Infarct volume as a surrogate or auxiliary outcome measure in ischemic stroke clinical trials

Background and Purpose - Reduction in infarct volume is the standard measur e of therapeutic success in animal stroke models, Reduction in infarct volu me has been advocated as a biological surrogate or auxiliary outcome measur e for human stroke clinical trials to replace or supplement deficit, disabi lity, and global clinical scales. However, few studies have investigated co rrelations 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 i n Patients With Acute Stroke (RANTTAS). Patients were enrolled within 6 hou rs of onset of stroke in any vessel distribution. Infarct volume was measur ed by operator-assisted computerized planimetry. Results - One hundred thirty-two patients had visible new supratentorial in farcts, with median infarct volume of 28.0 cm(3) (interquartile range, 9.0 to 93.0 cm(3)), Fifty-nine patients had no visible new infarct. Correlation s with standard 3-month outcome scales and mortality were as follows: Barth el 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 a lone, 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 as sessment scales. The modesty of this linkage constrains the use of infarct volume as a surrogate end point in ischemic stroke clinical trials.