In acute ischemic stroke...NINDS* pivotal trial shows
30% more patients had favorable outcomes with
Activase (t-PA) at 3 months†

3 months: more patients recover with minimal or no disability (1)
  • *
  • NINDS = National Institute of Neurological Disorders and Stroke.

NIH = National Institutes of Health.
Favorable outcome = Barthel, 95 or 100; modified Rankin, 0 or 1; Glasgow, 1; NIH Stroke Scale, <1.
P value is based on a global scale.

Part 2 of a randomized, double-blind, placebo-controlled study (N=333) conducted by NINDS of patients at 3 months after being treated for ischemic stroke with intravenous recombinant tissue plasminogen activator (n=168) or placebo (n=165) within 3 hours of onset.

  • †
  • A global test statistic was used to assess clinical outcome, according to the Barthel index, modified Rankin scale, Glasgow outcome scale, and NIH Stroke Scale. Part 1 of the study (n=291) tested results within 24 hours of stroke onset.
  • 11% to 13% absolute increase in favorable outcomes (Activase vs placebo)1
    • – There was an 11% absolute (55% relative) increase in the number of patients receiving Activase (t-PA) with an NIH Stroke Scale score of 0 or 1; a 12% absolute (32% relative) increase in the number of patients with minimal or no disability based on a score of 95 or 100 on the Barthel index; and 13% absolute increases in the numbers of patients with favorable outcomes based on the modified Rankin and Glasgow outcome scales, all vs placebo
  • The total dose for treatment of acute ischemic stroke should not exceed 0.9 mg/kg or 90 mg. Treatment is not recommended after 3 hours of acute ischemic stroke symptom onset or in patients with minor neurological deficit or with rapidly improving symptoms
1 year: neurologic benefits confirmed (2)

Adapted from Kwiatkowski TG, et al. N Engl J Med. 1999;340:1781-1787.

Note: NIH Stroke Scale scores were unavailable at 6 and 12 months because follow-up assessments were conducted by telephone.

Favorable outcome = Barthel, 95 or 100; modified Rankin, 0 or 1; Glasgow, 1.

A 1-year follow-up study of outcome data for the 624 patients enrolled in the original 2-part NINDS Study, using intent-to-treat analysis (26 patients missing at 12-month assessment considered to have unfavorable outcomes). There were 312 patients in each group, those treated for ischemic stroke with t-PA. A favorable outcome was defined as minimal or no disability as measured by the Barthel index, the modified Rankin scale, and the Glasgow outcome scale.

  • 11% to 13% absolute increase in neurologic recovery (Activase vs placebo)2
    • – There was a 12% absolute (32% relative) increase in the number of patients receiving Activase (t-PA) with minimal or no disability based on a score of 95 or 100 on the Barthel index; a 13% absolute (46% relative) increase in the number with minimal or no disability based on a score of 0 or 1 on the modified Rankin scale; and an 11% absolute (34% relative) increase in the number with minimal or no disability based on a score of 1 on the Glasgow outcome scale.
  • High-risk patients showed reduced, but still favorable, clinical outcome
    • – High risk includes patients presenting with severe neurologic deficit (NIH Stroke Scale score >22) or advanced age (>77 years)3
    • – ICH risk may be increased in these patients. Analyses for efficacy suggested a reduced but still favorable clinical outcome for Activase-treated patients with severe neurological deficit or advanced age at presentation
    • – Subsequent studies have found that Activase (t-PA) benefits patients with severe stroke symptoms, regardless of baseline NIH Stroke Scale scores4,5

Independent reviews support positive findings

  • Follow-up studies demonstrated that original NINDS trial outcomes were not biased by baseline imbalances (eg, NIH Stroke Scale score, severity, age), a previous misconception4,5
  • After consideration of baseline imbalances, favorable outcomes were more than twice as likely in patients treated with Activase (t-PA) in original trials at 3 months (OR 2.1; 95% CI, 1.5–2.9)4

Indication: Activase is indicated for the management of acute ischemic stroke in adults for improving neurological recovery and reducing the incidence of disability. Treatment should only be initiated within 3 hours after the onset of stroke symptoms, and after exclusion of intracranial hemorrhage by a cranial computerized tomography (CT) scan or other diagnostic imaging method sensitive for the presence of hemorrhage (see CONTRAINDICATIONS in the full prescribing information).

Safety Information: All thrombolytic agents increase the risk of bleeding, including intracranial bleeding, and should be used only in appropriate patients. Not all patients with acute ischemic stroke will be eligible for Activase therapy, including patients with evidence of recent or active bleeding; recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or previous stroke; uncontrolled high blood pressure; or impaired blood clotting.


Please see full prescribing information.


References:
1.
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581-1587.
2.
Kwiatkowski TG, Libman RB, Frankel M, et al. Effects of tissue plasminogen activator for acute ischemic stroke at one year. N Engl J Med. 1999;340:1781-1787.
3.
The NINDS Stroke t-PA Stroke Study Group. Generalized efficacy of t-PA for acute stroke: subgroup analysis of the NINDS t-PA stroke trial. Stroke. 1997;28:2119-2125.
4.
Ingall TJ, O'Fallon WM, Asplund K, et al. Findings from the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial. Stroke. 2004;35:2418-2424.
5.
Kwiatkowski TG, Libman R, Tilley BC, et al. The impact of imbalances in baseline stroke severity on outcome in the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator stroke study. Ann Emerg Med. 2005;45:377-384.
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