Abstract 92: MRI Patient Selection In Acute Stroke Trials: Implications For Sample Size
Background: MRI selection of patients with acute stroke may reduce the required sample size for randomized controlled trials of interventions aimed at restoring blood flow. The Target Mismatch pattern has been proposed as a MRI-marker that can differentiate patients who are likely to benefit from reperfusion from those who will have no effect from or may be harmed by reperfusion. The Target Mismatch pattern is present in approximately 50% of stroke patients with a middle cerebral artery occlusion who present in the 3-6 hour time-window. The pattern is based on the following PWI and DWI criteria: ratio of Tmax>6s over DWI volume >1.2, difference between Tmax>6s and DWI volume >10ml, and DWI volume <100ml. The aim of this study was to compare the required sample size of acute stroke studies that use MRI selection to that of studies which do not use MRI selection.
Methods: All sample size calculations were based on an alpha of 0.05 in a two-sided test and a desired power of 0.8. MRI patient selection was assumed to be according to Target Mismatch criteria. The primary study outcome was assumed to be good functional outcome, defined as a modified Rankin Scale of 0-2 at 90 days. Other assumptions for the sample size calculations were based on data from the literature and data from the pooled EPITHET-DEFUSE database regarding patients with middle cerebral artery (MCA) occlusions treated up to six hours after symptom onset. The spontaneous reperfusion rate in this population was assumed to be 0.22. For MRI-selected mismatch patients the rate of good functional outcome was assumed to be 0.73 with reperfusion and 0.30 without reperfusion. For unselected patients, the rate of favorable clinical outcome was assumed to be 0.67 with reperfusion and 0.41 without reperfusion.
Results: A trial of an intervention that leads to reperfusion of the MCA in 45% of patients would require 396 patients per group if MRI selection criteria were applied and 1096 patients per group without MRI selection criteria. A trial of an intervention that has a 70% reperfusion rate would require 92 patients in each arm if MRI selection criteria were applied versus 251 patients per arm if patients were enrolled without MRI selection. (see figure)
Conclusion: MRI selection can markedly reduce the required sample size of randomized controlled stroke trials in the delayed time-window. This advantage needs to be balanced against the potential drawbacks of using a MRI-marker as an inclusion criterion for a randomized controlled trial.
- © 2012 by American Heart Association, Inc.