Abstract T P49: Improving Outcome of Placebo- but not Albumin-Treated Subjects Over the Course of the ALIAS Part 2 Multicenter Trial: Differential Influence of Thrombolytic Therapy
In the ALIAS2 Trial, 841 subjects were randomized 1:1 to treatment with either 25% albumin (ALB, 2 g/kg) or normal saline within 5 hours of stroke onset, and the primary outcome (NIHSS 0-1 and/or modified Rankin scale 0-1) was assessed at 90 days. While overall outcomes did not differ by treatment (44% for both groups), we observed a steadily improving favorable rate in the saline-placebo arm but not in the ALB arm over the trial’s 3.5 year course. This was further analyzed here.
Methods and Findings: Logistic regression confirmed a significant randomization-order x treatment interaction (p<0.001). Thus, at the first pre-specified interim analysis of N=275 subjects, favorable outcome was seen in 44.8% with ALB but only 30.3% with saline (relative benefit 1.48, p=0.0028), while at the second interim analysis of N=550 subjects, the saline rate had risen to 37.5% while the ALB rate remained steady at 44.6% (relative benefit 1.21, p=0.0176). This trend-over-time in saline subjects was highly significant (Jonckheere-Terpstra (J-T) test, p=0.001; Pearson coefficient r=0.792), but there was no such trend in ALB subjects (J-T p=1.000). Simulation analysis confirmed that the saline trend could not have arisen by chance (p=0.0007). Importantly, intravenous tPA use also increased significantly during the trial in both ALB and saline subjects (initial rate 74%, final rate 95%, p<0.0001). Separate logistic regression analyses revealed a highly significant effect of IV tPA use on outcome in saline subjects (odds ratio 2.8, 95% CI 1.5-5.3, p=0.001) but only a marginal effect in ALB subjects (odds ratio 1.7, p=0.06).
Conclusion: ALB treatment appears to have conferred a stable (and desirable) therapeutic “ceiling effect” throughout the trial (in the absence of significant toxicity), while saline subjects (who were unable to benefit from ALB) were susceptible to improved outcome from increasing tPA use as the trial progressed.
Author Disclosures: M.D. Ginsberg: None. M.D. Hill: None. C.S. Moy: None. W.G. Barsan: None. D. Tamariz: None. K.J. Ryckborst: None.
- © 2014 by American Heart Association, Inc.