Abstract

The ALIAS Trial (Albumin In Acute Stroke) is a randomized, double-blind, placebo-controlled, multicenter, Phase III clinical trial of high-dose human albumin (ALB) therapy for neuroprotection in acute ischemic stroke. The Trial builds upon extensive preclinical evidence that high-dose ALB is markedly neuro- protective; and our ongoing NIH-funded Phase I ALB Dose-Escalationand Safety Clinical Trial, which has completed the fifth of the six pre-specified ALB dose-tiers (total of 70 subjects) and has shown that the higher doses can be safely administered without ALB-related toxicity and with strong suggestions of efficacy. Significantly, dose-tier V (1.71 g/kg) falls well within the per-kg dose-range of 1.25-2.50 g/kg shown in preclinical studies to be highly protective; The primary aim of the ALIAS Phase III Trial is to ascertain whether high-dose ALB therapy, compared to saline-placebo, will increase the proportion of favorable outcome in subjects with acute ischemic stroke. To this end, we propose to conduct two separate but concurrently implemented randomized, double-blinded trials of ALB therapy in patients with acute ischemic stroke whose baseline NIH Stroke Scale Score (NIHSSS) is 6 or greater and who can be treated with ALB within 5 hours of stroke-onset. The two trials will be carried out in two cohorts: one that receives standard-of-caretreatment with i.v. tPA; and one that does not receive tPA. Decision regarding tPA therapy is based on the local best standard of care.' The primary hypothesis will be tested separately in each cohort. Favorable outcome is defined as either an NIHSSS of 0 or 1, or a modified Rankin Score (mRS)ofOor 1, or both, measured at 3 months from randomization. The trials will incorporate interim analyses, and a maximum of 1,800 subjects will be recruited at 40 clinical sites in the U.S. and Canada. The ALIAS Trial affords the unique opportunity to apply a preclinically highly effective strategy to treat stroke using a dose and timing that closely replicate the experimental setting in which efficacy was shown.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01NS054630-03S1
Application #
7544875
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Gilbert, Peter R
Project Start
2005-09-15
Project End
2010-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
3
Fiscal Year
2008
Total Cost
$21,900
Indirect Cost

  Institution

Name
Medical University of South Carolina
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425

  Publications

Fan, Liqiong; Yeatts, Sharon D; Wolf, Bethany J et al. (2018) The impact of covariate misclassification using generalized linear regression under covariate-adaptive randomization. Stat Methods Med Res 27:20-34
Nowacki, Amy S; Zhao, Wenle; Palesch, Yuko Y (2017) A surrogate-primary replacement algorithm for response-adaptive randomization in stroke clinical trials. Stat Methods Med Res 26:1078-1092
Martin, Renee' H; Yeatts, Sharon D; Hill, Michael D et al. (2016) ALIAS (Albumin in Acute Ischemic Stroke) Trials: Analysis of the Combined Data From Parts 1 and 2. Stroke 47:2355-9
Lees, Kennedy R; Selim, Magdy H; Molina, Carlos A et al. (2016) Early Versus Late Assessment of Stroke Outcome. Stroke 47:1416-9
Weng, Yanqiu; Palesch, Yuko Y; DeSantis, Stacia M et al. (2016) Assessing the impact of safety monitoring on the efficacy analysis in large Phase III group sequential trials with non-trivial safety event rate. J Biopharm Stat 26:672-85
Al-Ali, Firas; Elias, John J; Tomsick, Thomas A et al. (2015) Relative Influence of Capillary Index Score, Revascularization, and Time on Stroke Outcomes From the Interventional Management of Stroke III Trial. Stroke 46:1590-4
Zhao, Wenle; Hill, Michael D; Palesch, Yuko (2015) Minimal sufficient balance-a new strategy to balance baseline covariates and preserve randomness of treatment allocation. Stat Methods Med Res 24:989-1002
Adeoye, Opeolu; Sucharew, Heidi; Khoury, Jane et al. (2015) Recombinant tissue-type plasminogen activator plus eptifibatide versus recombinant tissue-type plasminogen activator alone in acute ischemic stroke: propensity score-matched post hoc analysis. Stroke 46:461-4
Broderick, Joseph P; Berkhemer, Olvert A; Palesch, Yuko Y et al. (2015) Endovascular Therapy Is Effective and Safe for Patients With Severe Ischemic Stroke: Pooled Analysis of Interventional Management of Stroke III and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands Stroke 46:3416-22
Zhao, Wenle; Mu, Yunming; Tayama, Darren et al. (2015) Comparison of statistical and operational properties of subject randomization procedures for large multicenter clinical trial treating medical emergencies. Contemp Clin Trials 41:211-8

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