Skip to main content
Article thumbnail
Location of Repository

NXY-059 for the treatment of acute stroke: pooled analysis of the SAINT I and II trials

By H.C. Diener, K.R. Lees, P. Lyden, J. Grotta, A. Davalos, S.M. Davis, A. Shuaib, T. Ashwood, W. Wasiewski, V. Alderfer, H.G. Hardemark and L. Rodichok

Abstract

<p><b>Background and Purpose:</b> In animal models of acute ischemic stroke (AIS), the free radical-trapping agent NXY-059 showed promise as a neuroprotectant. SAINT I and II were randomized, placebo-controlled, double-blind trials to investigate the efficacy of NXY-059 in patients with AIS.</p>\ud \ud <p><b>Methods:</b> Patients with AIS received an infusion of intravenous NXY-059 or placebo within 6 hours from the onset of stroke symptoms. A pooled individual patient analysis was prespecified to assess the overall efficacy and to examine subgroups. The primary end point was the distribution of disability scores measured on the modified Rankin scale (mRS) at 90 days. Neurologic and activities of daily living scores were investigated as secondary end points. We also evaluated whether treatment with NXY-059 would reduce alteplase-related intracranial hemorrhages. Finally, we evaluated possible predictors of good or poor outcome.</p>\ud \ud <p><b>Results:</b> An intent-to-treat efficacy analysis was based on 5028 patients. Baseline parameters and prognostic factors were well balanced between treatment groups. The distribution of scores on the mRS was not different in the group treated with NXY-059 (n = 2438) compared with the placebo group (n = 2456): odds ratio for limiting disability = 1.02; 95% CI, 0.92 to 1.13 (P = 0.682, Cochran-Mantel-Haenszel test). Comparisons at each level of the mRS confirmed an absence of benefit. There was no evidence of efficacy in prespecified subgroups or from the secondary outcome analyses. Mortality was equal in the 2 groups (16.7% vs 16.5%), and adverse event rates were similar. Among patients treated with alteplase, there was no decrease in rates of symptomatic or asymptomatic hemorrhage associated with NXY-059 treatment versus placebo. Subgroup analyses identified National Institutes of Health Stroke Scale score, age, markers of inflammation, blood glucose, and right-sided infarct as predictors of poor outcome.</p>\ud \ud <p><b>Conclusions:</b> NXY-059 is ineffective for treatment of AIS within 6 hours of symptom onset. This is also true for subgroups and the prevention of alteplase-associated hemorrhage.</p

Publisher: American Heart Association
Year: 2008
OAI identifier: oai:eprints.gla.ac.uk:17914
Provided by: Enlighten

Suggested articles

Citations

  1. (2006). 1,026 experimental treatments in acute stroke. Ann Neurol. doi
  2. (2008). A critical appraisal of the NXY-059 neuroprotection studies for acute stroke: a need for more rigorous testing of neuroprotective agents in animal models of stroke. doi
  3. Additional outcomes and subgroup analyses of NXY-059 for acute ischemic stroke in the SAINT I trial. doi
  4. Admission glucose levels in relation to mortality and morbidity outcome in 252 stroke patients. doi
  5. Age and National Institutes of Health Stroke Scale Score within 6 hours after onset are accurate predictors of outcome after cerebral ischemia: development and external validation of prognostic models. doi
  6. (2000). Categorial Data Analysis Using the SAS System.
  7. Characteristics of blood pressure profiles as predictors of long-term outcome after acute ischemic stroke. doi
  8. Dental and periodontal status and risk for progression of carotid atherosclerosis: the inflammation and carotid artery risk for atherosclerosis study dental substudy. doi
  9. Emeribe U, for the SAINT II Investigators. NXY-059 for acute ischaemic stroke: results of the SAINT II trial. doi
  10. Enhancing the development and approval of acute stroke therapies: stroke therapy academic industry roundtable.
  11. Functional and histological evidence for the protective effect of NXY-059 in a primate model of stroke when given 4 hours after occlusion. doi
  12. (1965). Functional evaluation: the Barthel Index. Md State Med J.
  13. Group Investigators. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. doi
  14. (2002). Hemorrhagic transformation following ischemic stroke: significance, causes, and relationship to therapy and treatment. Curr Neurol Neurosci Rep. doi
  15. (2005). IL-6: an early marker for outcome in acute ischemic stroke. Acta Neurol Scand. doi
  16. (1994). Improved reliability of the NIH Stroke Scale using video training. doi
  17. (2006). Improving patient selection for clinical acute stroke trials. Cerebrovasc Dis. doi
  18. Improving trial power through use of prognosis-adjusted end points. doi
  19. Initial experience of a digital training resource for modified Rankin scale assessment in clinical trials. doi
  20. Interobserver agreement for the assessment of handicap in stroke patients. doi
  21. (1994). Intravenous Nimodipine West European Stroke Trial (INWEST) of nimodipine in the treatment of acute ischaemic stroke. Cerebrovasc Dis. doi
  22. Measurements of acute cerebral infarction: a clinical examination scale. doi
  23. NXY-059 for acute ischemic stroke. doi
  24. Prediction of creatinine clearance from serum creatinine. doi
  25. Premorbid antiplatelet use and ischemic stroke outcomes. doi
  26. Recommendations from the STAIR V meeting on acute stroke trials, technology, and outcomes. doi
  27. Reduction of tissue plasminogen activator-induced hemorrhage and brain injury by free radical spin trapping after embolic focal cerebral ischemia in rats. doi
  28. Stroke Therapy Academic Industry Roundtable (STAIR). Recommendations for standards regarding preclinical neuroprotective and restorative drug development. doi
  29. Stroke Therapy Academic Industry Roundtable. Recommendations for advancing development of acute stroke therapies: stroke therapy academic industry roundtable 3. doi
  30. (2006). Therapeutic strategies for the treatment of stroke. Drug Discovery Today. doi
  31. (1999). Underlying structure of the National Institutes of Health Stroke Scale: results of a factor analysis. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.