Table 1.
Positive trials summary
| Study, country, publication year | n | Endpointsa | Effect measureb | Primary sponsor | Termination | Inclusion criteria | Intervention | Control |
|---|---|---|---|---|---|---|---|---|
|
NINDS [24] USA, 1995 |
624 | Global testc,d | 1.7 (1.2–2.6) | Public | Per protocol | Selective (time) | IVT | Placebo |
|
CAST [13] China, 1997 |
21,106 |
28-day death Death or dependence at discharge |
p = 0.04e p = 0.08e |
Public | Per protocol | Broad | Aspirin | Placebo |
|
PROACT-2 [31] USA, 1999 |
180 | mRS 0–2 | p = 0.04f | Commercial | Per protocol | Selective (time, LVO) | IA prourokinase + heparin | Heparin |
|
SAINT-1 [5] Global, 2006 |
1722 | mRS shift | 1.20g (1.01–1.42) | Commercial | Per protocol | Selective (time), Broad (clinical) | Neuroprotection (NXY-059) | Placebo |
|
ECASS-3 [19] European, 2008 |
821 | mRS 0–1 | 1.42 (1.02–1.98) | Commercial | Per protocol | Selective (time) | IVT | Placebo |
|
DESTINY-2 [49] Germany, 2014 |
112 | mRS 0–4 at 6 months | 2.91 (1.06–7.49) | Public | Per protocol | Selective (rare subgroup, imaging) | Hemicraniectomy | Conservative treatment |
|
MR-CLEAN [40] Netherlands, 2015 |
500 | mRS shift | 1.67 (1.21–2.30) | Public | Per protocol | Selective (time, LVO) | MT + Standard care (90.6% IVT) | Standard care (87.1% IVT) |
|
SWIFT-PRIME [45] Global, 2015 |
196 |
mRS shift mRS 0–2 (secondary) |
p < 0.001h RR 1.70 (1.23–2.33) |
Commercial | Premature | Selective (time, LVO) | MT + IVT | IVT alone |
|
ESCAPE [43] Canada, 2015 |
316 | mRS shift | 3.1 (2.0–4.7) | Commercial | Premature | Selective (time, LVO) | MT + Standard care (72.7% IVT) | Standard care (78.7% IVT) |
|
EXTEND-IA [42] Australia, 2015 |
70 |
Reperfusioni Early improvementj |
4.7 (2.5–9.0) 6.0 (2.0–18.0) |
Public | Premature | Selective (time, LVO, imaging) | MT + IVT | IVT alone |
|
REVASCAT [44] Spain, 2015 |
206 | mRS shift | 1.7 (1.05–2.8) | Public | Premature | Selective (time, LVO) | MT + Standard care (68.0% IVT) | Standard care (77.7% IVT) |
|
THRACE [41] France, 2016 |
414 | mRS 0–2 | 1.55 (1.05–2.30) | Public | Premature | Selective (time, LVO) | MT + IVT | IVT alone |
|
DEFUSE-3 [47] USA, 2018 |
182 | mRS shift | Unadjusted OR 2.77 (1.63–4.70) | Public | Premature | Selective (time, LVO, imaging) | MT + Standard care | Standard care |
|
DAWN [48] USA, 2018 |
206 |
Utility-weighted mRS % of mRS 0–2 |
ADk 2.0 (1.1–3.0) ADk 33 (21–44) |
Commercial | Premature | Selective (time, LVO, imaging) | MT + Standard care (5.0% IVT) | Standard care (13.0% IVT) |
|
WAKE-UP [28] European, 2018 |
503 | mRS 0–1 | 1.61 (1.09–2.36) | Public | Premature | Selective (imaging) | IVT | Placebo |
|
EXTEND [29] Australia, 2019 |
225 | mRS 0–1 | 1.44 (1.01–2.06) | Public | Premature | Selective (time, imaging) | IVT | Placebo |
|
RESILIENT [46] Brazil, 2020 |
221 | mRS shift | 2.28 (1.41–3.69) | Public | Premature | Selective (time, LVO) | MT + Standard care (68.5% IVT) | Standard care (71.8% IVT) |
AD: adjusted difference; IA: intra-arterial; IVT: intravenous thrombolysis (alteplase); LVO: large vessel occlusion; mRS: modified Rankin Scale; MT: mechanical thrombectomy; OR: odds ratio; RR: risk ratio
aPrimary or co-primary endpoints (at 90 days)
bValues presented are adjusted odds ratios with 95% confidence intervals
cPart 1 was negative, part 2 and combined results were positive
dGlobal test statistic for four primary outcome measures
eTwo-sided p-value
f15% absolute increase in favorable outcome with intra-arterial prourokinase
gEffect was not reproduced in SAINT-2 (n = 3306, OR 0.94, 95% CI 0.83–1.06)
hCochran-Mantel–Haenszel test
iDefined as the percentage reduction in the perfusion-lesion volume between initial imaging and 24-h imaging
jDefined as a reduction of 8 points or more on the National Institutes of Health Stroke Scale or a score of 0 or 1 at 3 days
kBayesian trial design. For every co-primary outcome, adjusted differences and 95% credible intervals are presented