A New Paradigm for Neuroprotection Clinical Trials for Acute Ischemic Stroke

• Published in: Translational stroke research Vol. 14; no. 6; pp. 829 - 832
• Main Author: Nemoto, Edwin M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2023; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Brain Ischemia - complications; Brain Ischemia - drug therapy; Cardiology; Clinical trials; Comment; Failure; Humans; Intervention; Ischemia; Ischemic Stroke; Magnetic resonance imaging; Neurology; Neuroprotection; Neurosciences; Neurosurgery; Stroke; Stroke - drug therapy; Vascular Surgery; Veins & arteries
• ISSN: 1868-4483; 1868-601X
• DOI: 10.1007/s12975-022-01091-8

A review in 2020 [6] evaluated preclinical and phase 1–3 clinical trials using an inverted funnel statistical method to identify the frequency of unpublished reports and publication bias, and concluded, “Pivotal study design differences between experimental studies and clinical trials, including different primary end points and time to treatment, publication bias, neglected quality criteria and low power, contribute to the decline in efficacy in stroke treatments from experimental studies to phase 3 clinical trials.” Justification for the SPAN initiative is that “Unlike most preclinical studies, randomized clinical trials, the gold standard in clinical drug development, require large sample sizes, randomization, proper controls such as a placebo, blinded assessment of outcomes, and stringent data analysis and reporting” [9]. Qualification for Thrombolysis and Endovascular Arterial Thrombectomy Intervention in AIS Neuroprotection clinical trials in AIS in animals and their evaluation in clinical trials evolved over decades in parallel with the development of Food and Drug Administration (FDA)–approved recombinant tissue plasminogen activator (rTPA) thrombolysis and endovascular arterial thrombectomy (EAT) treatments. EAT and rTPA thrombolysis imaging guidelines were established in the DEFUSE3 [17] study including proximal middle cerebral artery or internal carotid artery occlusion, infarct size of < 70 ml, and a PWI/DWI volume ratio of 1.8 or more.