Rani G Sah1,2,3,4, Christopher D d'Esterre1,2,3,4,5, Michael D Hill1,2,3,4, Moiz Hafeez1,2, Sana Tariq2,3, Nils D Forkert3,5, Richard Frayne2,3,4,5, Andrew M Demchuk1,2,3,4, Mayank Goyal1,2,3,5, Philip A Barber1,2,3,5. 1. 1 Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Canada. 2. 2 Seaman Family Centre, Foothills Medical Centre, Calgary, Canada. 3. 3 Hotchkiss Brain Institute, University of Calgary, Calgary, Canada. 4. 4 Department of Clinical Neurosciences, University of Calgary, Calgary, Canada. 5. 5 Department of Radiology, University of Calgary, Calgary, Canada.
Abstract
BACKGROUND: A proportion of patients presenting with acute small ischemic strokes have poor functional outcomes, even following rapid recanalization treatment. AIMS: Infarct growth may occur even after successful recanalization and could represent an appropriate endpoint for future stroke therapy trials. METHODS: Magnetic resonance diffusion-weighted imaging lesion volumes were obtained at 5 h (initial posttreatment) and 24 h (follow-up) after acute stroke treatment for n = 33 in ischemic stroke patients. Sample sizes per arm (90% power, 30% effect size) for diffusion-weighted imaging lesion growth between initial and 24 h, early change in the National Institutes of Health Stroke Scale between pre- and 24 h, National Institutes of Health Stroke Scale at 24 h, and diffusion-weighted imaging lesion volume at 24 h were estimated to power a placebo-controlled stroke therapy trial. RESULTS: For patients with poor recanalization (modified thrombolysis in cerebral infarction <2 a; modified arterial occlusion lesion = 0-2) (n = 11), the median diffusion-weighted imaging lesion growth was 8.1 (interquartile range: 4.5, 22.4) ml and with good recanalization (modified thrombolysis in cerebral infarction =2 b or 3; modified arterial occlusion lesion = 3) (n = 22), the median diffusion-weighted imaging lesion growth was 10.0 (interquartile range: 6.0, 28.2) ml ( P = 0.749). When considering a 30% effect size, the sample size required per arm to achieve significance in an acute stroke study would be: (1) N = 49 for the diffusion-weighted imaging lesion growth between initial posttreatment and follow-up time points, (2) N = 65 for the change in the National Institutes of Health Stroke Scale between admission and 24 h, (3) N = 259 for the National Institutes of Health Stroke Scale at 24 h, and (4) N = 256 for diffusion-weighted imaging volume at 24 h. CONCLUSION: Despite best efforts to recanalize the ischemic brain, early diffusion-weighted imaging lesion growth still occurs. Treatment trials in stroke should consider early diffusion-weighted imaging lesion growth as a surrogate outcome measure to significantly reduce sample sizes.
BACKGROUND: A proportion of patients presenting with acute small ischemic strokes have poor functional outcomes, even following rapid recanalization treatment. AIMS: Infarct growth may occur even after successful recanalization and could represent an appropriate endpoint for future stroke therapy trials. METHODS: Magnetic resonance diffusion-weighted imaging lesion volumes were obtained at 5 h (initial posttreatment) and 24 h (follow-up) after acute stroke treatment for n = 33 in ischemic strokepatients. Sample sizes per arm (90% power, 30% effect size) for diffusion-weighted imaging lesion growth between initial and 24 h, early change in the National Institutes of Health Stroke Scale between pre- and 24 h, National Institutes of Health Stroke Scale at 24 h, and diffusion-weighted imaging lesion volume at 24 h were estimated to power a placebo-controlled stroke therapy trial. RESULTS: For patients with poor recanalization (modified thrombolysis in cerebral infarction <2 a; modified arterial occlusion lesion = 0-2) (n = 11), the median diffusion-weighted imaging lesion growth was 8.1 (interquartile range: 4.5, 22.4) ml and with good recanalization (modified thrombolysis in cerebral infarction =2 b or 3; modified arterial occlusion lesion = 3) (n = 22), the median diffusion-weighted imaging lesion growth was 10.0 (interquartile range: 6.0, 28.2) ml ( P = 0.749). When considering a 30% effect size, the sample size required per arm to achieve significance in an acute stroke study would be: (1) N = 49 for the diffusion-weighted imaging lesion growth between initial posttreatment and follow-up time points, (2) N = 65 for the change in the National Institutes of Health Stroke Scale between admission and 24 h, (3) N = 259 for the National Institutes of Health Stroke Scale at 24 h, and (4) N = 256 for diffusion-weighted imaging volume at 24 h. CONCLUSION: Despite best efforts to recanalize the ischemic brain, early diffusion-weighted imaging lesion growth still occurs. Treatment trials in stroke should consider early diffusion-weighted imaging lesion growth as a surrogate outcome measure to significantly reduce sample sizes.
Authors: Christopher D d'Esterre; Rani Gupta Sah; Zarina Assis; Aron S Talai; Andrew M Demchuk; Michael D Hill; Mayank Goyal; Ting-Yim Lee; Nils D Forkert; Philip A Barber Journal: Br J Radiol Date: 2020-09-17 Impact factor: 3.039
Authors: F Bala; J Ospel; B Mulpur; B J Kim; J Yoo; B K Menon; M Goyal; C Federau; S-I Sohn; M S Hussain; M A Almekhlafi Journal: AJNR Am J Neuroradiol Date: 2021-06-03 Impact factor: 4.966