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Updated: Jul 12, 2025
Histological Quantification of Chronic Myocardial Infarct in Rats
Published on: December 11, 2016
Clinically important effect sizes for clinical trials using infarct growth reduction as the primary outcome: a
Nien-Chen Liao1,2, Mersedeh Bahr Hosseini3, Jeffrey L Saver4
1Neurology, Taichung Veterans General Hospital, Taichung, Taiwan.
Background:
Infarct growth on multimodal imaging is a common lead outcome in phase 2 proof-of-concept and dose-optimization neuroprotective agent stroke trials. However, the effect size in infarct growth reduction that correlates with clinically meaningful differences in clinical global disability outcomes has not been well delineated.
Methods:
A systematic literature search identified all endovascular thrombectomy randomized trials reporting magnitude of treatment effect on both infarct growth reduction and increase in functional independence (modified Rankin Scale (mRS) 0-2). Data aggregation determined the size of infarct growth reductions salient to four types of clinically meaningful effect sizes of increase in functional independence: (1) the minimal clinically important difference (MCID)-outcome specific; (2) the MCID-practice changing; (3) the realistic target difference; and (4) the reasonable comparability effect size.
Results:
A systematic search identified four trials enrolling 612 imaged participants. Across the trials, the amount of functional independence (mRS 0-2) increase associated with each 1 mL reduction in infarct growth was mean 2.3±0.6%. An infarct growth reduction of 0.57 mL correlated with the mRS 0-2 increase MCID of 1.3%. Infarct growth reductions of 2.27 mL, 4.35 mL, and 6.53 mL correlated with realistic effect and reasonable comparability effects sizes of mRS 0-2 increases of 5%, 10%, and 15%, respectively.
Conclusion:
In formal meta-analysis of randomized treatment trials, every 1 mL reduction in infarct growth was associated with a 2.3% increase in functional independence (mRS 0-2) at 3 months. This conversion factor can inform selection of infarct growth effect size targets for phase 2 trials of neuroprotective agents.
Insights
Reducing infarct growth in stroke trials significantly improves functional independence. A 1 mL infarct reduction correlates with a 2.3% increase in functional outcomes, guiding neuroprotective agent trial targets.
Area of Science:
- Neuroscience
- Clinical Trials
- Medical Imaging
Background:
- Infarct growth is a key outcome in neuroprotective stroke trials.
- The link between infarct growth reduction and clinical disability outcomes is unclear.
Purpose of the Study:
- To determine the effect size of infarct growth reduction correlating with clinically meaningful improvements in functional independence.
- To establish a conversion factor for infarct growth reduction to functional independence gains in stroke trials.
Main Methods:
- Systematic literature search of endovascular thrombectomy randomized trials.
- Data aggregation to link infarct growth reduction with functional independence (modified Rankin Scale 0-2) effect sizes.
- Analysis of four clinically meaningful effect size categories for functional independence.
Main Results:
- Four trials with 612 participants were analyzed.
- A 1 mL infarct growth reduction correlated with a 2.3% increase in functional independence (mRS 0-2).
- Specific infarct growth reductions (0.57 mL to 6.53 mL) were linked to various clinically meaningful functional independence increases (1.3% to 15%).
Conclusions:
- A meta-analysis of randomized trials shows a 2.3% increase in functional independence for every 1 mL infarct growth reduction.
- This finding provides a crucial conversion factor for setting infarct growth targets in Phase 2 neuroprotective agent trials for stroke.
