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（由申请人提供）：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，我们的研究人员提出，大部分患者通常符合以下研究的纳入标准：严重受伤的患者不需要免疫调节治疗，并且不太可能从此类治疗（IFNα、β-葡聚糖或免疫球蛋白）中受益，相反，有一部分患者的临床病程较长。并将受益于具有生物反应调节剂的介入治疗。将先前的患者纳入这样的临床试验中，这些患者要么不会受益，要么可能会受到此类疗法的伤害，这使得确定这些干预措施对后者的有益效果变得极其困难。 我们认为，未能预先确定哪些患者可能真正受益于干预（“个性化治疗”）是创伤和脓毒症临床试验失败的原因之一。开发快速预后并用于前瞻性地识别那些适合免疫调节干预的重伤患者是绝对必要的。拟议临床试验的总体目标是确定使用干扰素是否会改变临床轨迹。在确定的重伤患者亚组中通过基于可能产生不良临床结果的基因组特征的预后指标，将收集血液样本，目的是确定 rh-IFN 治疗是否可以恢复与更好的结果相关的改善的基因组特征？主要临床目标是确定 rh-IFN 是否会缩短该高危人群的“恢复时间”并增加“无器官衰竭天数”。 公共健康相关性：我们建议组织一项临床试验，以确定干扰素的使用是否会影响健康。将改变重伤亚组的临床轨迹 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产生不良的临床结果并从此类治疗中受益，我们的首要假设是血液白细胞基因组的变化可用于预测远期临床。主要目的是确定rhIFN-α是否会减少已确定患者亚组的“恢复时间”并增加“无器官衰竭天数”。通过预后测试面临更大的风险。