PITFALLS AND ADVANCES FROM THE INTERNATIONAL TIRILAZAD TRIAL IN MODERATE AND SEVERE HEAD-INJURY

This manuscript reviews current experience with a large-scale clinical trial of the nonglucocorticoid 21-aminosteroid compound, tirilazad me sylate (U-74,006F). The trial itself now encompasses 15 countries with all central coordination conducted in the Data Coordinating Center at the University of California, San Diego. To date, the conduct of this trial has shown that diverse groups of clinicians in multiple countri es have been able to work together to adhere to a tightly defined rese arch protocol. Despite the success in initiating and conducting this t rial, however, there have been several unanticipated problems that hav e complicated its progress. In this regard, difficulties have been ass ociated with the use of mean Glasgow coma scores for data analysis. Si milarly, a prospective identification of the risk variables was found necessary to preclude the potential for serious errors in data analysi s. Lastly, a differential effect of the drug was noted in women compar ed to men in the European subarachnoid hemorrhage trial where a signif icant improvement in outcome was observed in males. This differential response appears to be linked to drug metabolism, but the problem may be further compounded by improper dosing because of failure to weigh m any patients. Women appear to be routinely underdosed because their we ights are routinely underestimated. Overall, this paper shows the feas ibility of conducting such a large scale international trial, while al so highlighting some of the potential pitfalls and problems that shoul d be avoided in future trials of this nature.