| Level of Evidence |
1b |
| Study Design |
Prospective,
Randomized, Open-label, Blinded end-point, Multi-center |
| Sample Size |
n = 500 |
| Population |
Patients
with acute ischemic stroke and a proximal intracranial occlusion of the
anterior circulation confirmed on imaging (CTA, MRA, or DSA) |
| Inclusion Criteria |
-
Age ≥ 18
years
-
NIHSS ≥6
-
Occlusion
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
onset |
| Exclusion Criteria |
-
General
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)
-
Coagulation
abnormalities
-
Specific exclusion criteria for intra-arterial
thrombolysis (history of cerebral hemorrhage, severe head injury in < 4,
treatment with oral thrombin or factor X antagonists) |
| Interventions |
-
N = 267
(53.4%): Control Group = Usual care
alone vs.
-
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
already given. |
| Follow Up |
90 days |
| Primary Endpoint |
- Modified
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.
|
| Secondary Endpoint |
-
Imaging
parameter vessel recanalization at 24 hours (Clot Burden score and
collateral score)
-
Infarct
size at 5 days assessed with ASPECTS
-
Final
infarct volume calculation
-
NIHSS and NIH supplemental motor scale at
24 hours and at 1 week or discharge |
| Results |
-
233
were assigned to intra-arterial treatment group and 267 to usual care alone.
-
The
median age was mid 60s, 58% being males, and having a median NIH stroke scale
of 17.
-
The
median time to groin puncture was 4 hours and 20 minutes.
-
445
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.
-
Retrievable
stents were used in 190 of the 233 patients (81.5%).
-
Patients
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).
-
There
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). |
| NNT/NNH |
Number Needed to Treat = 7 |
| Conclusions |
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. |
| Location |
16 medical centers in the Netherlands |
| Funding |
Dutch Heart Foundation and others |
| Comments |
-
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.
-
90
day modified Rankin Score was calculated by a telephone interview and
subjective report by the patient and/or representative. |
