invasive Endoscopy-guided Surgery for Spontaneous Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intracerebral Hemorrhage
Surgical Procedures, Minimally Invasive
Keywords: Intracerebral Hemorrhage
Surgical Procedures, Minimally Invasive
Surgical Procedures, Endoscopic
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Heart Foundation
name: Penumbra Inc.
First posted: 2018-08-01
Enrollment: 169
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: We will include 40 patients in the surgical arm (inclusion in three hospitals) and aim for 120 matched controls in the other arm (in 7 other hospitals).
Primary purpose: TREATMENT

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

Eligibility criteria: 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).

Primary outcomes:
measure: Death within 24 hours
timeFrame: 24 hours
measure: Neurological deterioration within 24 hours
timeFrame: 24 hours
measure: Proportion of volume reduction
timeFrame: Baseline and 24 hours (based on the comparison baseline CT and CT at 24 hours).
Secondary outcomes:
measure: Procedure related complications
timeFrame: 7 days
measure: Mortality at 7 days
timeFrame: 7 days
measure: Mortality at 30 days
timeFrame: 30 days
measure: Percentage of patients with clot volume reduction ≥60%
timeFrame: Baseline and 24 hours CT (the difference is measured)
measure: Percentage of patients with clot volume reduction ≥ 80%
timeFrame: Baseline and 24 hours CT (the difference is measured)
measure: Percentage of patients with remaining clot volume of ≤ 15mL
timeFrame: 24 hours CT
measure: Proportion of conversion to craniotomy
timeFrame: 24 hours
measure: Functional outcome at 3 months
timeFrame: 3 months (90 days)
measure: Functional outcome at 6 months
timeFrame: 6 months (180 days)
measure: National Institute of Health Stroke Scale (NIHSS) at 7 days or discharge
timeFrame: 7 days (or at discharge from the hospital if earlier)
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Den Haag
country: Netherlands
facility: Haaglanden Medical Center
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Tilburg
country: Netherlands
facility: Elisabeth Tweesteden Ziekenhuis
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Zwolle
country: Netherlands
facility: Isala
Study officials:
affiliation: Erasmus Medical Center
name: Ruben Dammers, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lahr MMH, Maas WJ, van der Zee DJ, Uyttenboogaart M, Buskens E. Rationale and design for studying organisation of care for intra-arterial thrombectomy in the Netherlands: simulation modelling study. BMJ Open. 2020 Jan 7;10(1):e032754. doi: 10.1136/bmjopen-2019-032754.