Effect of intravenous recombinant tissue plasminogen activator on ischemic stroke lesion size measured by computed tomography. NINDS; The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study Group.
Background and Purpose-When given within 3 hours of symptom onset, recombinant tissue plasminogen activator (rtPA) improves outcome 3 months after ischemic stroke. Prespecified secondary end points of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial were CT lesion volumes in the 2 treatment groups (tPA and placebo) at 24 hours, 7 to 10 days, and 3 months after stroke.


METHODS
-The trial included 2 independent studies, part I and part II, with identical methods of data collection. Before part I, uniform standards were established for CT scanning. CT images were obtained at baseline, 24 hours, 7 to 10 days, and 3 months after stroke onset and were reviewed centrally by reviewers blinded to treatment group and clinical findings. Since the individual studies were not powered to test for lesion volume differences, data from both parts of the trial were combined for all analyses. The primary analysis was conducted with the use of an intention-to-treat algorithm (including patients who died or were lost to follow-up). Measured lesion volume (excluding deaths and those lost to follow-up) was used as a secondary outcome in an exploratory analysis.


RESULTS
-After tPA treatment, there was a trend toward a reduction in 3-month median lesion volume in the tPA group: 15 cm(3) (interquartile range, 2 to 87) compared with 24 cm(3) (interquartile range, 4 to 101) in the placebo group (P:=0.06, log model) with a reduction of 11% in cumulative lesion volume, computed with Smirnov's D statistic. After exclusion of deaths and those lost to follow-up, similar trends toward positive treatment effects were seen at all time points.


CONCLUSIONS
-The direction of the effect of tPA on CT lesion volume at all time points was consistent with the observed clinical effects at 3 months. CT lesion volume may not be as sensitive a measure of treatment effect as clinical evaluation, at least as used in this study. An intention-to-treat analysis for the radiographic end point in this acute ischemic stroke clinical trial is a less biased approach to account for missing radiographic data than an analysis that uses only measured radiological data.
D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging*; D002544:Cerebral Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed / Q000706:statistics & numerical data*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010919:Placebos; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator