Multilaboratory, Blinded, Randomized Trial of Five Cerebroprotectants in Ischemic Stroke.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Ayata Cenk, Chauhan Anil K, Hess David C, Hu Bingren, Leira Enrique C, Sansing Lauren, Sheng Huaxin, Imai Takahiko, Jin Xuyan, Aykan Sanem A, Morais Andreia, Jha Abhishek B, Jain Aditi, Thedens Daniel, Patel Rakesh B, Kumskova Mariia, Khan Mohammad B, Dhandapani Krishnan M, Kamat Pradip K, Arbab Ali S, Olivas Garcia Yamileck, Asadi Yasin, Liu Chunli, Sauer Kaley, Chen Yingxin, Boisserand Ligia S B, Caglayan Pinar, Guan Qinyue Stacy, Hyder Fahmeed, Martin J, Gade Sanjana, Sanganahalli Basavaraju G, Mishra Sandeep Kumar, Yang Wei, Wang Haichen, Zhang Shasha, Wetsel William, Johnson G Allan, Bedirian Karni, Wang Shu-Hsiang, Diniz Marcio A, Lynch Kirsten, Bienkowski Michael, Toga Arthur W, Nagarkatti Karisma, Lamb Jessica, Lyden Patrick
Аннотация
METHODS: The SPAN (Stroke Preclinical Assessment Network) consists of 6 research laboratories performing the experiments and 1 coordinating center at which treatments are prepared in a blinded manner, subjects are randomized, and statistical analysis is performed. We conducted a rigorous trial that included both sexes, multiple comorbidities, randomization, concealment of treatment status, blinded outcome assessments, prespecified sample sizes, and comprehensive data tracking. Five promising treatments were evaluated: BPN-27332, a lipoxygenase inhibitor; uric acid, a potent natural scavenger of free radicals; tatCN19o, a peptide inhibitor of activated CaMKII (Ca2+/CaM-dependent protein kinase II); GSK2256294, an inhibitor of sEH (soluble epoxide hydrolase); and NVX-058, an oxygen-carrying compound. A behavioral battery was selected as the end point for the primary analysis. The primary analysis used the modified intention-to-treat population.
RESULTS: In total, 1768 rodents (882 females and 886 males) were enrolled: 441 young healthy mice, 444 aging mice, 450 mice with obesity-induced hyperglycemia and metabolic syndrome, and 433 spontaneously hypertensive rats. Data missing due to death before 30 days of follow-up were imputed from the same treatment group, animal model, sex, and stage. Although none of the candidates met the prespecified efficacy boundary, GSK2256294 showed an odds ratio for benefit of 1.28 (95% CI, 0.99-1.65), which was significant at P<0.05.
CONCLUSIONS: The second SPAN study reaffirms the importance and feasibility of rigorous, multilaboratory preclinical testing networks to potentially reduce false positives in the development pipeline.