Effect of intravenous recombinant tissue plasminogen activator on ischemicstroke lesion size measured by computed tomography

Background and Purpose-When given within 3 hours of symptom onset, recombin ant tissue plasminogen activator (rtPA) improves outcome 3 months after isc hemic stroke. Prespecified secondary end points of the National Institute o f Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial were CT lesi on 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 IT, 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 i ndividual studies were not powered to test for lesion volume differences, d ata from both parts of the trial were combined for all analyses. The primar y analysis was conducted with the use of an intention-to-treat algorithm (i ncluding patients who died or were lost to follow-up). Measured lesion volu me (excluding deaths and those lost to follow-up) was used as a secondary o utcome in an exploratory analysis. Results-After tPA treatment, there was a trend toward a reduction in 3-mont h median lesion volume in the tPA group: 15 cm(3) (interquartile range, 2 t o 87) compared with 24 cm3 (interquartile range, 4 to 101) in the placebo g roup (P=0.06, log model) with a reduction of 11% in cumulative lesion volum e, computed with Smirnov's D statistic. After exclusion of deaths and those lost to follow-up, similar trends toward positive treatment effects were s een at all time points. Conclusions-The direction of the effect of tPA on CT lesion volume at all t ime points was consistent with the observed clinical effects at 3 months. C T lesion volume may not be as sensitive a measure of treatment effect as cl inical evaluation, at least as used in this study. An intention-to-treat an alysis for the radiographic end point in this acute ischemic stroke clinica l trial is a less biased approach to account for missing radiographic data than an analysis that uses only measured radiological data.