Key PointsQuestion
In patients with acute large vessel occlusion stroke, is
mechanical thrombectomy alone noninferior to combined intravenous
thrombolysis using 0.6-mg/kg alteplase plus mechanical thrombectomy
regarding functional outcomes?
Findings
In this randomized clinical trial of 204 patients, a favorable
functional outcome occurred in 59.4% of those randomized to mechanical
thrombectomy alone and in 57.3% of those randomized to combined
intravenous thrombolysis plus mechanical thrombectomy (odds ratio, 1.09
[95% confidence limit below the noninferiority margin of 0.74]).
Meaning
The findings failed to demonstrate noninferiority of
mechanical thrombectomy alone, compared with combined intravenous
thrombolysis plus mechanical thrombectomy, for favorable functional
outcome following acute large vessel occlusive ischemic stroke, although
the wide confidence intervals around the effect estimate also did not
allow a conclusion of inferiority.
Importance
Whether intravenous thrombolysis is needed in combination with
mechanical thrombectomy in patients with acute large vessel occlusion
stroke is unclear.
Objective
To examine whether mechanical thrombectomy alone is
noninferior to combined intravenous thrombolysis plus mechanical
thrombectomy for favorable poststroke outcome.
Design, Setting, and Participants
Investigator-initiated, multicenter, randomized, open-label,
noninferiority clinical trial in 204 patients with acute ischemic stroke
due to large vessel occlusion enrolled at 23 hospital networks in Japan
from January 1, 2017, to July 31, 2019, with final follow-up on October
31, 2019.
Interventions
Patients were randomly assigned to mechanical thrombectomy
alone (n = 101) or combined intravenous thrombolysis (alteplase at a
0.6-mg/kg dose) plus mechanical thrombectomy (n = 103).
Main Outcomes and Measures
The primary efficacy end point was a favorable outcome defined
as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death])
of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74,
assessed using a 1-sided significance threshold of .025 (97.5% CI).
There were 7 prespecified secondary efficacy end points, including
mortality by day 90. There were 4 prespecified safety end points,
including any intracerebral hemorrhage and symptomatic intracerebral
hemorrhage within 36 hours.
Results
Among 204 patients (median age, 74 years; 62.7% men; median
National Institutes of Health Stroke Scale score, 18), all patients
completed the trial. Favorable outcome occurred in 60 patients (59.4%)
in the mechanical thrombectomy alone group and 59 patients (57.3%) in
the combined intravenous thrombolysis plus mechanical thrombectomy
group, with no significant between-group difference (difference, 2.1%
[1-sided 97.5% CI, −11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI,
0.63 to ∞]; P = .18 for noninferiority). Among the 7 secondary
efficacy end points and 4 safety end points, 10 were not significantly
different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%];
difference, –0.8% [95% CI, –9.5% to 7.8%]; odds ratio, 0.90 [95% CI,
0.33 to 2.43]; P > .99). Any intracerebral hemorrhage was
observed less frequently in the mechanical thrombectomy alone group than
in the combined group (34 [33.7%] vs 52 [50.5%]; difference, –16.8%
[95% CI, –32.1% to –1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88]; P = .02).
Symptomatic intracerebral hemorrhage was not significantly different
between groups (6 [5.9%] vs 8 [7.7%]; difference, –1.8% [95% CI, –9.7%
to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24]; P = .78).
Conclusions and Relevance
Among patients with acute large vessel occlusion stroke,
mechanical thrombectomy alone, compared with combined intravenous
thrombolysis plus mechanical thrombectomy, failed to demonstrate
noninferiority regarding favorable functional outcome. However, the wide
confidence intervals around the effect estimate also did not allow a
conclusion of inferiority.
Trial Registration
umin.ac.jp/ctr Identifier: UMIN000021488
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