|Level of Evidence
Randomized, Open-label, Blinded end-point, Multi-center
||n = 500
with acute ischemic stroke and a proximal intracranial occlusion of the
anterior circulation confirmed on imaging (CTA, MRA, or DSA)
Age ≥ 18
of the distal intracranial carotid artery, middle cerebral artery (M1 or M2),
or anterior cerebral artery (A1 or A2), established by imaging
Treatment initiation within 6 hours of stroke
exclusion criteria for intra-arterial treatment (arterial blood pressure
exceeding 185/110 mmHg, blood glucose less than 2.7 or over
22.2 mmol/L (48 to 400 mg/dL), treatment with IV thrombolysis in a dose
exceeding 0.9 mg/kg or 90 mg, cerebral infarction in the distribution
of the relevant occluded artery in the previous 6 weeks)
Specific exclusion criteria for intra-arterial
thrombolysis (history of cerebral hemorrhage, severe head injury in < 4,
treatment with oral thrombin or factor X antagonists)
N = 267
(53.4%): Control Group = Usual care
N = 233
(46.6%): Intervention Group =
Intra-arterial treatment (delivery of thrombolytic, mechanical thrombectomy, or
both) plus usual care
Thrombolytic therapy included 1 of 2 options: 1)
maximum of 90 mg alteplase loading dose if no prior alteplase was given or
restricted to 30 mg if a prior dose was used. 2) max dose of 1,200,000 IU of
urokinase if no prior alteplase was given or 400,000 IU if alteplase was
Rankin score at 90 days
- Score ranges from 0 (no symptoms) to 6 (death)
with a score of less than or equal to 2 being functional independence.
parameter vessel recanalization at 24 hours (Clot Burden score and
size at 5 days assessed with ASPECTS
infarct volume calculation
NIHSS and NIH supplemental motor scale at
24 hours and at 1 week or discharge
were assigned to intra-arterial treatment group and 267 to usual care alone.
median age was mid 60s, 58% being males, and having a median NIH stroke scale
median time to groin puncture was 4 hours and 20 minutes.
patients (89.0%) were treated with IV tPA before randomization. There were too
few that were not treated with IV tPA prior to endovascular intervention to
draw any statistically significant conclusions.
stents were used in 190 of the 233 patients (81.5%).
with a modified Rankin score of 0-2 at 90 days in the intervention group was
32.6% vs. 19.1% in the usual care group - absolute difference of 13.5
percentage points (95% CI, 5.9 to 21.2). The adjusted common odds ratio (OR)
was 1.67 (95% CI, 1.21 to 2.30).
were no significant difference in mortality
Complication rate was 6% with no significant
differences in symptomatic intracerebral hemorrhage. However, the intervention group experienced
more new ischemic strokes involving a different vascular territory (5.6% vs
0.4%, p < 0.001).
||Number Needed to Treat = 7
||Intra-arterial therapy in conjunction with IV tPA is
safe and effective in patients presenting with an acute ischemic stroke
secondary to a large, proximal occlusion of the anterior circulation.
||16 medical centers in the Netherlands
||Dutch Heart Foundation and others
While MR CLEAN did conduct imaging
to identify a proximal occlusion in the anterior circulation, it did not
require evidence of an ischemic penumbra with an infarcted core for enrollment.
Urokinase is also not a treatment
option in the United States like alteplase (Activase).
Patients were not enrolled until
after the administration of IV tPA suggesting that non-responsive patients may
have been preferentially selected.
day modified Rankin Score was calculated by a telephone interview and
subjective report by the patient and/or representative.