Abstract
Abstract TMP115: Technical Feasibility and Protocol Compliance in the Second Stroke Pre-Clinical Assessment Network
Stroke (1970), Vol.56(Suppl_1)
02/2025
DOI: 10.1161/str.56.suppl_1.TMP115
Abstract
Abstract only Background/Aims: The Stroke Preclinical Assessment Network (SPAN) is a randomized, placebo-controlled, blinded, multi-laboratory preclinical study using a Multi-Arm Multi-Stage statistical design to select one or more putative stroke treatments with an implied high likelihood of success in future human clinical stroke trials. Methods: Through a rigorous NIH-managed peer review process, six independent research laboratories were selected for testing five promising cerebrovascular interventions. A Coordinating Center at the University of Southern California leads the trial. The Interventions, also selected through an NIH peer review process, included NanO2 (NuvOx) an oxygen delivery emulsion, tatCN19o (Neurexis) a CaM-kinase II inhibitor, GSK2256098 (GlaxoSmithKline/ETSU) a focal adhesion kinase inhibitor, GSK2256294 (GlaxoSmithKline/OHSU) a soluble epoxide hydrolase inhibitor, and BPN-27332 (Loxagen/MGH) a lipoxygenase inhibitor. After a pilot trial to evaluate several behavioral measures, we designated the primary endpoint for SPAN 2 to be a multi-item functional test battery, the Simplified SPAN Score. All other procedures, including behavior tests and magnetic resonance imaging were performed as they were in SPAN 1. Per the SPAN 2 pre-specified protocol, an interim analysis was performed after Stage 1, aka, SPAN 2.1. Results: SPAN 2.1 enrolled 774 subjects, divided among 4 animal co-morbid models in whom a transient filament MCAo was performed: young healthy mice (n=193), diet-induced obese mice (n=197), aged mice (n=192), and spontaneously hypertensive rats (192). Nine subjects were found ineligible, leaving an ITT population of 765, of whom 13 were dropped during the stroke procedure—the primary analysis population (mITT) included 751 subjects. Protocol compliance was evaluated: over 99% of subjects received the correct assigned intervention, but dose timing was protocol adherent in only 61%. Animals who did not receive all assigned doses (n=100) were excluded, leaving a Full Treatment population of 651. Mortality after treatment included 158 subjects, 21% of the mITT group. Among the animal comorbid models, mortality was greatest (40%) in aged mice. Conclusions: The feasibility and protocol compliance seen in SPAN 1 have been replicated in stage 1 of the second trial, SPAN 2.1. Mortality resembles previous experience, with an improved survival in aged mice. SPAN 2 has advanced to Stage 2 where improved dose timing is implemented.
Details
- Title: Subtitle
- Abstract TMP115: Technical Feasibility and Protocol Compliance in the Second Stroke Pre-Clinical Assessment Network
- Creators
- Patrick Lyden - LAC+USC Medical CenterJenny Johnson - NuvOx PharmaEvan Unger - NuvOx PharmaTheo Hagg - East Tennessee State UniversityKlaus van Leyen - Massachusetts General HospitalNabil Alkayed - Oregon Health & Science UniversityRobyn Goforth - Neurexis Therapeutics, Aurora, Colorado, United StatesMarcio Diniz - Icahn School of Medicine at Mount SinaiKirsten Lynch - USC, Los Angeles, California, United StatesKarni Bedirian - Icahn School of Medicine at Mount SinaiJessica Lamb - LAC+USC Medical CenterKarisma Nagarkatti - LAC+USC Medical CenterBingren Hu - University of California, San DiegoYamileck Olivas Garcia - University of California, San DiegoYingxin Chen - University of California, San DiegoChunli Liu - University of California, San DiegoHuaxin Sheng - Duke Medical Centershasha zhang - Duke Medical CenterHaichen Wang - Duke Medical CenterWyatt Austin - Duke Medical CenterCynthia Flores - Duke Medical CenterWei Yang - Duke UniversityDavid Hess - Augusta UniversityMohammad B. Khan - Augusta University HealthPradip Kamat - Augusta University HealthShahneela Siddiqui - Augusta University HealthKrishnan Dhandapani - Augusta University HealthAli Arbab - Augusta University HealthCenk Ayata - MGH Harvard, Charlestown, Massachusetts, United StatesAndreia Morais - Massachusetts General HospitalTakahiko Imai - Massachusetts General HospitalXUYAN Jin - Massachusetts General HospitalLauren Sansing - Yale UniversityLigia Braga Boisserand - University of New HavenSandeep Kumar Mishra - Yale UniversityPinar Caglayan - Yale UniversityStacy Guan - University of New HavenBasavaraju Sanganahalli - Yale UniversityFahmeed Hyder - Yale UniversityEnrique Leira - University of IowaAnil Chauhan - University of IowaRakeshkumar Patel - University of Iowa, Internal MedicineMariia Kumskova - University of IowaAbhishek Jha - University of IowaAditi Jain - University of Iowa, Internal MedicineVitalii Kuznetsov - University of Iowa, IOWA city, Iowa, United States
- Resource Type
- Abstract
- Publication Details
- Stroke (1970), Vol.56(Suppl_1)
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- DOI
- 10.1161/str.56.suppl_1.TMP115
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Language
- English
- Date published
- 02/2025
- Academic Unit
- Neurology; Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9984786280002771
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