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(申请人提供)：基于我们对“炎症和宿主损伤反应”计划中登记的严重钝性创伤患者的分析，我们的研究人员提出，通常符合严重损伤患者研究纳入标准的很大一部分患者不需要免疫调节治疗，并且不太可能从此类治疗(干扰素、β-葡聚糖或免疫球蛋白)中受益。相比之下，有一部分患者将具有长期的临床病程，并将受益于具有生物反应调节剂的介入治疗。将不会受益或可能受到此类疗法伤害的前一类患者纳入这样的临床试验，使得在后者中确定这些干预措施的有益效果变得极其困难。 对这些疗法有反应的患者的子集。我们认为，未能事先确定哪些患者实际上可能从干预(“个性化治疗”)中受益，这是创伤和败血症临床试验失败的原因之一。因此，开发一种快速的预后指标并用于前瞻性地识别哪些严重损伤的患者将是免疫调节干预的良好候选者是绝对必要的。拟议的临床试验的总体目标将是确定是否给予干扰素？将改变严重受伤患者亚组的临床轨迹，该亚组由基于基因组签名的预后指标确定，该基因组签名可能具有不利的临床结果，谁将从这种治疗中受益。将采集血样，目的是确定是否存在rh-干扰素？治疗恢复了与更好结果相关的改进的基因组签名。一个主要的临床目标是确定rh-干扰素？在这一高危人群中，减少了“恢复时间”，增加了“无器官衰竭的天数”。 公共卫生相关性：我们建议组织一项临床试验，以确定使用干扰素是否会改变严重创伤亚组的临床轨迹 部分基于白细胞基因组对创伤的反应的预后指标确定的患者可能会有不利的临床结果，并从此类治疗中受益。我们的主要假设是，血白细胞基因组的变化可以用来预测遥远的临床结果，并检测患者对治疗的反应，而不仅仅是严重创伤和危重疾病。主要目的是确定重组人干扰素-？在被预后测试确定为风险增加的患者亚组中，缩短了“恢复时间”，增加了“器官衰竭无衰竭天数”。