1. Ischemic stroke onset within 3 hours of drug administration.
2. Measurable deficit on NIH Stroke Scale examination.
3. Patient's computed tomography (CT) does not show hemorrhage or nonstroke cause of deficit.
4. Patient's age is >18 years.

1. Patient's symptoms are minor or rapidly improving.
2. Patient had seizure at onset of stroke.
3. Patient has had another stroke or serious head trauma within the past 3 months.
4. Patient had major surgery within the last 14 days.
5. Patient has known history of intracranial hemorrhage.
6. Patient has sustained systolic blood pressure >185 mmHg.
7. Patient has sustained diastolic blood pressure >110 mmHg.
8. Aggressive treatment is necessary to lower the patient's blood pressure.
9. Patient has symptoms suggestive of subarachnoid hemorrhage.
10. Patient has had gastrointestinal or urinary tract hemorrhage within the last 21 days.
11. Patient has had arterial puncture at noncompressible site within the last 7 days.
12. Patient has received heparin with the last 48 hours and has elevated PTT.
13. Patient's prothrombin time (PT) is >15 seconds.
14. Patient's platelet count is <100,000 uL.
15. Patient's serum glucose is <50 mg/dL or >400 mg/dL.

1. Patient has a large stroke with NIH Stroke Scale score >22.
2. Patient's CT shows evidence of large middle cerebral artery (MCA) territory infarction (sulcal effacement or blurring of gray-white junction in greater than 1/3 of MCA territory).

Randomized, prospective, multicenter, double blinded, placebo controlled.

Treatment within 6 hours using 1.1 mg/kg.

620 patients; outcome measures of Barthal index and modified Rankin at 90 days.

No difference in mortality and improved outcome in tPA group but incidence of hemorrhage higher.

109 patients included despite major protocol violations.

Most patients were enrolled after 3 hours (average time to treatment was 4.3 hours).

Randomized, prospective multicenter double blinded.

Four arms: strepto, ASA, both, neither.

Treatment within 6 hours.

Two parts: Part I double blinded, randomized placebo controlled with a 24-hour assessment using the NIHSS.

Part II 3-month assessment using the BI, RS, NIHSS, GCS.

Treatment within 3 hours using .9 mg/kg.

Part 1: 291patients - no difference in 24-hour outcome between tPA and placebo.

Part II: 333 patients - tPA provided a 32%Relative (12% absolute) better likelihood to have minimal or no disability at 90 days; odds ratio for improvement was 2 (95% CI 1.3 to 3.1).

Increased (6.4% vs. .6%) likelihood of symptomatic intracranial hemorrhage.

Patients treated with tPA were 30% more likely to have a favorable outcome at one year with no difference in mortality.

Rate of stroke recurrence was the same in both groups; type of stroke had no difference in outcome.

For every 100 patients treated with acute stroke, 11 additional patients would have a favorable outcome.

Randomized, double-blinded, multi-center using modified Rankin at 90 days.

Stratified 0-3 and 3-6 hour groups.

Only 4.6 % of patients had significant changes in more than one third of the MCA.

No benefit to treatment found though there was a trend toward improved outcome in the few patients treated within 3 hours.

9% symptomatic hemorrhage vs. 3% in controls.

Patients were routinely started on heparin.

Osmodiuretics were used.

No control.

Placebo-controlled, double-blinded, randomized, multicenter.

Treatment 0-3, 3-5, >5 hours from stroke onset with 90 day follow-up.

No difference between placebo and tPA in patients treated after 3 hours of stroke onset.

tPA associated with a 7% symptomatic hemorrhage rate vs. 1.1% with placebo.

Mortality was 7% vs. 11%.

tPA offers no benefit when administered more than 3 hours after onset of acute stroke.

Retrospective, observational review.

4 hospitals; all tPA administered by emergency physicians.

37 patients; symptomatic intracranial hemorrhage in 10.8% (4).

Only 9 patients had neurology consult in the ED; 14 patients had no neurology consultation.

57% had normal or improved outcome at time of discharge from the hospital. Average hospital stay was 8 days.

Small number; no 3 or 6-month follow-up.

7 patients had protocol violations; all were tPA beyond the 3-hour window.

5 patients (9%) were treated outside of 3 hours.

Outcome measure was at 6 days vs. 3 months in most other studies.

Prospective, multicenter, consecutive patients (24 academic, 33 community hospitals).

Outcome assessed at 30 days.

389 patients; median time-to-treatment 2 hours, 44 minutes.

30-day mortality 13%; 43% functional, independent.

3.3% symptomatic intracranial hemorrhage.

43 patients; 42% had modified Rankin of 0-1.

7% symptomatic intracranial hemorrhage.

Protocol deviations were higher when emergency physician administered tPA vs. neurologist: 30 vs. 5%.

Education program decreased protocol deviations from 7 to 1.

Fibrinolytics increase symptomatic intracranial hemorrhage but risks are offset by decreased disability in survivors."

The data is promising and may justify the use of (tPA) in experienced centres in selected patients."

tPA must be limited to carefully selected patients within established protocols.

tPA should only be administered using NINDS criteria by physicians with expertise in stroke.

CTs should only be interpreted by those with expertise in neuroradiology.

tPA should be limited to centers with appropriate neurological and neuroimaging resources 24/7.