Endovascular treatment (EVT) has come a long way before being established as a first line treatment option for acute ischemic stroke patients with intracranial large vessel occlusion. The first clinical study from 1988, revealed a new approach towards occluded intracranial arteries by infusing thrombolytic medication at the thrombus site. Since then, the technique of EVT has developed into mechanical ways to remove the thrombus, primarily by means of a stent retriever. Selection of patients for EVT by CT-angiography, and increased awareness regarding fast referral and treatment, improved the efficacy of EVT.

In the Netherlands, the first centre started performing EVT in 2002, and by 2010 several Dutch intervention centres performed EVT. At that time EVT was considered an experimental treatment option and was not recommended in our stroke guideline. The reason for this was that although promising technical results were achieved (i.e. higher reperfusion rates compared to standard treatment), the most important question remained unanswered: does EVT improve functional recovery in patients with acute stroke?

The multicentre randomized clinical trial of endovascular treatment for acute ischemic stroke in the Netherlands (MR CLEAN) started in 2010 to answer this question. Sixteen centres participated and provided an adequate research environment with good regional coverage, 24/7 availability of CT-angiography (CTA), and 24/7 delivery of the treatment. Within three years after the start of the trial nationwide, inclusion in the trial was supported by the government which allowed reimbursement of EVT only to centres participating in the MR CLEAN trial. In 2014, MR CLEAN was the first randomized clinical trial showing functional improvement of patients who underwent EVT. Its success was based on the selection of patients with CTA, the availability of the new retrievable stents, and the enthusiastic collaboration of all centres in the Netherlands. Although several other large clinical trials subsequently confirmed these results, the broadest criteria for patient inclusion were used in MR CLEAN, which resulted in a wide implementation of EVT without the need for selection of patients based on advanced imaging other than CTA.

After the MR CLEAN trial ended, the Dutch trial centres continued their collaboration in the MR CLEAN Registry. This prospective, nationwide registry included all patients who received EVT in the Netherlands from April 2014 onwards. The registry is supported by a small research grant and by the leading academic centres. It depends on the efforts of many doctors and nurses who are aware of its importance. A recently published analysis of patients with anterior circulation acute ischemic stroke, included in MR CLEAN Registry between April 2014 and June 2016 , showed that EVT in clinical practice was at least as effective and safe as in the setting of a randomized clinical trial. The wide national implementation of EVT in Dutch clinical practice is illustrated by a large increase of procedures (approximately 200 EVT-procedures in 2014 to more than 1250 in 2016). More than half of these patients were referred from non-EVT hospitals that started to implement CT-angiography as standard diagnostic work-up for acute stroke patients, Finally, the time from onset to EVT was substantially reduced in the MR CLEAN Registry, indicating improved workflow.

In the Netherlands, the MR CLEAN trial has not only demonstrated the positive effect of EVT, but appears very useful in creating nationwide awareness, and preparing an infrastructure to adequately deliver EVT. This process was fostered by the Dutch society of Neurology and the Dutch society of Radiology which jointly defined criteria for centres that perform stroke workup, centres that perform EVT, as well as criteria for EVT interventionists. The quality criteria for non-EVT centres include 24/7 availability of IV thrombolytic treatment and CTA.  The collaboration between hospitals was key in achieving successful implementation and continued stroke-research in the Netherlands. As a follow-up to MR CLEAN, the Dutch Heart Foundation, Dutch Brain Foundation and Health~Holland as well as industry partners now support The ‘Collaboration of New Treatments of Acute Stroke’ (CONTRAST) Consortium.This collaboration is harbouring three ongoing randomised clinical trials, which aim to answer new clinical questions: MR CLEAN-NO-IV aims to clarify the consequences of omitting intravenous thrombolysis prior to EVT, MR CLEAN-MED aims to elucidate the value of per procedural addition of antithrombotic medication, and MR CLEAN-LATE aims to investigate the effect of EVT in the late time window (6-24 hours), applying collateral score in patient selection (www.contrast-consortium.nl).

Now that EVT is established in clinical practice, future research will focus on improving its efficacy and finding all patients who may benefit from this new treatment.

Ivo Jansen is a PhD-candidate in radiology at the Academic Medical Center Amsterdam, and was a coordinator of the MR CLEAN Registry between 2014 and 2017. 

Maxim Mulder recently completed his PhD on “Endovascular treatment for acute ischemic stroke” and was a coordinator of the MR CLEAN Registry between 2015 and 2017, and is currently working in clinical practice as Neurology resident.

Robert-Jan Goldhoorn is a PhD-student at Maastricht University Medical Center and one of the coordinators of MR CLEAN Registry since 2016. He is also one of the coordinating researchers of the recently started MR CLEAN-LATE study within CONTRAST (Consortium for New Treatments of Acute Stroke).

Aad van der Lugt is professor of neuroradiology and head and neck radiology at the Department of Radiology & Nuclear Medicine of the Erasmus MC, University Medical Center Rotterdam, the Netherlands. He was Co-PI of the original MR CLEAN trial. He is Co-PI of the MR CLEAN Registry, and the MR CLEAN-MED study within CONTRAST (Consortium for New Treatments of Acute Stroke).

Yvo Roos is professor of neurology and head of the department of neurology at the Academic Medical center Amsterdam. He was Co-PI of the original MR CLEAN trial. He was also Co-PI of the CLOT-MR CLEAN trial, the study which investigated the long-term follow-up and pharmaco-economics of IAT. Currently he is Co-PI of the MR CLEAN Registry, and the MR CLEAN NO-IV study within CONTRAST (Consortium for New Treatments of Acute Stroke).

Robert van Oostenbrugge is professor of neurology and head of the department of neurology at Maastricht University Medical Center, the Netherlands. He was Co-PI of the original MR CLEAN trial. He is Co-PI of the MR CLEAN Registry, and the MR CLEAN-LATE study within CONTRAST (Consortium for New Treatments of Acute Stroke).

Wim van Zwam is neuro interventionist in the Maastricht University Medical Center. He was Co-PI of the original MR CLEAN trial. He is Co-PI of the MR CLEAN Registry and the recently started MR CLEAN-LATE study within CONTRAST (Consortium for New Treatments of Acute Stroke).

Charles Majoie is professor of neuroradiology at the department of radiology, Academic Medical Center, Amsterdam, University of Amsterdam. He was Co-PI of the original MR CLEAN trial. He is Co-PI of the MR CLEAN Registry and the MR CLEAN NO-IV study, and is Co-Research Leader of CONTRAST (Consortium for New Treatments of Acute Stroke).

Diederik Dippel is professor of neurology at the department of neurology, Erasmus MC, University Medical Center Rotterdam, the Netherlands. He was Co-PI of the original MR CLEAN trial. He is Co-PI of the MR CLEAN Registry and the MR CLEAN MED study, and is Co-Research Leader of CONTRAST (Consortium for New Treatments of Acute Stroke).

Competing interests: Please see full details in the research paper.