Endovascular treatment for acute ischemic stroke in the Netherlands

ISRCTN	ISRCTN10888758
DOI	https://doi.org/10.1186/ISRCTN10888758
Secondary identifying numbers	NTR1804, NL 30557.078.10 v02, NL695

Submission date: 03/06/2012
Registration date: 24/07/2012
Last edited: 18/12/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Ischaemic strokes occur when a blood clot blocks the flow of blood to the brain. Intra-arterial thrombolysis and mechanical thrombectomy is a new and promising treatment for patients with acute ischemic stroke. This treatment involves going into the brain arteries with a very small tube (catheter) to deliver treatment at the site of the blocked blood vessel that caused the stroke, reopening the blocked vessels and removing the clot. This study will investigate the effectiveness and safety of this treatment.

Who can participate?
Patients with acute ischemic stroke who admitted to the ER of one of the participating medical centers within 6 hours from onset of symptoms.

What does the study involve?
Participants are randomly allocated to receive either standard treatment for acute ischemic stroke or intra-arterial treatment as described above. Participants then undergo additional MRI or CT scans to check whether the blocked vessel has been reopened. After 1 week, a CT scan is carried out to assess the extent of the stroke. Blood is drawn at this time to look for blood clotting abnormalities. After 3 months, participants are approached by telephone to check on their general condition.

What are the possible benefits and risks of participating?
Those who participate in the study will benefit from high level stroke assessment by experienced stroke neurologists. As the effectiveness of the treatment is not yet proven, the opportunity to receive this treatment cannot be called a benefit. The treatment is probably associated with an increased risk of bleeding inside the skull and at the site of the cather insertion in the groin. Early studies so far suggest that the risks of the treatment are in balance with the expected benefit.

Where is the study run from?
In 14 large hospitals in the Netherlands, listed on the trial website: http://www.mrclean-trial.org/centers.htm

When is the study starting and how long is it expected to run for?
December 2010 to January 2015

Who is funding the study?
The project is funded by the Dutch Heart Foundation, and by several companies, all of whom are listed on the trial website: http://www.mrclean-trial.org/sponsors.htm

Who is the main contact?
Prof. Diederik Dippel and Prof. Charles Majoie
mrclean@erasmusmc.nl

Study website

Contact information

Prof Diederik Dippel
Scientific

Erasmus MC University Medical Center Rotterdam
's-Gravendijkwal 230
PO Box 2040
Rotterdam
3000CA
Netherlands

Phone	+31 (0)10 70 43979
Email	d.dippel@erasmusmc.nl

Study information

Study design	Multicenter randomized open-label treatment and blinded endpoint evaluation (PROBE design)
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Patient information sheet can be found at: http://www.mrclean-trial.org/forms.htm (Dutch)
Scientific title	Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands
Study acronym	MR CLEAN
Study objectives	The primary objective of this study is to estimate the effect of endovascular treatment on overall functional outcome after acute ischemic stroke of less than six hour duration, in patients with a symptomatic intracranial anterior circulation occlusion.
Ethics approval(s)	Medical Ethics Committee and Resarch Board of Erasmus MC University Medical Center
Health condition(s) or problem(s) studied	Acute ischemic stroke, caused by intracranial proximal arterial occlusion (anterior circulation)
Intervention	Intervention arms consists of endovascular treatment by means of microcatheter guided local application of recombinant tissue plasminogen activator (rt-PA) or urokinase, and/or mechanical thrombectomy, by means of a retraction device, aspiration device, or retrievable stent. The control arm consists of regular treatment according to current national clinical guidelines.
Intervention type	Procedure/Surgery
Primary outcome measure	Score on the modified Rankin scale at 3 months
Secondary outcome measures	Imaging parameters: 1. Vessel recanalization at 24 hours after treatment, assessed by CTA or MRA. The criteria for recanalization on CTA or MRA are based on a simplified TICI score (Table 5b),45 and the clot burden score, proposed by Puetz et al (Table 5c)46. 2. Infarct size assessed by CT on day 5-7, using standard methods, including manual tracing of the infarct perimeter and semiautomated pixel thresholding.47, 48 Infarct size at day 5-7 will be compared with plain CT and perfusion CT results (if available) at baseline. 3. CTA or MRA at 24 hours will be compared with baseline vessel imaging data, to estimate the recanalization rate. Perfusion CT at baseline is optional, but available at most centers. Clinical parameters: 1. NIHSS, including NIH supplemental motor score, 50 at 24 hours 2. NIHSS at 1 week or at discharge. Functional outcome: 1. Score on the EQ5D at 90 days 2. Barthel index at 90 days
Overall study start date	01/12/2010
Completion date	01/01/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	500
Key inclusion criteria	1. A clinical diagnosis of acute stroke, with a deficit on the National Institutes of Health (NIH) stroke scale of 2 points or more 2. Computerised tomography (CT) or magnetic resonance imaging (MRI) scan ruling out intracranial hemorrhage 3. Intracranial arterial occlusion of the distal intracranial carotid artery or middle (M1/M2) or anterior (A1/A2) cerebral artery, demonstrated with Computed Tomography Angiography (CTA), magnetic resonance angiography (MRA), Digital subtraction angiography (DSA) or transcranial Doppler/duplex (TCD) 4. The possibility to start treatment within 6 hours from onset 5. Informed consent given 6. Age 18 or over
Key exclusion criteria	General: 1. Arterial blood pressure > 185/110 mmHg 2. Blood glucose < 2.7 or > 22.2 mmol/L 3. Intravenous treatment with thrombolytic therapy in a dose exceeding 0.9 mg/kg alteplase or 90 mg 4. Intravenous treatment with thrombolytic therapy despite contra-indications, i.e. major surgery, gastrointestinal bleeding or urinary tract bleeding within the previous 2 weeks, or arterial puncture at a non-compressible site within the previous 7 days For Intended mechanical thrombectomy: Laboratory evidence of coagulation abnormalities, i.e. platelet count <40 x 109/L, activated partial thromboplastin time (APTT)>50 sec or International Normalised Ratio (INR) >3.0. For intended intra-arterial thrombolysis: 1. Cerebral infarction in the distribution of the relevant occluded artery in the previous 6 weeks 2. History of intracerebral hemorrhage 3. Severe head injury (contusion) in the previous 4 weeks 4. Clinical or laboratory evidence of coagulation abnormalities, i.e. platelet count <90 x 109/L, APTT>50 sec or INR >1.7
Date of first enrolment	01/12/2010
Date of final enrolment	01/01/2015

Locations

Countries of recruitment

Netherlands

Study participating centre

Erasmus MC University Medical Center Rotterdam

Rotterdam
3000CA
Netherlands

Sponsor information

Dutch Heart Foundation (Netherlands)
Charity

Prinses Catharina Amaliastraat 10
The Hague
2496 XD
Netherlands

Phone	+31 (0)70 31 55555
Email	info@hartstichting.nl
Website	http://www.hartstichting.nl
"ROR"	https://ror.org/05nxhgm70

Funders

Funder type

Charity

Dutch Heart Foundation (Nederlandse Hartstichting) (Netherlands) ref: 2008T030
Private sector organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): Heart Foundation
Location: Netherlands

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	01/09/2014		Yes	No
Results article	results	01/01/2015		Yes	No
Results article	results	01/03/2016		Yes	No
Results article	results	01/06/2016		Yes	No
Results article	results	16/08/2016		Yes	No
Results article	results	01/09/2016		Yes	No
Results article	results	01/10/2016		Yes	No
Results article	results	01/12/2016		Yes	No
Results article	results	06/04/2017		Yes	No
Results article	results	01/05/2017		Yes	No
Results article	results	01/05/2017		Yes	No
Results article	results	20/06/2017		Yes	No
Results article	results	01/07/2017		Yes	No
Results article	results	01/10/2017		Yes	No
Results article	results	01/02/2018		Yes	No
Results article	results	01/02/2018		Yes	No
Results article	results	01/02/2018		Yes	No
Results article	results	01/03/2018		Yes	No
Results article	results	01/04/2018		Yes	No
Results article	results	01/12/2018		Yes	No
Results article	results	01/05/2019		Yes	No
Other publications	post hoc analysis	01/12/2019	12/12/2019	Yes	No
Abstract results	Economic evaluation	14/10/2021	15/10/2021	No	No
Other publications	retrospective analysis	08/06/2022	09/06/2022	Yes	No
Abstract results	Results abstract European Stroke Organisation Conference 2021	03/09/2021	29/03/2023	No	No
Results article	Multivessel occlusions (MVO)	15/12/2023	18/12/2023	Yes	No

Editorial Notes

18/12/2023: Publication reference added.
29/03/2023: Abstract added.
09/06/2022: Publication reference added.
15/10/2021: The following changes have been made:
1. Publication reference added.
2. NL695 has been added to the protocol/serial numbers.
12/12/2019: Publication reference added.
21/12/2018: Publication reference added.
10/10/2018: Publication reference added.
31/01/2018: Publication reference added.
30/01/2018: Publication reference added.
20/10/2017: Publication reference added.
19/10/2017: Publication references added.
28/04/2017: Publication reference added.
25/04/2017: Publication reference added.
24/04/2017: Publication reference added.
10/04/2017: Publication reference added.
30/03/2017: Publication reference added.
08/09/2016: Publication reference added.
22/08/2016: Publication reference added.
08/08/2016: Publication reference added.
20/07/2016: Publication reference added.
16/06/2016: Publication reference added.