title: Termination of the Department of Veterans Affairs Cooperative Study of steroid therapy for systemic sepsis.
abstract: The Department of Veterans Affairs Cooperative Study Program conducted a randomized, double-masked trial of steroid therapy versus placebo therapy for patients with systemic sepsis from 1983 to 1986. Treatment was initiated as soon as sepsis was recognized and before results of cultures confirmed infection. The original hypothesis was to test the effect of therapy on short-term (14-day) mortality in patients with gram-negative bacteremia. Because therapy had to begin before culture results were available, all septic patients had to be enrolled. Consequently, the study was modified to evaluate therapy in all patients with sepsis, and by post-stratification in those with gram-negative bacteremia. Patient enrollment was planned to continue for 3.5 years to achieve a sample size of 276 patients. After 223 patients were randomized, 14-day mortalities were 22% in the placebo-treated group versus 21% in the steroid-treated group (p = 0.97). In contrast, for the 51 patients with gram-negative bacteremia, mortalities were 27% placebo-treated versus 7% steroid-treated (p = 0.11). The Data Monitoring Board recommended continuation of the trial to evaluate what appeared to be an emerging gram-negative trend, but the Cooperative Studies Evaluation Committee decided to end the trial 12 months early because of the lack of efficacy in all septic patients. The reasons for the proposed extension and for the termination of the trial are presented. The more general problem of evaluating a biologically important subgroup imbedded in a large clinical trial is also discussed.
authors.affiliation: Cooperative Studies Program Coordinating Center, Department of Veterans Affairs Medical Center, West Haven, CT.
authors.forename: P
authors.initials: P
authors.lastname: Peduzzi
mesh_terms: D001424:Bacterial Infections / Q000188:drug therapy* / Q000401:mortality; D002986:Clinical Trials as Topic / Q000379:methods; D004311:Double-Blind Method; D006090:Gram-Negative Bacteria / Q000302:isolation & purification*; D006094:Gram-Positive Bacteria / Q000302:isolation & purification*; D006801:Humans; D008775:Methylprednisolone / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D014481:United States; D014493:United States Department of Veterans Affairs
chemical_list: D008775:Methylprednisolone