Infarct volume as a surrogate or auxiliary outcome measure in ischemic stroke clinical trials. The RANTTAS Investigators.

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.