A late-breaking abstract presented at the International Stroke Conference (ISC) 2021 (17–19 March, virtual) reports results from the MR CLEAN-NO IV trial, which is assessing the efficacy and safety of direct endovascular thrombectomy (EVT) compared with intravenous thrombolysis (IVT) followed by EVT in patients with acute ischaemic stroke caused by an occlusion of the anterior circulation. Researchers found no statistically significant difference in outcomes between these groups.
This study’s origins were in the first MR CLEAN trial in 2015. According to researchers, this was the first trial to demonstrate the benefit of endovascular treatment in addition to standard treatment. Researchers report a further inspiration for this study were those trials carried out in Asia, especially DIRECT-MT. DIRECT-MT was carried out in China and is the sister trial of MR CLEAN-NO IV.
Yvo Roos, co-principle investigator (PI) of MR CLEAN-NO IV and professor at the Department of Neurology at Amsterdam UMC, Amsterdam, The Netherlands, commented that the DIRECT-MT trial “Showed significant non-inferiority of direct endovascular treatment on functional outcome, and showed a tendency towards less haemorrhages with direct EVT treatment.”
The hypothesis for MR CLEAN-NO IV was that “direct EVT for patients with acute ischaemic stroke caused by an intracranial proximal large vessel occlusion in the anterior circulation is superior to IV alteplase followed by EVT in terms of functional outcome.”
The MR CLEAN-NO IV trial is a randomised, controlled, open-label, blinded–endpoint trial that included patients with acute ischaemic stroke caused by an occlusion of the anterior circulation. The first patient was enrolled in the trial in January 2018, and the last October 2020. A total of 539 patients were included across 20 stroke centres in The Netherlands, Belgium and France. Of these, 273 were allocated to direct EVT and 266 to the IVT and EVT group. No patients were lost to follow-up.
Primary outcomes were the subjects’ modified Rankin Scale (mRS) at 90 days. Secondary outcomes included mRS dichotomisations, National Institutes of Health Stroke Scale (NIHSS) score, reperfusion (on eTICI score), final infarct volume, and safety outcomes such as mortality.
Researchers found no statistically significant difference between the two groups. Primary outcomes were similar, with subjects who recorded a mRS of 0–2 in the IVT plus EVT group making up 51.1%, and in the direct EVT group, this was 49.1%. At the other end of the scale, researchers also noted no large difference between groups for patients with an mRS of 4–5, with the IVT plus EVT group having 23.7% and the direct EVT group having 20.5%.
In secondary outcomes, investigators observed one statistically significant difference in the beta of the NIHSS score, with a finding of 0.21 five to seven days after discharge. However, they found no other statistically significant difference. This remained true even in patient mortality, in the IVT plus EVT group this was 15.8%, and in the direct EVT group it was 20.5%.
Roos concluded: “We did not show superiority nor non-inferiority of direct EVT over IV alteplase followed by EVT, and we found similar haemorrhage rates with or without IV alteplase before EVT.”
Charles Majoie, co-PI of the study and professor of neuroradiology at the Amsterdam University Medical Centre (Amsterdam, The Netherlands), commented: “For now we propose to continue standard care, so IV alteplase followed by EVT for patients who are eligible for both and admitted directly to thrombectomy-capable centres, but the trial also allows for more individualised treatment in certain subgroups, for instance omitting IV alteplase in patients with carotid-T occlusions in whom EVT can start promptly. When in doubt, leave it out.”