New Trial(s) on Antiedema Treatment in Stroke?
To the Editor:
We read with interest the Controversies in Stroke on steroids,1 and appreciated both Dr Norris’ and Dr Poungvarin’s papers. We fully agree with the conclusion of Drs Davis and Donnan, in that when no commercial attraction exists for some treatment, then only high-quality, investigator-driven trials are possible. However, we wish to stress the fact that if someone is interested in planning such a trial on antiedema treatment for stroke patients, he or she should first look at the available evidence and choose the most promising drug, with the higher probability of a positive result. Therefore, looking at the Cochrane Library, it seems to us that it is glycerol, and not steroids, that should be the first choice for a new trial on antiedema treatment in acute stroke. In fact,2 glycerol has been studied in ten trials with a total of 945 patients (almost double the number as compared with steroids). There was a nonsignificant reduction in the odds ratio (OR) of death within the scheduled treatment period (OR 0.78, CI 0.58/1.06), which was significant for ischemic stroke (OR 0.65, CI 0.44/0.97) and for truly randomized studies (OR 0.69, CI 0.47/1). No significant result, however, was obtained for long-term outcome. The drug had almost no side effect (another point of superiority as compared with steroids!). We know that glycerol is almost never used in the Anglo-Saxon and Scandinavian countries, but it is, however, still popular in Italy, Poland,3 and China. Since a trial should include at least 2000 people to have enough power to detect a clinically significant effect on long-term outcome, we are discussing with the Italian stroke patient association (ALICE) the possibility of such an independent study; however, a possible international collaboration is seen with interest. Those who want to read the first draft of the protocol can write to us.
Norris J, Poungvarin N, Davis S, Donnan G. Controversies in Stroke. Stroke. 2004; 35: 228–231.
Righetti E, Celani MG, Cantisani TA, Sterzi R, Boysen G, Ricci S. Glycerol in acute stroke (Cochrane Review). In The Cochrane Library, issue 4, 2003. Oxford: Update Software.
Ricci S. Between-country variation in the use of medical treatment for acute stroke. Cerebrovasc Dis. 1995; 5: 272.