Table 1.
Phase III trials in acute ischemic stroke using mRS as primary outcome published between January 2007 and July 2014.
| Clinical trial (publ. year) | Intervention | Number of pts. | Primary outcome (favourable score) |
Method of analysis | Result of trial |
|---|---|---|---|---|---|
| CATIS (2014) | Antihypertensive | 4,071 | mRS at 14 d (0–2) | χ 2 test (unadjusted), OR by logistic regression | Neutral |
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| URICO-ICTUS (2014) | Uric acid | 421 | mRS at 90 d (0-1 (or 2 if premorbid score was 2)) | Log-binomial regression (adjusted) | Neutral |
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| ALIAS Part 2 (2013) | Albumin | 848 | mRS and NIHSS at 90 d (0-1) | GLM with log link (adjusted) | Neutral |
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| AXIS-2 (2013) | Filgrastim (G-CSF) | 328 | mRS at 90 d | Ordinary least squares | Neutral |
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| CERE-LYSE-1 (2013)∗ | Cerebrolysin + alteplase | 119 | mRS at 90 d | Ordinal logistic regression | Neutral, trial terminated |
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| CHIMES (Neuroaid) (2013)∗ | MLC601 | 1,100 | mRS at 3 mo | Ordinal logistic regression (adjusted) | Neutral |
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| ECCS-AIS (2013) | Edaravone or citicoline | 71 | mRS and NIHSS at 3 mo | ANOVA (mean mRS score) | Positive for Edaravone |
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| IMS III (2013)∗ | Endovascular therapy | 656 | mRS at 3 mo (0–2) | CMH test (adjusted) | Neutral, trial stopped early |
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| Integrated rehab (2013) | Integrated rehabilitation | 69 | mRS at 90 d (0-1) | Dichotomous (unavailable) | Neutral |
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| MAC SI (2013)∗ | DP-b99 | 446 | mRS at 90 d | CMH test with modified ridit scores | Neutral (p = 0.105) |
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| NBP (2013) | dl-3-n-Butylphthalide | 573 | mRS and BI at 90 d (0-1) | χ 2 test | Positive (p = 0.002) |
|
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| NEST 1 & 2 pooled (2013) | Transcranial laser therapy | 780 | mRS at 90 d (0–2) | Logistic regression (adjusted) | Positive |
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| SYNTHESIS Expansion (2013) | Endovascular therapy | 362 | mRS at 3 mo (0-1) | Fisher's exact test, OR by M-H test | Neutral |
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| CASTA (2012) | Cerebrolysin | 1,070 | Global test: mRS, NIHSS, and BI at 90 d | Global directional test (Wilcoxon-Mann-Whitney test) | Neutral |
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| Early aspirin (2012) | Aspirin + alteplase | 642 | mRS at 3 mo (0–2) | Dichotomous (unspecified) | Neutral, terminated early, increased risk of SICH |
|
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| Ginsenoside-Rd (2012)∗ | Ginsenoside-rd | 390 | mRS, NIHSS, BI at 90 d (0–2) | CMH test (adjusted), OR by logistic regression | Positive |
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| Home rehabilitation (2012) | Home rehabilitation | 60 | mRS, BI, and EQ-5D at 2 yrs (0-1) | Dichotomous (unspecified) | Positive |
|
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| ICTUS (2012) | Citicoline | 2,298 | global test: mRS, NIHSS, BI at 90 d | Logistic regression (adjusted) | Neutral |
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| IST-3 (2012) | rt-PA | 3,035 | OHS at 6 mo (0–2) | Logistic regression (adjusted) | Neutral |
|
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| Minocycline (2012) | Minocycline | 50 | mRS, NIHSS, BI at 90 d | t-test and Mann-Whitney U test | Positive |
|
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| Scalp electrical acupuncture (2012) | Scalp electrical acupuncture | 62 | NIHSS, mRS, BI at postacupuncture | Fisher's exact test | Neutral |
|
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| ALIAS Part 1 (2011) | Albumin | 316 | Composite mRS and NIHSS at 90 d (0-1) | Dichotomous (unspecified) | Neutral |
|
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| Aphasia (2011) | Piracetam | 49 | mRS, GAT, NIHSS, and BI scores at 24 wks | t-test and Mann-Whitney U test | Neutral |
|
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| CAIST (2011) | Cilostazol | 458 | mRS at 90 d (0–2) | Normal approximation to binomial | Comparable to aspirin (efficacy and safety) |
|
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| QASC (2011) | Symptom management initiative | 1,696 | mRS, BI, SF-36, PSC score at 90 d (0-1) | Logistic regression with GEE | Positive |
|
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| SCAST (2011)∗ | Candesartan | 2,029 | mRS at 6 mo | Ordinal logistic regression | Negative |
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| SENTIS (2011) | NeuroFlo device | 515 | Global endpoint: mRS, NIHSS, BI, and GOS at 90 d (0-1) | Logistic regression (adjusted) | Neutral |
|
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| t-PA in elderly (2011) | t-PA | 97 | mRS at discharge (0–2) | Dichotomous (unavailable) | Neutral |
|
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| COSSACS (2010) | Antihypertensive | 763 | mRS at 2 wks (0–2) | χ 2 test (OR by adjusted logistic regression) | Neutral, trial stopped early |
|
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| EARLY (2010)∗ | Aspirin + dipyridamole <24 h | 548 | mRS at 90 d (0-1) | CMH test (adjusted), OR by logistic regression | Neutral |
|
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| ASP I & II interim (2009) | Ancrod | 508 | mRS at 90 d (dependent on prestroke score) | Logistic regression (adjusted) | Neutral |
|
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| CHHIPS (2009) | BP manipulation | 180 | mRS at 2 wks (0–3) | Logistic regression | Neutral, study underpowered |
|
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| DIAS-2 (2009) | 90 & 125 µg/kg desmoteplase | 193 | Composite mRS, NIHSS, and BI at 90 d | Global statistical test | Neutral |
|
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| EDO (2009) | Edaravone | 401 | mRS at 3 mo (0-1) | Dichotomous (unavailable) | Neutral |
|
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| NEST-2 (2009) | Transcranial laser therapy | 660 | mRS and NIHSS at 90 d (0–2) | Logistic regression (adjusted) | Neutral (p = 0.094) |
|
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| PAIS (2009) | Paracetamol | 1,400 | mRS at 3 mo | Sliding dichotomy | Neutral |
|
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| AbESTT-II (2008) | Abciximab | 801 | mRS at 3 mo | Sliding dichotomy (mRS is 0 if NIHSS is 4–7, 0-1 if 8–14, and 0–2 if 15–22) | Neutral |
|
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| ECASS III (2008) | Alteplase (rt-PA) | 821 | mRS at 90 d (0-1) | χ 2 test (OR and RR) | Positive |
|
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| Ultrasound guided TCCS (2008) | Transcranial color-coded sonography | 37 | mRS, BI, and death at 90 d | Mann-Whitney U test | Neutral mRS, overall benefit of TCCS therapy |
|
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| MELT (2007) | Urokinase | 114 | mRS at 90 d (0–2) | Fisher's exact test | Neutral, trial stopped early |
|
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| SAINT II (2007)∗ | NXY-059 | 3,306 | mRS at 90 d | CMH test (adjusted) | Neutral |
|
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| Statin withdrawal (2007) | Statin withdrawal | 89 | mRS at 3 mo (0–2) | Logistic regression | Negative |
∗Ordinal analyses. CMH: Cochran-Mantel-Haenszel, GEE: general estimating equation, GLM: generalised linear model, OR: odds ratio, and RR: relative risk.