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Updated: Jul 20, 2026
A Magnetic Resonance Imaging Protocol for Stroke Onset Time Estimation in Permanent Cerebral Ischemia
Published on: September 16, 2017
Proof-of-principle phase II MRI studies in stroke: sample size estimates from dichotomous and continuous data
Background And Purpose:
Since the failure of a number of phase III trials of neuroprotection in ischemic stroke, the need for smaller phase II studies with MRI surrogates has emerged. There is, however, little information available about sample size requirements for such phase II trials and rarely enough patients in single studies to make robust estimates. We have formed an international collaborative group to assemble larger datasets and from these have generated sample size tables for MRI-based infarct expansion as the outcome measure.
Methods:
Twelve centers from Australia, Europe, and North America contributed data from patients with hemispheric ischemic stroke. Infarct expansion was defined from initial diffusion-weighted images and later fluid-attenuated inversion recover or T2 images. Sample size estimates were calculated from data on infarct expansion ratios treated as dichotomous or continuous variables. A nonparametric approach was used because the distribution of infarct expansion was resistant to all forms of transformation.
Results:
As an example, a 20% absolute reduction in infarct expansion ratio (< or = 1), 80% power, and alpha = 0.05 requires 99 patients in each arm. To achieve an equivalent effect size with a continuous approach requires 61 patients.
Conclusions:
These tables will be useful in planning phase II trials of therapy with the use of MRI outcome measures. For positive studies, biologically plausible surrogates such as these may provide a rationale for proceeding to phase III trials.
Insights
This study provides essential sample size tables for planning phase II neuroprotection trials in ischemic stroke using MRI infarct expansion. These estimates aid researchers in designing effective studies with limited patient populations.
Area of Science:
- Neurology
- Radiology
- Clinical Trials
Background:
- Phase III neuroprotection trials for ischemic stroke have frequently failed.
- Smaller phase II studies utilizing MRI surrogates are now needed.
- Limited patient numbers in single studies hinder robust sample size estimation.
Purpose of the Study:
- To generate sample size tables for phase II ischemic stroke trials.
- To utilize MRI-based infarct expansion as a key outcome measure.
- To address the lack of information on sample size requirements for such trials.
Main Methods:
- An international collaborative group pooled data from 12 centers.
- Infarct expansion was measured using diffusion-weighted and later MRI sequences.
- Sample size estimates were calculated using dichotomous and continuous variables with a nonparametric approach.
Main Results:
- Sample size tables were generated for MRI-based infarct expansion.
- For a 20% reduction in infarct expansion ratio (dichotomous), 99 patients per arm are needed (80% power, alpha=0.05).
- A continuous approach requires 61 patients per arm for the same effect size.
Conclusions:
- The generated tables are valuable for planning phase II trials using MRI outcome measures.
- MRI surrogates like infarct expansion can support progression to phase III trials.
- These findings facilitate more efficient and reliable clinical trial design in neuroprotection.
