New drug for stroke patients

• A new drug, NXY-059, could aid the recovery of stroke patients reported two newspapers on 9 February 2006 (1,2).

• A multinational trial of NXY-059 versus placebo for the reduction of disability after stroke was the basis for the newspaper reports. The results of the trial showed a twenty percent reduced likelihood of disability after being given NXY-059 compared with being given placebo at 90 days following stroke (3). No improvements were found in neurological functioning and ability to perform tasks independently. Mortality and rates of adverse events were similar in the treatment and placebo groups.

• The Sun (1) provided a brief but accurate report of this well-conducted trial. The findings of the trial appear reliable. The Daily Express (2) stated that the new drug increased the chances of survival. However this was not a finding of the trial. Although the headline was overly optimistic in its use of the word 'Miracle', the article did correctly state that the new drug will not be commercially available for some time.

Evaluation of the evidence base for NXY-059 for Acute Ischemic Stroke

Where does the evidence come from?

The evidence comes from the Stroke-Acute Ischemic NXY Treatment (SAINT I) trial and was conducted in 154 hospitals across 24 countries. The research was led by Professor Kennedy R Lees of the Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Western Infirmary, Glasgow. The trial was funded by Astra-Zeneca. The academic authors vouch for the veracity and completeness of the data and data analysis.

What were the authors' objectives?

To assess whether the drug NXY-059 would reduce disability in patients following acute ischaemic stroke.

What was the nature of the evidence?

SAINT I was a multicentre randomised double-blind placebo controlled trial. The trial included 1722 patients with acute ischemic stroke. Patients were eligible for inclusion if they were conscious, aged over 18, had a clinical diagnosis of acute stroke, had limb weakness and a score of at least six on the National Institutes of Health Stroke Scale (NIHSS).

What interventions were examined in the research?

Patients were randomised to receive a 72 hour infusion of placebo or intravenous NXY-059 within six hours after the onset of stroke.

The main outcome of interest was disability at 90 days according to the modified Rankin Scale. The scale ranges from 0 (no symptoms) to 5 (severe disability requiring constant care and bedridden). Assessment was made at 24 and 72 hours and at 7, 30 and 90 days. Other outcomes of interest included neurological improvements, measures of independence, mortality and adverse events.

What were the findings?

At 90 days, there was a twenty percent reduced likelihood of disability in those given NXY-059 compared with those given placebo based on the modified Rankin Scale.

No improvements in neurological functioning were noted on the NIHSS or in independence as rated by the Barthel Index. Mortality and rates of serious and non-serious adverse events were similar in the treatment and placebo groups.

What were the authors' conclusions?

The authors concluded that, although NXY-059 administered within six hours of acute ischaemic stroke reduced disability at 90 days according to the modified Rankin scale, further research is needed to determine its potential benefits for stroke patients.

How reliable are the conclusions?

This large multicentre trial appears to have used appropriate methods in its design and analysis, and to have been well conducted. Clear details were given for all participants included in the study indicating that the numbers who withdrew from the trial or were lost to follow-up or received an unassigned treatment were small. The study groups were comparable at baseline. The conclusions are therefore likely to be reliable.

The authors state that a further trial, SAINT II, is under way with the aim of confirming the findings of the present study in a larger sample.

Systematic reviews

Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.

There were no related systematic reviews identified on the Cochrane Database of Systematic Reviews (CDSR) or on the Database of Abstracts of Reviews of Effects (DARE).

References and resources

1. Drug bid for stroke. The Sun, 9 February 2006, p15.

2. 'Miracle' drug may save stroke victims. Daily Express, 9 February 2006, p13.

3. Lees KD, Zivin JA, Ashwood T, Davalos A, Davis SM, Diener H, Grotta J, Lyden P, Shuaib A, Hardemark H, Wasiewski WW for the Stroke–Acute Ischemic NXY Treatment (SAINT I) Trial Investigators. NXY-059 for Acute Ischemic Stroke. New England Journal of Medicine, 2006;354(6):588-600.

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