Stroke Trials Registry

NINDS-tPA
NINDS t-PA Stroke Trial

Principal Investigator
Dr. John Marler

PI Address
Division of Stroke and Trauma
National Institute of Neurologic Disease and Stroke, NIH

Sponsor

Trial Phase:	Phase III
Study Size Actual:	624
Max Time from onset:	3 Hours

Status:
Trial complete. Results published November of 1995.

Purpose:
To test the potential benefit of t-PA when administered within 3 hours of stroke onset.

Interventions:

Tissue plasminogen activator
Thrombolytic

Year Published: 1995

Design:
Randomized, double-blind trial. The trial had two parts. Part 1 (in which 291 patients were enrolled) tested whether t-PA had clinical activity, as indicated by an improvement of 4 points over base-line values in the score of the National Institutes of Health stroke scale (NIHSS) or the resolution of the neurologic deficit within 24 hours of the onset of stroke. Part 2 (in which 333 patients were enrolled) used a global test statistic to assess clinical outcome at three months, according to scores on the Barthel index, modified Rankin scale, Glasgow outcome scale, and NIHSS.

Inclusion Criteria
Acute ischemic stroke presenting within 3 hours of onset.

Patient Involvement:
Patients were randomized to receive t-PA or placebo and were assessed at either 24 hours or 3 months after stroke onset.

Primary Outcome:
Part 1: clinical activity, as indicated by an improvement of 4 points over base-line values in the score of the National Institutes of Health stroke scale (NIHSS) or the resolution of the neurologic deficit within 24 hours of the onset of stroke.
Part 2: Barthel index, modified Rankin scale, Glasgow outcome scale, and NIHSS.

Results:
In part 1, there was no significant difference between the group given t-PA and that given placebo in the percentages of patients with neurologic improvement at 24 hours, although a benefit was observed for the t-PA group at three months for all four outcome measures. In part 2, the long-term clinical benefit of t-PA predicted by the results of part 1 was confirmed (global odds ratio for a favorable outcome, 1.7; 95 percent confidence interval, 1.2 to 2.6). As compared with patients given placebo, patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales. Symptomatic intracerebral hemorrhage within 36 hours after the onset of stroke occurred in 6.4 percent of patients given t-PA but only 0.6 percent of patients given placebo (P < 0.001). Mortality at three months was 17 percent in the t-PA group and 21 percent in the placebo group (P = 0.30).

Source of Information:
N Engl J Med.1995;333:1581-1587.

Web Links and Publications:

Lack of Clinical Significance of Early Ischemic Changes on Computed Tomography in Acute Stroke.
JAMA. 2001 Dec 12;286(22):2830-2838.

Predicting prognosis after stroke: a placebo group analysis from the National Institute of Neurological Disorders and Stroke rt-PA Stroke Trial.
Neurology. 2000 Oct 10;55(7):952-9.

Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study.
Neurology. 2000 Dec 12;55(11):1649-55

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 Jun 10;340(23):1781-7

Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke. NINDS rt-PA Stroke Study Group.
Neurology 1998 Apr;50(4):883-90

Myths regarding the NINDS rt-PA Stroke Trial: setting the record straight.
Ann Emerg Med 1997 Nov;30(5):676-82

Generalized efficacy of t-PA for acute stroke. Subgroup analysis of the NINDS t-PA Stroke Trial.
Stroke 1997 Nov;28(11):2119-2125

Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA Stroke Study Group.
Stroke 1997 Nov;28(11):2109-2118

This information last updated on: 5/27/2008

Reviewed on: 08/21/2008.

UID: 61