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

计划在创伤患者中进行干扰素-γ 多中心试验

• 批准号: 8366828
• 负责人: RONALD GARY TOMPKINS
• 金额: $ 17.21万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8366828
• 关键词: Acute; Address; Applications Grants; Area; Award; Bioinformatics; Biological; Biological Response Modifiers; Biomedical Research; Blood Transfusion; Blood specimen; Blunt Trauma; Budgets; Caring; Case Report Form; Clinical; Clinical Research; Clinical Trials; Consent Forms; Critical Illness; Data; Diagnosis; Distant; Documentation; Elements; Enrollment; Epidemiology; Exclusion Criteria; Failure; Feedback; Funding; Funding Opportunities; Gene Expression Profile; Genes; Genome; Genomics; Glucans; Glues; Goals; Grant; Hospitals; Hour; Human; Immune response; Immunoglobulins; Immunologics; Individual; Inflammation; Inflammatory Response; Injury; Institutional Review Boards; Interferon Type II; Interferons; Intervention; Leukocytes; Metabolic; Monitor; Multi-Institutional Clinical Trial; Multiple Organ Failure; National Institute of General Medical Sciences; Organ failure; Outcome; Patients; Physiological; Population; Populations at Risk; Process; Proteomics; Protocols documentation; Recovery; Regulation; Regulatory Element; Relative (related person); Research; Research Design; Research Personnel; Risk; Role; Safety; Sample Size; Science; Sepsis; Solutions; Staging; Statistical Data Interpretation; Subgroup; System; Technology; Testing; Therapeutic Intervention; Time; Trauma; Travel; Work; base; clinical infrastructure; improved; inclusion criteria; injured; interest; intervention effect; meetings; mortality; multi-site trial; performance site; prognostic; prognostic indicator; programs; response; response to injury; skills

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.

描述（适用于适用）：根据我们对参加“炎症和宿主对伤害的反应”计划的严重钝性创伤患者的分析，我们的研究人员建议，很大一部分患者通常符合纳入标准以进行严重受伤的患者的研究，不需要免疫治疗并受益于此类治疗方法（如果是这样的IFM），或者是ifm imm imm impy吗？对比，存在一部分患者，这些患者将具有长期的临床病程，并且将受益于生物反应修饰剂的介入疗法。将前患者纳入这样的临床试验中，他们要么不会受益，要么可能会受到这种疗法的伤害，因此很难确定这些干预措施在以后的 对这些疗法有反应的患者子集。我们认为，这种未能将这些患者识别为实际上可能从干预中受益的患者（“个性化疗法”）是创伤和败血症中临床试验失败的原因之一。因此，绝对必须开发快速预后，并用来识别那些将成为免疫调节干预的良好候选者的严重受伤的患者。拟议的临床试验的总体目标是确定是否给予IFN？将根据可能具有不良临床结果并从这种疗法中受益的基因组信号，从预后指标确定的严重受伤的患者亚组中改变临床轨迹。将收集血液样本，目的是确定RH-IFN是否？治疗恢复了与更好的结果相关的改进基因组特征。一个主要的临床目标是确定RH-IFN是否？在这种高危人群中，减少了“恢复时间”，并增加了“恢复时间”。 公共卫生相关性：我们建议组织一项临床试验，以确定干扰素的给药是否会改变严重受伤的亚组中的临床轨迹 通过预后指标确定的部分基于白细胞基因组反应对创伤的患者可能具有不良的临床结果并受益于这种疗法。我们的总体假设是，血清细胞基因组的变化可用于预测不同的临床结果并检测患者对疗法的反应，不仅是严重的创伤和危重疾病。一个主要目的是确定rhifn-是否？减少了“恢复时间”，并增加了通过预后测试确定的患者亚组的“无机日子”，其风险增加。