Rationale, design and performance of a clinical trial to investigate interferon-gamma (Imukin) in the prophylactic treatment of severe burns-related infections.

Recent advances in resuscitation therapy have increased the survival rate of patients with severe burns in the burn shock phase. Infectious complications represent the major cause of death in patients with extensive burns, however, in spite of the application of early and aggressive interventions. Extensive burn injury causes profound alterations in various essential elements of the normal host immune response and the main aim of treatment after resuscitation is to maintain or even improve host resistance. The positive anti-infective effects of interferon (IFN)-gamma observed in animal models and in clinical studies, for example in chronic granulomatous disease, provided the rationale for a study to investigate its use in patients with severe burns. A study was therefore designed to determine the efficacy and tolerance of IFN-gamma in preventing death related to infection in patients with severe burn injury who are at risk of infection. In order to avoid unnecessary risk for patients and reduce the cost, a sequential design was chosen. The primary end-point was reviewed in a group sequential manner after every 60 patients through an independent monitoring board. The study was a randomised, double-blind, Phase III multi-centre trial, conducted at 23 European Burn Centres. An interval censored survival time approach was taken, using information collected at days 8, 15, 30, 60, and 90. The trial is still blinded, but the rationale for conducting the study and its design are discussed.