Plain English Summary
Background and study aims
Ischaemic strokes occur when a blood clot blocks the flow of blood and oxygen to the brain. They occur about 20,000 times a year in the Netherlands. Since the mid-nineties, ischemic stroke has been treated with clot-dissolving medication (thrombolytics) within 4.5 hours after symptoms start. This treatment has a moderate effect on clinical improvement. A new, promising treatment option and important subject of research in the past 10 years is endovascular treatment (EVT). This involves removing the clot using a small tube (catheter). This method has been proved to be safe and effective if performed within 6 hours after the start of symptoms. However, many patients with ischemic stroke (up to 25%) arrive in the hospital after this 6 hour time-window. The aim of this study is to determine the safety and effectiveness of EVT between 6 and 24 hours after the start of symptoms.
Who can participate?
Patients aged 18 or older with acute ischemic stroke
What does the study involve?
Participants are randomly allocated to be treated with EVT or the best medical treatment. Every participant undergoes a scan of the brain blood vessels to assess the restoration of blood flow 24 hours later, and a brain scan to assess final infarct (dead tissue) volume 5-7 days later. Three months later all participants are interviewed by telephone to assess their functional outcome.
What are the possible benefits and risks of participating?
EVT may improve functional outcome when applied 6 to 24 hours after the start of symptoms. Based on previous studies, few complications are expected.
Where is the study run from?
1. Maastricht University Medical Center (Netherlands)
2. Academic Medical Center (Netherlands)
3. Erasmus Medical Center (Netherlands)
4. University Medical Center Utrecht (Netherlands)
When is the study starting and how long is it expected to run for?
May 2017 to November 2022
Who is funding the study?
Dutch Heart Foundation (Netherlands)
Who is the main contact?
Robert-Jan Goldhoorn
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NL58246.078.17
Study information
Scientific title
Multicenter randomised clinical trial of endovascular treatment of acute ischemic stroke in the Netherlands for late arrivals
Acronym
MR CLEAN-LATE
Study hypothesis
Endovascular treatment for acute ischemic stroke due to an intracranial large vessel occlusion of the anterior circulation is effective for patients treated between 6 and 24 hours after symptom onset or last seen well less than 24 hours, after selection based on collateral flow.
Ethics approval
Medisch Ethische Toetsings Commissie Erasmus MC (Medical Ethical Committee Erasmus MC), 11/09/2017, ref: MEC-2017-367
Study design
Multicenter phase III clinical trial with randomized treatment allocation, open label treatment and blinded endpoint evaluation (PROBE design)
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Acute ischemic stroke due to an intracranial large vessel occlusion of the anterior circulation
Intervention
Randomisation: web-based; permuted blocks. Backup by telephone.
The control group will receive best medical management. The intervention group will receive endovascular treatment (EVT). All patients in the intervention group will be transferred to the angiosuite. The procedure involves arterial catheterization, after which intracranial thrombectomy will be performed with a stent-retriever or other device approved by the steering committee. Every participant will undergo a CTA of the cerebral vessels to assess rate of recanalization 24 hours after randomization, and a brain scan to assess final infarct volume 5-7 days after randomization. Three months after inclusion all participants will be interviewed by telephone to determine functional outcome.
Intervention type
Procedure/Surgery
Phase
Drug names
Primary outcome measures
Functional outcome, measured by the modified Rankin Scale (mRS) at 90 days
Secondary outcome measures
1. Mortality at 90 days
2. Recanalization on CTA at 24 hours
3. Infarct size on non-contrast head CT (NCCT) at 5-7 days or just before discharge
4. Symptomatic intra-cranial hemorrhage according to the Heidelberg criteria at 24 hours, and 5-7 days after randomization
5. Clinical stroke severity, measured by the National Institutes of Health Stroke Scale score at 24 hours and 5-7 days after randomization
Overall trial start date
01/05/2017
Overall trial end date
01/11/2022
Reason abandoned
Eligibility
Participant inclusion criteria
1. Clinical diagnosis of acute ischemic stroke
2. Caused by proximal intracranial anterior circulation occlusion (distal intracranial carotid artery or middle (M1/M2) cerebral artery confirmed by neuro-imaging (CTA or MRA)
3. Presence of poor*, moderate or good collateral flow as shown by neuroimaging (CTA)
4. CT or MRI ruling out intracranial hemorrhage
5. Start of IA treatment (groin puncture) possible between 6 and 24 hours after symptom onset or last seen well < 24 hours including wake-up strokes
6. A score of at least 2 on the NIH Stroke Scale
7. Age of 18 years or older
*Inclusion and randomization will be restricted to patients with moderate or good collaterals when 100 patients with poor collaterals have been included in the study
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
500
Participant exclusion criteria
1. Pre-stroke disability which interferes with the assessment of functional outcome at 90 days, i.e. mRS >2
2. Cerebral infarction in the previous 6 weeks with residual neurological deficit or signs of large recent infarction on neuroimaging in the territory of the middle cerebral antery
3. Clinical evidence of hemorrhagic diathesis, confirmed by an INR > 3 and/or a platelet count < 40 x 109/L and/or an APTT > 50 sec
4. Clearly demarcated hypodensity in >1/3 of the middle cerebral artery territory, consistent with current symptoms
5. Participation in trials other than current and MR ASAP
Recruitment start date
01/11/2017
Recruitment end date
01/11/2021
Locations
Countries of recruitment
Netherlands
Trial participating centre
Maastricht University Medical Center
Maastricht
6202 AZ
Netherlands
Trial participating centre
Academic Medical Center
Amsterdam
1005 AZ
Netherlands
Trial participating centre
Erasmus Medical Center
Rotterdam
3000 CA
Netherlands
Trial participating centre
University Medical Center Utrecht
Utrecht
3508 GA
Netherlands
Funders
Funder type
Charity
Funder name
Hartstichting
Alternative name(s)
Dutch Heart Foundation
Funding Body Type
private sector organisation
Funding Body Subtype
foundation
Location
Netherlands
Results and Publications
Publication and dissemination plan
Additional documents (study protocol/statistical analysis plan) will be available approximately 1 year after the first patient’s inclusion. Planned publication of the results in a high-impact peer-reviewed journal.
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
01/11/2023
Participant level data
To be made available at a later date
Results - basic reporting
Publication summary