Condition category
Circulatory System
Date applied
21/09/2017
Date assigned
11/12/2017
Last edited
11/12/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

Contact information

Type

Scientific

Primary contact

Mr Robert-Jan Goldhoorn

ORCID ID

Contact details

P. Debyelaan 25
Maastricht
6229 HX
Netherlands

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

Sponsor information

Organisation

Maastricht University Medical Center

Sponsor details

P. Debyelaan 25
Maastricht
6229 HX
Netherlands

Sponsor type

Hospital/treatment centre

Website

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

Publication citations

Additional files

Editorial Notes