Published MR CLEAN Trial Data Show Benefit of Intra-arterial Treatment for Acute Ischemic Stroke
December 17, 2014—MR CLEAN, a randomized trial of intra-arterial treatment for acute ischemic stroke, was published by Olvert A. Berkhemer, MD, et al online ahead of print in The New England Journal of Medicine (NEJM).
From their findings, the MR CLEAN investigators concluded that in patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intra-arterial treatment administered within 6 hours after stroke onset was effective and safe.
The investigators stated that the background of the study is that in patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intra-arterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking.
As summarized in NEJM, MR CLEAN was a pragmatic, phase 3, multicenter clinical trial with randomized treatment-group assignments, open-label treatment, and blinded endpoint evaluation. Intra-arterial treatment (intra-arterial thrombolysis, mechanical treatment, or both) plus usual care (which could include intravenous administration of alteplase) was compared with usual care alone (control group) in patients with acute ischemic stroke and a proximal intracranial arterial occlusion of the anterior circulation that was confirmed on vessel imaging.
The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intra-arterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis).
The investigators enrolled 500 patients at 16 medical centers in the Netherlands (233 assigned to intra-arterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intra-arterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.3). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage, reported the investigators.
The MR CLEAN trial was led by Diederik W.J. Dippel, MD, and funded by the Dutch Heart Foundation and others. For additional information, the MR CLEAN trial’s website is www.mrclean-trial.org. The MR CLEAN Netherlands Trial Registry number is NTR1804, and the Current Controlled Trials number is ISRCTN10888758.
An editorial by Professor Werner Hacke, MD, also published online ahead of print in NEJM, considered the implications of the MR CLEAN trial. Professor Hacke is Chairman, Department of Neurology, at University Hospital Heidelberg of Ruprecht-Karls University Heidelberg in Germany.
He noted that the success of enrollment of 500 patients in 3 years in a country of 16.8 million people can be attributed to the well-established network of investigator-initiated stroke trials in the Netherlands and the relative proximity of the trial’s 15 intervention centers. But more importantly, the success is the result of the Dutch government’s decision to pay for the use of thrombectomy devices only in the context of a randomized trial, thereby precluding treatment outside the trial. Professor Hacke commented, “This policy may be difficult to implement in other health systems, but imagine what progress the medical-device field would see if this strategy were the rule.”
In summary, Professor Hacke stated, “It is premature to conclude that there is no longer equipoise regarding thrombectomy. We need and will get results from other well-designed trials, not only to confirm or refute the results of MR CLEAN but also to look at effects in subgroups (according to stroke severity, occlusion site, or time to treatment initiation), for which most single trials are underpowered. MR CLEAN is the first step in the right direction.”