Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study (DIST pilot)

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

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).

Study Overview

• Status: Completed
• Conditions: Intracerebral Hemorrhage; Surgical Procedures, Minimally Invasive
• Intervention / Treatment: Device: Minimally-invasive endoscopy-guided surgery

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 169
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center
  • Den Haag, Netherlands
    • Haaglanden Medical Center
  • Enschede, Netherlands
    • Medisch Spectrum Twente
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
  • Maastricht, Netherlands
    • Maastricht University Medical Center
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medical Center
  • Tilburg, Netherlands
    • Elisabeth TweeSteden Ziekenhuis
  • Utrecht, Netherlands
    • University Medical Center Utrecht
  • Zwolle, Netherlands
    • Isala
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GC
      • Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surgical treatment; Minimally-invasive endoscopy-guided surgery or hematoma aspiration, additional to standard medical treatment.	Device: Minimally-invasive endoscopy-guided surgery; Surgery started within 8 hours of onset of spontaneous intracerebral hemorrhage.; Other Names: Minimally-invasive endoscopy-guided hematoma aspiration
No Intervention: Standard medical management; Standard medical treatment (treatment of bloodpressure, admission to stroke unit and supportive care, surgical treatment if necessary in case of deterioration)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death within 24 hours	Death within 24 hours after baseline.	24 hours
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Mortality at 7 days	Proportion of patients that died within 7 days after baseline	7 days
Mortality at 30 days	Proportion of patients that died within 30 days after baseline	30 days
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)
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)
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
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
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)
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)
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)

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Dutch Heart Foundation; Penumbra Inc.
• Investigators: Principal Investigator: Ruben Dammers, Dr., Erasmus Medical Center

Publications and helpful links

General Publications

• 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.

Helpful Links

• Website of the Dutch ICH Surgery Trial pilot study

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Actual): April 7, 2022
• Study Completion (Actual): April 7, 2022

Study Registration Dates

• First Submitted: April 30, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Intracerebral Hemorrhage; Surgical Procedures, Minimally Invasive; Surgical Procedures, Endoscopic
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: NL6310007817

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes