TABLE 1.
Characteristics of the Included RCTsa
| Reference, year |
Intervention (maximum dosage) |
No. of patients (male %) |
Age (y), mean ± SD or median (range) |
Primary outcome |
NIHSS score, mean/ median |
NIHSS score ≥20 |
Occlusion | Time from symptom onset to treatment (min), median/mean ± SD |
Recanalization (TICI) |
Quality of studiesb |
|---|---|---|---|---|---|---|---|---|---|---|
| Ciccone et al,7 2013 |
I = IA tPA (0.9 mg/kg)c + IV heparin ± MT |
181 (59) | 66±11 | mRS score ≤ 1 at 90 d | 13 | NA | Anterior and posterior circulation— complete data NA |
Median = 225 | NA | + |
| C = IV tPA (0.9 mg/kg) | 181 (57) | 67±11 | 13 | NA | Median = 165 | NA | ||||
| Broderick et al,6 2013 |
I = IVd + IA tPA (22 mg) + IV heparin ± MT |
434 (50) | 69 (23–89) | mRS score ≤2 at 90 d | 17 | 132 | M1 = 135, ICA = 65, single M2 = 61, multiple M2 = 22, basilar occlusion = 4 |
Mean time to IV tPA = 122±38, mean time to groin puncture = 208±47, mean time to IA therapy = 249±51 Mean =121 ±34 |
Grade 2b–3; ICA (38%), M1 (41%), single M2 (44%), multiple M2 (23%) |
+ |
| C = IV tPA (0.9 mg/kg) |
222 (55) | 68 (23–84) | 16 | 72 | NA |
|
NA | |||
| Kidwell et al,8 2013, penumbrae |
I = MT ± IA/IV tPAf(14 mg) |
34 (50) | 66±13 | Improvement in mRS score level |
16 | NA | ICA = 6, M1 = 18, M2 = 10 |
Mean time to groin puncture = 381 ±74 |
Grade 2a–3 at day 7 = 67% |
+ |
| C = standard medical care ± IV tPA |
34 (44) | 66±17 | 16 | NA | ICA = 5, M1 = 23, M2 = 6 |
NA | Grade 2a–3 at day 7 = 93% |
|||
| Kidwell et al,8 2013, nonpenumbra |
I = MT ± IA/IV tPA (14 mg) |
30 (43) | 62±12 | 19 | NA | ICA = 7, M1 = 21, M2 = 2 |
Mean time to groin puncture = 381 ±74 |
Grade 2a–3 at day 7 = 77% |
+ | |
| C = standard medical care ± IV tPA |
20 (60) | 69±16 | 21 | NA | ICA = 2, M1 = 16, M2 = 2 |
NA | Grade 2a–3 at day 7 = 78% |
|||
| Ciccone et al,21 2010 |
I = IA tPA (0.9 mg/kg)g + IV heparin ± MT |
29 (76) | 61 ±14 | mRS score ≤1 at 90 d | 17 | NA | Anterior and posterior circulation— complete data NA |
Median time to start of treatment = 195 |
NA | − |
| C = IV tPA (0.9 mg/kg) |
25 (75) | 64±12 | 16 | NA | Median time to start of treatment = 195 |
NA | ||||
| Sen et al,22 2009 |
I = IA tPA (22mg) | 3 | 68±16 |
|
16 | NA | M1 = 5, M2 = 1, terminal ICA = 1 |
Mean time to thrombolysis = 236 |
Grade 2a–3 = 3 | + |
| C = IV tPA (0.9 mg/kg ) |
4 | NA | Mean time to thrombolysis = 170 |
Grade 2a–3 = 0 | ||||||
AIS = acute ischemic stroke; C = control; I = intervention; IA = intra-arterial; ICA = internal carotid artery; IQR = interquartile range; IV = intravenous; LVO = large vessel occlusion; MCA = middle cerebral artery; MI = first segment of MCA (horizontal); M2 = second segment of MCA (insular); mRS = modified Rankin Scale; MT = mechanical thrombolysis; NA = not available; NIHSS = National Institutes of Health Stroke Scale; RCT = randomized controlled trial; sICH = symptomatic intracranial hemorrhage; TICI = thrombolysis in cerebral infarction; tPA = tissue plasminogen activator.
Represents quality of studies measured by the Jadad score; + = high quality; − = low quality.
Median tPA dose used = 40 mg (IQR, 20–50 mg).
From March 2006 to June 2011, two thirds of the total approved tPA dose was administered intravenously in the intervention arm (all patients were randomized within 40 min of starting IV tPA); after June 2011, the full dose of IV tPA was used even in the intervention arm. The mean dose of tPA received in the intervention arm = 60.3 ± 14.2 mg (IV tPA = 52.1 ± 12 and IA tPA = 13.3±6.7) and in the control arm = 72.5 ± 14.3 mg.
Penumbra was defined as predicted infarct core of ≤90 mL and a proportion of predicted infarct tissue within the at-risk region of ≤70%.
Mean IA tPA dose = 5.1 mg; overall, 44 (37%) patients received IV tPA.
Median IA tPA dose = 50 mg (IQR, 45–70 mg); median IV tPA dose in the control arm = 66.5 mg (IQR, 58–72 mg).