Table 1.
Randomised controlled trials of rt-PA in acute ischaemic stroke, design characteristics, and other key factors
|
Trial design |
Patients |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Number of patients | Method of randomisation | Dose | Control | Antithrombotic drug use | Age inclusion range | Stroke type | Exclusion criteria* for CT-defined ischaemia | Time after stroke | Final follow-up | Follow-up method (independent) | |
| Mori et al,13 1992 | 31 | Seq Pack | 0·6 mg/kg (34 mg) or 0·9 mg/kg (51 mg) | Placebo | Avoid for 24 h | 18–80 years | Carotid territory; ICA or MCA occlusion on angiography | Visible infarction | <6 h | 4 weeks | At clinic (not stated) |
| JTSG,14 1993 | 98 | Seq Pack | 0·6 mg/kg (34 mg) | Placebo | Avoid for 24 h | 18–80 years | Carotid territory; ICA or MCA occlusion on angiography | Visible infarction | <6 h | 4 weeks | At clinic (not stated) |
| Haley et al,15 1993 | 27 | Seq Pack | 0·85 mg/kg | Placebo | Avoid intravenous heparin for several hours | 18–80 years | Any ischaemic stroke | None | <3 h | 3 months | At clinic (not stated) |
| ECASS,2 1995 | 620 | Seq Pack | 1·1 mg/kg (maximum 100 mg) | Placebo | Aspirin or intravenous heparin not allowed; subcutaneous heparin allowed for <24 h; thereafter, any antithrombotic allowed | 18–80 years | Carotid territory | Visible infarction greater than a third of MCA territory | 6 h | 3 months | At clinic (not stated) |
| NINDS,1 1995 | 624 | Seq Pack | 0·9 mg/kg (maximum 90 mg) | Placebo | Avoid for 24 h | 18–80 years† | Any except very mild and very severe | None | 3 h | 3 months | At clinic (masked independent clinician) |
| ECASS II,3 1998 | 800 | Seq Pack | 0·9 mg/kg (maximum 90 mg) | Placebo | Aspirin or intravenous heparin not allowed; subcutaneous heparin allowed for <24 h | 18–80 years | Carotid territory | Visible infarction greater than a third of MCA territory | 6 h | 3 months | At clinic (not stated) |
| ATLANTIS A,16 2000 | 142 | Seq Pack | 0·9 mg/kg (maximum 90 mg) | Placebo | Avoid for 24 h | 18–80 years | As for NINDS | None | 6 h | 3 months | At clinic (masked independent clinician) |
| ATLANTIS B,17,18 1999 | 613 | Seq Pack | 0·9 mg/kg (maximum 90 mg) | Placebo | Avoid for 24 h | 18–80 years | As for NINDS | Visible infarction greater than a third of MCA territory | Most within 5 h | 3 months | At clinic (masked independent clinician) |
| ECASS 3,7 2008 | 821 | Central telephone or internet based | 0·9 mg/kg (maximum 90 mg) | Placebo | Avoid for 24 h | 18–80 years | As for NINDS | Visible infarction greater than a third of MCA territory | 3·0–4·5 h | 3 months | At clinic (masked independent clinician) |
| Wang et al,19 2003 | 100 | Seq Pack | 0·9 mg/kg (maximum 90 mg) | Open control | Avoid for 24 h | 18–80 years | As for NINDS | Any visible infarction | 6 h | 3 months | At clinic (not stated) |
| EPITHET,20 2008 | 101 | Seq Pack | 0·9 mg/kg (maximum 90 mg) | Placebo | Avoid for 24 h | 18–80 years† | As for NINDS | Visible infarction greater than a third of MCA territory | 3–6 h | 3 months | At clinic (not stated) |
| IST-3,21 2012 | 3035 | Central telephone or internet based | 0·9 mg/kg (maximum 90 mg) | Placebo first 276 patients, open control thereafter | Avoid for 24 h; start aspirin at 24 h unless contraindicated | ≥18 years | All subtypes | Visible infarct only if it appears >6 h after stroke—ie, incompatible with stated time after stroke | 6 h | 6 months | Centralised telephone or postal questionnaire (yes) |
rt-PA=recombinant tissue plasminogen activator. Seq Pack=randomised by taking the next of a sequentially numbered pack of active drug or placebo. ICA=internal carotid artery. MCA=middle cerebral artery.
*
Haemorrhage and mimics were excluded in all studies.
†
NINDS included 69 patients and EPITHET included 25 patients older than 80 years.