Patients were randomized to receive either 0.9 mg/kg Activase (maximum of 90 mg), or placebo. Activase was administered as a 10% initial bolus over 1 minute followed by continuous intravenous infusion of the remainder over 60 minutes (See DOSAGE AND ADMINISTRATION). In patients without recent use of oral anticoagulants or heparin, study treatment was initiated prior to the availability of coagulation study results. However, the infusion was discontinued if either a pretreatment prothrombin time (PT) > 15 seconds or an elevated activated partial thromboplastin time (aPTT) was identified. Although patients with or without prior aspirin use were enrolled, administration of anticoagulants and antiplatelet agents was prohibited for the first 24 hours following symptom onset.

The initial study (NINDS-Part 1, n=291) evaluated neurological improvement at 24 hours after stroke onset. The primary endpoint, the proportion of patients with a 4 or more point improvement in the National Institutes of Health Stroke Scale (NIHSS) score or complete recovery (NIHSS score = 0), was not significantly different between treatment groups. A secondary analysis suggested improved 3-month outcome associated with Activase treatment using the following stroke assessment scales: Barthel Index, Modified Rankin Scale, Glasgow Outcome Scale, and the NIHSS.

A second study (NINDS-Part 2, n=333) assessed clinical outcome at 3 months as the primary outcome. A favorable outcome was defined as minimal or no disability using the four stroke assessment scales: Barthel Index (score ≥ 95), Modified Rankin Scale (score ≤ 1), Glasgow Outcome Scale (score = 1), and NIHSS (score ≤ 1). The results comparing Activase- and placebo-treated patients for the four outcome scales together (Generalized Estimating Equations) and individually are presented in Table 3. In this study, depending upon the scale, the favorable outcome of minimal or no disability occurred in at least 11 per 100 more patients treated with Activase than those receiving placebo. Secondary analyses demonstrated consistent functional and neurological improvement within all four stroke scales as indicated by median scores. These results were highly consistent with the 3-month outcome treatment effects observed in the Part 1 study.

Table 3
The NINDS t-PA Stroke Trial, Part 2
3-Month Efficacy Outcomes

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