Activase® is proven to reduce disability at 90 days in patients treated within 3 hours of symptom onset 6
The National Institute of Neurological Disorders and Stroke (NINDS) Trial was a large, randomized, placebo-controlled trial of intravenous Activase versus placebo in patients with acute ischemic stroke (AIS) treated within 3 hours of stroke symptom onset and was carried out in 2 parts. 6,14
- Part 1 (n=291) assessed changes in neurologic deficits 24 hours after the onset of strokea
- Part 2 (n=333)
assessed whether treatment with Activase resulted in sustained
clinical benefit at 3 monthsb
aComplete resolution of neurologic deficit or an
improvement from baseline NIHSS score of 4 or more were defined as
early improvement. 6
bScores of 95 or greater on the Barthel index, ≤1 on the
NIHSS and the modified Rankin Scale, and 1 on the Glasgow Outcome
Scale were considered to indicate a favorable outcome. 6
Trial Design
NINDS trial design

aAdditional study controls;
pretreatment prothrombin time >15 seconds; anticoagulant use or
heparin use within the 48 hours preceding the onset of stroke
(patients taking aspirin were NOT excluded); elevated activated
partial thromboplastin time. Study treatment was initiated prior to
the availability of coagulation study results in patients without
recent use of oral anticoagulants and/or heparin and was
discontinued if the pretreatment prothrombin time (PT) was greater
than 15 seconds or the activated partial thromboplastin time (aPTT)
was elevated.
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bPatients were randomized (1:1) to receive either 0.9
mg/kg Activase (maximum of 90 mg) or placebo. A cranial CT scan was
performed prior to treatment to rule out the presence of
intracranial hemorrhage. Blood pressure was actively controlled
(185/110 mm Hg or lower) for 24 hours.
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cActivase- and placebo-treated patient results for the 4
outcome scales were compared together (generalized estimating equations).
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Efficacy
Learn about Activase efficacy
Activase showed statistically significant improvement on all 4 stroke scales used in Part 2 of the NINDS Trial

- Part 1 of the trial demonstrated no significant difference between the Activase and placebo groups in the primary outcome measure (NIHSS) at 24 hours after treatment. 6
- Patients treated with Activase within 3 hours of symptom onset had reduced disability and were at least 33% more likely to achieve minimal or no disability at 90 days vs placebo-treated patients
- Global odds ratio for favorable outcome: 1.7 (95% CI, 1.15-2.56, P=0.02) 6,b
aRelative increase was calculated based on the numbers
shown in the above chart. Relative benefit increase is calculated as
relative percentage-1.
bThe primary hypothesis was
tested with a global statistic (the Wald test). This global test
statistic simultaneously tests for effect in all 4 outcome measures
specified in the primary hypothesis (the Barthel Index, NIHSS,
modified Rankin Scale, and the Glasgow Outcome Scale). A favorable
outcome is defined as recovery with minimal or no disability.
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Safety
Review incidences of symptomatic intracranial hemorrhage (sICH) and mortality in patients who were administered Activase
As illustrated, sICHa occurred more commonly in Activase-treated patients. In addition, 90-day mortality rates were not significantly different between the Activase and placebo groups.

- Of the 6.4% of Activase-treated patients who experienced an sICH within 36 hours, 45% (9/20) were fatal and 55% (11/20) were nonfatal. 14
- There was
no significant difference in 90-day mortality rates between
Activase- and placebo-treated patients. 6
Additional safety information from the NINDS trial
- Total intracranial hemorrhage rate (all time periods, both symptomatic and asymptomatic) was 15.4% for Activase- and 6.4% for placebo-treated patients (P<0.01) 6
- New ischemic stroke rate (within the first 3 months following study intervention) was 5.8% for Activase- and 5.4% for placebo-treated patients (P=1.00) 6
a Symptomatic intracranial hemorrhage within 36 hours was defined as the occurrence of sudden clinical worsening followed by subsequent verification of intracranial hemorrhage on CT scan. 6
DID YOU KNOW?
- The NINDS Trial showed that Activase given within 3 hours of
symptom onset of AIS reduced the incidence of disability among
treated patients compared with placebo at 3 months.
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