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The NINDS Trial - 1 Year Follow Up on Neurologic Outcomes

Summary:

  • The NINDS Trial:  1 - Year Follow Up
  • The original NINDS trial published in 1995 was a landmark trial demonstrated improvement in neurologic outcomes at 90 days with a NNT of a favorable outcome to be 7.  This lead to the FDA approval of alteplase in 1996 and EMEA approval in 2002 for acute ischemic stroke.
  • A 1 year follow up of this trial continued to show improvements in neurologic outcome, but not on mortality or chance for recurrent stroke.

NINDS Trial 1-Year Follow-Up Summary

  • Kwiatkowski TG et al. Effects of tissue plasminogen activator for acute ischemic stroke at one year. National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study Group. N Engl J Med 1999;340(23):1781-7. PubMed
    Level of Evidence 1a
    Study Design Prospective, Multicenter, Randomized, Double-Blind Trial in the United States (1991-1994) - originally published in 1995
    Sample Size N = 624 (total)
    Inclusion Criteria
    • Presenting within 3 hrs of onset of stroke symptoms
    • A deficit measurable on the NIH Stroke Scale (NIHSS)
    • Baseline CT brain showing no hemorrhage
    Exclusion Criteria
    • Stroke or serious head trauma within 3 months
    • Major surgery
    • History of intracerebral hemorrhage
    • SBP > 185 mm Hg or DBP > 100
    • Rapidly improving symptoms
    • GI or urinary hemorrhage in the past 21 days
    • Seizure at the onset of stroke
    • Taking anticoagulants
    • Platelets < 100,000
    • Glucose < 50 or > 400 mg/dL
    Interventions
    • r-tPA
    • Placebo
    Follow Up 6 & 12 months (the original trial went up to 3 months)
    Primary Endpoint To determine if IV tPA has improved clinical outcome if administered within 3 hours of onset of stroke symptoms at 1 year.
    Secondary Endpoint

    The trial was broken into 2 parts (using the Barthel Index, modified Rankin scale, Glasgow outcome, and NIHSS).

    • To determine if there was an early (< 24 hrs)
    • To determine if there was a late effect (3 months)
    Results
    • Using an intention-to-treat analysis for the combined results of the two parts of the trial at 6 months and 12 months, we found that the global statistic favored the t-PA group (OR for a favorable outcome at 6 months, 1.7; 95% CI, 1.3 to 2.3; OR at 12 months, 95% CI, 1.7; 1.2 to 2.3).
    • The patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at 12 months than were the placebo-treated patients (absolute increase in the proportion with a favorable outcome, 11 to 13 percentage points).
    • There was no significant difference in mortality at 12 months (24 percent vs. 28 percent, P=0.29).
    • There was no interaction between the type of stroke identified at base line and treatment with respect to the long-term response.
    • The rate of recurrent stroke at 12 months was similar in the two groups.
    Conclusions During 12 months of follow-up, the patients with acute ischemic stroke who were treated with t-PA within three hours after the onset of symptoms were more likely to have minimal or no disability, than the patients given placebo.
    Location 8 medical centers around the United States between 1991-1994
    Funding National Institutes of Health (NIH)
    Comments The original NINDS trial published in 1995 is considered landmark because it was the basis for alteplase's approval back in 1996 by the FDA and in 2002 by EMEA.

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MESH Terms & Keywords

  • tPA Alteplase, Acute Ischemic Stroke, NINDS trial