Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands - MR CLEAN

Contribution To Literature:

The MR CLEAN trial showed that intra-arterial treatment of acute ischemic stroke led to a lower modified Rankin scale score (less disability).

Description:

The goal of the MR CLEAN trial was to evaluate intra-arterial treatment plus usual care compared with usual care alone among patients with acute ischemic stroke due to proximal artery occlusion of the anterior cerebral circulation.

Study Design

Subjects who presented within 6 hours of symptom onset of an acute ischemic stroke were randomized to intra-arterial treatment (n = 233) versus usual care (n = 267). Subjects randomized to intra-arterial treatment could receive intra-arterial thrombolysis, mechanical treatment (thrombectomy, wire disruption, or retrievable stent), or both. Of those who received intra-arterial treatment, 20% underwent general anesthesia and 80% underwent nongeneral anesthesia.

Inclusion criteria:

  • Subjects ≥18 years of age with acute ischemic stroke due to proximal artery occlusion of the anterior cerebral circulation
  • Initiation of intra-arterial treatment had to take place within 6 hours of symptom onset
  • Confirmation of anterior cerebral circulation occlusion by brain imaging (computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography)
  • Total number of enrollees: 500
  • Duration of follow-up: 90 days, 2 years
  • Mean patient age: 66 years
  • Percentage female: 42%
  • Percentage diabetics: 15%

Principal Findings:

Overall, 500 subjects were enrolled. The median age was 66 years, 58% were men, 12% had prior ischemic stroke, 28% had atrial fibrillation, 15% had diabetes mellitus, mean systolic blood pressure was 146 mm Hg, and 85% received intravenous alteplase before randomization. The median time from symptom onset to randomization was 204 minutes. The time from symptom onset to start of intra-arterial treatment was 4:01 hours among those who received general anesthesia versus 3:40 hours among those who received nongeneral anesthesia (p = 0.02).

The location of stroke was the intracranial internal carotid artery in <1%, the internal carotid artery with involvement of the M1 middle cerebral artery segment in 25%, the M1 middle cerebral artery segment in 66%, the M2 middle cerebral artery segment in 8%, or the A1 or A2 anterior cerebral artery segment in <1%.

In the treatment group, retrievable stents were used in 82% and other devices in 2%. Additional intra-arterial thrombolytic therapy was used in 10%, whereas intra-arterial thrombolytic therapy was used as monotherapy in <1%.

The primary outcome, the median modified Rankin scale score at 90 days, was 3 in the intervention group versus 4 in the control group (adjusted odds ratio, 1.67; 95% confidence interval, 1.21-2.30). Among those who underwent nongeneral anesthesia, there was a suggestion of good clinical outcome (adjusted odds ratio, 1.6; 95% confidence interval, 0.98-2.54). Baseline systolic blood pressure displayed a U-shaped relationship with poor functional outcome (systolic blood pressure of approximately 120 mm Hg was associated with the best functional outcome). However, correlation of systolic blood pressure with functional outcome and intracranial hemorrhage was similar between treatment groups.

The median modified Rankin scale score at 2 years, was 3 in the intervention group versus 4 in the control group (adjusted odds ratio, 1.68; 95% confidence interval, 1.15-2.45).

Secondary outcomes:

  • Death at 30 days: 19% vs. 18%, respectively, for treatment vs. control
  • Mortality at 2 years: 26.0% vs. 31.0%, respectively, for treatment vs. control
  • Any intra-cerebral hemorrhage: 7.7% vs. 6.4%, respectively, for treatment vs. control

Interpretation:

Among patients with acute ischemic stroke receiving background intravenous thrombolytic therapy, intra-arterial treatment was beneficial at improving functional recovery. This treatment was safe with no notable difference in mortality or intra-cerebral hemorrhage. The treatment benefit was the same regardless of baseline systolic blood pressure. The benefit of achieving good functional recovery was maintained to 2 years. Intra-arterial treatment consisted mostly of retrievable stents, often with intra-arterial thrombolysis. The findings from this trial contrast with several other recently reported trials. Time to treatment was shorter among those who received nongeneral anesthesia versus general anesthesia. Post hoc analysis revealed possible good clinical outcome among those who underwent endovascular therapy and received nongeneral anesthesia.

References:

Mulder MJ, Ergezen S, Lingsma HF, et al. Baseline Blood Pressure Effect on the Benefit and Safety of Intra-Arterial Treatment in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). Stroke 2017;Apr 21:[Epub ahead of print].

van den Berg LA, Dijkgraaf MG, Berkhemer OA, et al. Two-year outcome after endovascular treatment for acute ischemic stroke. N Engl J Med 2017;376:1341-9.

Presented by Dr. Olvert A. Berkhemer at the International Stroke Conference (ISC), February 13, 2015, Nashville, TN.

Berkhemer OA, Fransen PS, Beumer D, et al., on behalf of the MR CLEAN Investigators. A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. N Engl J Med 2015;372:11-20.

van den Berg LA, Koelman DL, Berkhemer OA, et al., on behalf of the MR CLEAN pretrial study group. Type of Anesthesia and Differences in Clinical Outcome After Intra-Arterial Treatment for Ischemic Stroke. Stroke 2015;Apr 7:[Epub ahead of print].


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