Planning a Multi-Center Trial of Interferon-gamma in Trauma Patients

描述（由申请人提供）：根据我们对“炎症和宿主对损伤的反应”项目中登记的严重钝性创伤患者的分析，我们的研究人员提出，大部分通常符合严重损伤患者研究纳入标准的患者不需要免疫调节治疗，也不太可能从这种治疗中获益(IFN？-葡聚糖或免疫球蛋白)。相反，有一小部分患者的临床病程较长，可以从使用生物反应调节剂的介入治疗中获益。将前一种患者纳入这种临床试验，这些患者要么不会受益，要么可能受到这种治疗的伤害，这使得确定这些干预措施对后者的有益影响变得极其困难

DESCRIPTION (provided by applicant): Based on our analysis of severe blunt trauma patients enrolled in the "Inflammation and the Host Response to Injury" Program, our investigators propose that a large proportion of patients who would generally meet the inclusion criteria for a study of severely injured patients are not in need of immunomodulatory therapy and are unlikely to benefit from such therapies (IFN?, ¿-glucan or immunoglobulin). In contrast, there exists a subset of patients who will have a protracted clinical course, and would benefit from interventional therapies with biological-response modifiers. Inclusion of the former patients in such a clinical trial who would either not benefit or might be harmed by such therapies has made it extremely difficult to identify the beneficial effects of these interventions in the latter subset of patients who would be responsive to these therapies. We believe that this failure to identify those patients a priori who may actually benefit from intervention ("personalized therapies") is one reason that clinical trials in trauma and sepsis have failed. Therefore, it is absolutely essential that a rapid prognostic be developed and used to prospectively identify those severely injured patients who would be good candidates for the immunomodulatory intervention. The overall goal of the proposed clinical trial would be to determine whether administration of IFN? will alter the clinical trajectory in a subgroup of severely injured patient identified by a prognostic indicator based on a genomic signature likely to have an adverse clinical outcome and who would benefit from such therapies. Blood samples will be collected with the goal being to determine whether rh-IFN? treatment restores an improved genomic signature associated with better outcomes. A primary clinical goal is to determine whether rh-IFN? reduces "time to recovery" and increases "organ-failure free days" in this at-risk population. PUBLIC HEALTH RELEVANCE: We propose to organize a clinical trial to determine whether administration of interferon-¿ will alter the clinical trajectory in a subgroup of severely injured patients, identified by a prognostic indicator based in part on the leukocyte genomic response to trauma as being likely to have an adverse clinical outcome and benefit from such therapies. Our overarching hypothesis is that changes in the blood leukocyte genome can be used to predict distant clinical outcomes and to detect response to therapies in patients, not only with severe trauma and critical illness. A primary objective is to determine whether rhIFN-? reduces "time to recovery" and increases "organ-failure free days" in the subgroup of patients identified by the prognostic test to be at increased risk.