(Stroke. 1999;30:293-298.)
© 1999 American Heart Association, Inc.
Original Contributions |
Infarct Volume as a Surrogate or Auxiliary Outcome Measure in Ischemic Stroke Clinical Trials
Presented in part at the 121st Annual Meeting of the American Neurological Association, Miami, Fla, October 13–16, 1996.
From the Stroke Center and Department of Neurology, University of California, Los Angeles (J.L.S.); the Department of Neurology, University of Virginia (Charlottesville) (K.C.J., L.L.T., E.C.H.); the Department of Neurology, Northwestern Medical School, Evanston, Ill (D.H.); the Department of Neurology, Johns Hopkins University, Baltimore, MD (R.W.); and the Department of Neurology, Harvard Medical School, Boston, Mass (W.K.).
Correspondence to Jeffrey L. Saver, MD, UCLA Stroke Center, Reed Neurologic Research Center, 710 Westwood Plaza, Los Angeles, CA 90095. E-mail jsaver{at}ucla.edu
Background and Purpose—Reduction in infarct volume is the standard measure of therapeutic success in animal stroke models. Reduction in infarct volume has been advocated as a biological surrogate or auxiliary outcome measure for human stroke clinical trials to replace or supplement deficit, disability, and global clinical scales. However, few studies have investigated correlations between infarct volume and clinical end points in acute ischemic stroke patients.
Methods—CT scans at days 6 to 11 were acquired prospectively in 191 fully eligible patients enrolled in the Randomized Trial of Tirilazad Mesylate in Patients With Acute Stroke (RANTTAS). Patients were enrolled within 6 hours of onset of stroke in any vessel distribution. Infarct volume was measured by operator-assisted computerized planimetry.
Results—One hundred thirty-two patients had visible new supratentorial infarcts, with median infarct volume of 28.0 cm3 (interquartile range, 9.0 to 93.0 cm3). Fifty-nine patients had no visible new infarct. Correlations with standard 3-month outcome scales and mortality were as follows: Barthel Index, r=0.43; Glasgow Outcome Scale, r=0.53; National Institutes of Health Stroke Scale, r=0.54; mortality, r=0.31. For visible infarcts alone, correlations were as follows: BI, r=0.46; GOS, r=0.59; NIHSS, r=0.56; mortality, r=0.32.
Conclusions—Subacute CT infarct volume correlates moderately with 3-month clinical outcome as assessed by widely used neurological and functional assessment scales. The modesty of this linkage constrains the use of infarct volume as a surrogate end point in ischemic stroke clinical trials.
Key Words: cerebral infarction • clinical trials • stroke assessment • stroke outcome • tomography, x-ray computed
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