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

3 months: more patients recover with minimal or no disability(1)

  • *
  • NINDS=National Institute of Neurological Disorders and Stroke.

Favorable outcome=Barthel, 95 or 100; Modified Rankin, 0 or 1; Glasgow, 1; NIHSS, <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 NIHSS. Part 1 of the study (n=291) tested results within 24 hours of stroke onset.


  • 11% to 13% absolute increase in favorable outcomes for Activase (t-PA) at 3 months vs placebo1
    • – There was an 11% absolute (55% relative) increase in the number of patients receiving Activase (t-PA) with an NIHSS 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
  • Treatment is not recommended after 3 hours of acute ischemic stroke symptom onset or in patients with minor neurologic 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.

Note: NIHSS 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 for Activase (t-PA) at 1 year vs placebo2
    • – 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 (NIHSS 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 (t-PA)–treated patients with severe neurologic deficit or advanced age at presentation
    • – Subsequent studies have found that Activase (t-PA) benefits patients with severe stroke symptoms, regardless of baseline NIHSS scores4,5

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Independent reviews support positive findings

Indication
Activase (Alteplase) 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).

Safety Information
Activase therapy in patients with AIS is contraindicated in certain situations (eg, suspicion of subarachnoid hemorrhage on pretreatment evaluation, recent (within 3 months) intracranial or intraspinal surgery, history of intracranial hemorrhage, uncontrolled hypertension at time of treatment, active internal bleeding, known bleeding diathesis (eg, current use of oral anticoagulants, administration of heparin within 48 hours of onset of stroke, platelet count <100,000) (see CONTRAINDICATIONS for full list).

The most common complication during Activase therapy is bleeding. Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, pericardial) occur, Activase therapy should be discontinued immediately. Death and permanent disability are not uncommonly reported in patients who have experienced stroke (including intracranial bleeding) and other serious bleeding episodes.

The risks of Activase therapy may be increased and should be weighed against the anticipated benefits in certain conditions. [See WARNINGS in full prescribing information].

  • Patients with severe neurological deficit (eg, NIHSS >22) at presentation. There is an increased risk of intracranial hemorrhage in these patients.
  • Patients with major early infarct signs on a computerized cranial tomography (CT) scan (eg, substantial edema, mass effect, or midline shift).

Treatment of patients with minor neurological deficit or with rapidly improving symptoms is not recommended.

Orolingual angioedema has been observed in postmarketing experience in patients treated with Activase for AIS. Patients should be monitored during and for several hours after infusion for signs of orolingual angioedema.

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References:
1.
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.
NINDS 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.