Evidence map›Paper›PMID 42775432›Full record

ArticleCirculation research2026

Multilaboratory, Blinded, Randomized Trial of Five Cerebroprotectants in Ischemic Stroke.

Cenk Ayata, Anil K Chauhan, David C Hess, Bingren Hu, Enrique C Leira, Lauren Sansing, Huaxin Sheng, Takahiko Imai, Xuyan Jin, Sanem A Aykan and 37 more

Abstract read
In one paragraph

Article in Circulation research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

47 authors.

Cenk AyataNeurovascular Research Unit, Department of Neurology, Massachusetts General Hospital (C.A., T.I., X.J., S.A.A., A.M.)., Carver College of Medicine, University of Iowa.ORCID 0000-0002-3644-6042
Anil K ChauhanDepartment of Internal Medicine, Division of Hematology, Oncology and Blood & Marrow Transplantation (A.K.C., A.B.J., A.J., R.B.P., M.K.), Carver College of Medicine, University of Iowa.ORCID 0000-0001-8554-0898
David C HessDepartment of Neurology (D.C.H., M.B.K., P.K.K.), The Medical College of Georgia at Augusta University.ORCID 0000-0002-8345-9153
Bingren HuDepartment of Emergency Medicine (B.H., Y.O.G., A.Y., C.L., K.S., Y.C.), University of California San Diego.ORCID 0000-0003-4002-2784
Enrique C LeiraDepartment of Neurology (E.C.L.), Carver College of Medicine, University of Iowa.ORCID 0000-0003-3695-2946
Lauren SansingDepartment of Neurology, Yale School of Medicine, New Haven, CT (L.S., L.S.B.B., P.C., Q.S.G., J.M., S.G.).ORCID 0000-0002-6898-1680
Huaxin ShengDepartment of Anesthesiology, Neurology and Radiology, Duke University Medical Center, Durham, NC (H.S., W.Y., H.W., S.Z., W.W., G.A.J.).ORCID 0000-0002-4325-2940
Takahiko ImaiNeurovascular Research Unit, Department of Neurology, Massachusetts General Hospital (C.A., T.I., X.J., S.A.A., A.M.)., Carver College of Medicine, University of Iowa.ORCID 0000-0002-4422-2946
Xuyan JinNeurovascular Research Unit, Department of Neurology, Massachusetts General Hospital (C.A., T.I., X.J., S.A.A., A.M.)., Carver College of Medicine, University of Iowa.ORCID 0009-0003-1923-4923
Sanem A AykanNeurovascular Research Unit, Department of Neurology, Massachusetts General Hospital (C.A., T.I., X.J., S.A.A., A.M.)., Carver College of Medicine, University of Iowa.ORCID 0000-0001-7335-5556
Andreia MoraisNeurovascular Research Unit, Department of Neurology, Massachusetts General Hospital (C.A., T.I., X.J., S.A.A., A.M.)., Carver College of Medicine, University of Iowa.ORCID 0000-0002-9351-2552
Abhishek B JhaDepartment of Internal Medicine, Division of Hematology, Oncology and Blood & Marrow Transplantation (A.K.C., A.B.J., A.J., R.B.P., M.K.), Carver College of Medicine, University of Iowa.ORCID 0000-0001-9229-0612
Aditi JainDepartment of Internal Medicine, Division of Hematology, Oncology and Blood & Marrow Transplantation (A.K.C., A.B.J., A.J., R.B.P., M.K.), Carver College of Medicine, University of Iowa.
Daniel ThedensDepartment of Radiology (D.T.), Carver College of Medicine, University of Iowa.ORCID 0000-0002-4704-3185
Rakesh B PatelDepartment of Internal Medicine, Division of Hematology, Oncology and Blood & Marrow Transplantation (A.K.C., A.B.J., A.J., R.B.P., M.K.), Carver College of Medicine, University of Iowa.ORCID 0000-0001-9727-9738
Mariia KumskovaDepartment of Internal Medicine, Division of Hematology, Oncology and Blood & Marrow Transplantation (A.K.C., A.B.J., A.J., R.B.P., M.K.), Carver College of Medicine, University of Iowa.ORCID 0000-0002-2477-3011
Mohammad B KhanDepartment of Neurology (D.C.H., M.B.K., P.K.K.), The Medical College of Georgia at Augusta University.ORCID 0000-0001-8231-1256
Krishnan M DhandapaniDepartment of Neurosurgery (K.M.D.), The Medical College of Georgia at Augusta University.ORCID 0000-0001-7044-1117
Pradip K KamatDepartment of Neurology (D.C.H., M.B.K., P.K.K.), The Medical College of Georgia at Augusta University.ORCID 0000-0002-0376-2284
Ali S ArbabDepartment of Biochemistry and Molecular Biology (A.S.A.), The Medical College of Georgia at Augusta University.ORCID 0000-0003-2902-3671
Yamileck Olivas GarciaDepartment of Emergency Medicine (B.H., Y.O.G., A.Y., C.L., K.S., Y.C.), University of California San Diego.ORCID 0009-0009-0968-7199
Yasin AsadiDepartment of Emergency Medicine (B.H., Y.O.G., A.Y., C.L., K.S., Y.C.), University of California San Diego.
Chunli LiuDepartment of Emergency Medicine (B.H., Y.O.G., A.Y., C.L., K.S., Y.C.), University of California San Diego.
Kaley SauerDepartment of Emergency Medicine (B.H., Y.O.G., A.Y., C.L., K.S., Y.C.), University of California San Diego.
Yingxin ChenDepartment of Emergency Medicine (B.H., Y.O.G., A.Y., C.L., K.S., Y.C.), University of California San Diego.
Ligia S B BoisserandDepartment of Neurology, Yale School of Medicine, New Haven, CT (L.S., L.S.B.B., P.C., Q.S.G., J.M., S.G.).ORCID 0000-0002-0058-2894
Pinar CaglayanDepartment of Neurology, Yale School of Medicine, New Haven, CT (L.S., L.S.B.B., P.C., Q.S.G., J.M., S.G.).ORCID 0009-0005-3943-2817
Qinyue Stacy GuanDepartment of Neurology, Yale School of Medicine, New Haven, CT (L.S., L.S.B.B., P.C., Q.S.G., J.M., S.G.).ORCID 0000-0003-4936-8220
Fahmeed HyderDepartment of Radiology & Biomedical Imaging, Yale University, New Haven, CT (F.H., B.G.S., S.K.M.).ORCID 0000-0001-7822-4002
J MartinDepartment of Neurology, Yale School of Medicine, New Haven, CT (L.S., L.S.B.B., P.C., Q.S.G., J.M., S.G.).
Sanjana GadeDepartment of Neurology, Yale School of Medicine, New Haven, CT (L.S., L.S.B.B., P.C., Q.S.G., J.M., S.G.).ORCID 0009-0006-7499-4660
Basavaraju G SanganahalliDepartment of Radiology & Biomedical Imaging, Yale University, New Haven, CT (F.H., B.G.S., S.K.M.).ORCID 0000-0002-0851-6621
Sandeep Kumar MishraDepartment of Radiology & Biomedical Imaging, Yale University, New Haven, CT (F.H., B.G.S., S.K.M.).ORCID 0000-0002-1016-0206
Wei YangDepartment of Anesthesiology, Neurology and Radiology, Duke University Medical Center, Durham, NC (H.S., W.Y., H.W., S.Z., W.W., G.A.J.).ORCID 0000-0001-5719-4393
Haichen WangDepartment of Anesthesiology, Neurology and Radiology, Duke University Medical Center, Durham, NC (H.S., W.Y., H.W., S.Z., W.W., G.A.J.).
Shasha ZhangDepartment of Anesthesiology, Neurology and Radiology, Duke University Medical Center, Durham, NC (H.S., W.Y., H.W., S.Z., W.W., G.A.J.).ORCID 0009-0005-2946-8648
William WetselDepartment of Anesthesiology, Neurology and Radiology, Duke University Medical Center, Durham, NC (H.S., W.Y., H.W., S.Z., W.W., G.A.J.).ORCID 0000-0002-3592-7397
G Allan JohnsonDepartment of Anesthesiology, Neurology and Radiology, Duke University Medical Center, Durham, NC (H.S., W.Y., H.W., S.Z., W.W., G.A.J.).ORCID 0000-0002-7606-5447
Karni BedirianDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY (K.B., S.-H.W., M.A.D.).
Shu-Hsiang WangDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY (K.B., S.-H.W., M.A.D.).
Marcio A DinizDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY (K.B., S.-H.W., M.A.D.).ORCID 0000-0002-2427-7843
Kirsten LynchLaboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute (K.L., M.B., A.W.T.), Keck School of Medicine of the University of Southern California, Los Angeles.ORCID 0000-0003-3976-5783
Michael BienkowskiLaboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute (K.L., M.B., A.W.T.), Keck School of Medicine of the University of Southern California, Los Angeles.ORCID 0000-0002-8231-8893
Arthur W TogaLaboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute (K.L., M.B., A.W.T.), Keck School of Medicine of the University of Southern California, Los Angeles.ORCID 0000-0001-7902-3755
Karisma NagarkattiDepartment of Physiology and Neuroscience, Zilkha Neurogenetic Institute of the Keck School of Medicine of the University of Southern California, Los Angeles (M.B., K.N., J.L., P.L.).ORCID 0000-0002-7300-9968
Jessica LambDepartment of Physiology and Neuroscience, Zilkha Neurogenetic Institute of the Keck School of Medicine of the University of Southern California, Los Angeles (M.B., K.N., J.L., P.L.).ORCID 0000-0002-0342-9983
Patrick LydenDepartment of Physiology and Neuroscience, Zilkha Neurogenetic Institute of the Keck School of Medicine of the University of Southern California, Los Angeles (M.B., K.N., J.L., P.L.).ORCID 0000-0001-6170-4042

Funding

The NIH SPAN Coordinating CenterU24NS130600 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LYDEN, PATRICK D · 2023 to 2025
$2.8M
The NIH SPAN Coordinating CenterU24NS113452 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LYDEN, PATRICK D · 2019 to 2021
$2.4M
Y-SPAN: Yale Translational Cerebroprotection Program in SPANU01NS130585 · NINDS · YALE UNIVERSITY · PI SANSING, LAUREN H · 2023 to 2025
$1.9M
Stroke Preclicinal Assessment NetworkU01NS130588 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI AYATA, CENK · 2023 to 2025
$1.9M
Testing Cerebroprotective Interventions with Rodent Ischemic Stroke ModelsU01NS130557 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HU, BINGREN · 2023 to 2025
$1.8M
Augusta SPAN 2U01NS130590 · NINDS · AUGUSTA UNIVERSITY · PI DHANDAPANI, KRISHNAN M., HESS, DAVID C. · 2023 to 2025
$1.8M
Duke Testing Site for Stroke Preclinical Assessment NetworkU01NS130598 · NINDS · DUKE UNIVERSITY · PI SHENG, HUAXIN, YANG, WEI · 2023 to 2025
$1.7M
The University of Iowa Stroke Preclinical Assessment Center for Neuroprotection in strokeU01NS113388 · NINDS · UNIVERSITY OF IOWA · PI CHAUHAN, ANIL KUMAR, LEIRA, ENRIQUE CARLOS · 2019 to 2021
$1.1M
USC Neurosurgery Research and Education Training ProgramUE5NS099008 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI William J Mack · 2024 to 2026
$126k
NINDS NIH HHS U01 NS113388NINDS NIH HHS U01 NS130557NINDS NIH HHS U01 NS130585NINDS NIH HHS U01 NS130588NINDS NIH HHS U01 NS130590NINDS NIH HHS U01 NS130598NINDS NIH HHS U24 NS113452NINDS NIH HHS U24 NS130600NINDS NIH HHS UE5 NS099008
6 · The paper itself

Abstract

backgroundNegative clinical trials foster therapeutic nihilism and public skepticism, especially if they follow optimistic preclinical results. One way to increase the likelihood of successful clinical trials is to enhance the preclinical testing of new treatments. Recently, multicenter preclinical testing networks have gained attention as one tool to enhance rigor and reduce the likelihood of erroneously recommending a new candidate treatment for advancement to clinical trial testing.

methodsThe 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 (Ca

resultsIn 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

conclusionsThe second SPAN study reaffirms the importance and feasibility of rigorous, multilaboratory preclinical testing networks to potentially reduce false positives in the development pipeline.

Indexed as

ischemialipoxygenase inhibitormetabolic syndromeneuroprotectionstroke

Identifiers

PMID42775432
PMCPMC13602274

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.