Platelet Immune Responses in Aging and Influenza and Sepsis (INVACS)
试验速览
- 阶段
- 不适用
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- 90 day mortality
研究概览
简要总结
Aging is associated with immunosenescence and impaired host defense mechanisms, contributing to influenza-related morbidity and mortality. Preliminary data demonstrate that the platelet transcriptome is markedly different between healthy subjects and influenza patients. Interferon-induced transmembrane proteins (IFITM) family members are among the transcripts significantly increased in platelets during influenza and expression of IFITM-3 is impaired in elderly subjects, a pattern associated with increased mortality. This study will build on these data and investigate if aging influences the expression of platelet IFITM family members in patients with influenza and sepsis.
This study will prospectively determine if aging alters the induction of (IFITMs) in platelets from hospitalized influenza and sepsis patients. The study will also determine if diminished expression of IFITM family members correlates with an increased risk of adverse outcomes in older influenza and sepsis patients.
详细描述
This will be a prospective observational cohort study comparing older (age≥65) and younger (age<65) influenza and sepsis patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years old at the time of enrollment
- •Meet one of the following three main criteria:
- •A. INFLUENZA (AND OTHER RESPIRATORY VIRUS) PATIENTS:
- •Patients admitted to the intensive care unit (ICU) with a primary microbiologic diagnosis of influenza (any strain) or other routinely clinically identified respiratory viruses within 1 week of symptom onset. Influenza or other respiratory virus will be diagnosed using an RT-PCR viral panel on a respiratory tract specimen, as is currently standard of care on patients admitted to the ICUs at IMC with respiratory symptoms.
- •B. SEPSIS PATIENTS:
- •Sepsis patients must have
- •Suspected or confirmed infection
- •Organ dysfunction as defined by a SOFA >= 2 above baseline (if no baseline data available, SOFA assumed to be 0)
- •C. SEPTIC SHOCK PATIENTS:
- •AFTER INFUSION OF 20ML/KG CRYSTALLOID OR EQUIVALENT, Septic shock patients must have
- •Suspected or confirmed infection
- •Lactate > 2 mmol/L
- •Receiving vasopressors
- •All patients must be enrolled into the study within 72 hours of ICU admission
- •Exclusion criteria
- •Have a congenital or acquired immunodeficiency disorder (e.g., chronic variable immune deficiency, agammaglobulinemia, hypogammaglobulinemia, leukocyte adhesion defects, IgA deficiency, etc.)
- •Have neutropenia (<1,000/mm3)
- •Have received immunosuppressant medications within the previous 30 days (e.g., prednisone or prednisone equivalent at a dose≥10mg daily for ≥14 days or any cyclosporine, TNF-alpha antagonists, tacrolimus, sirolimus, interferons, mycophenolate, biological agents, methotrexate, azathioprine, polyclonal/monoclonal antibodies, etc.)
- •Have any history of bone marrow or organ transplantation
- •Have an active malignancy (not including non-melanoma skin cancer or localized prostate cancer), or have received chemotherapy drugs within the last 6 months.
- •Have been admitted to the ICU for greater than 72 hours
- •Have a Hemoglobin level <7gm/dl
- •Have clinically significant bleeding
排除标准
- 未提供
结局指标
主要结局
90 day mortality
时间窗: 90 days
For the increased risk of mortality outcome, 90-day mortality will be the primary outcome variable. This will be modeled using mixed effects logistic regression, using days 0, 3, and 7 as repeated measurements. In this fashion, IFITM-3 and mortality are time-varying. A separate model will be fitted for the younger and older groups, since age group is expected to be collinear with IFITM-3 protein.
次要结局
- IFITM-3 mRNA(24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90.)
- 28 day mortality(28 days)
- Interferon-induced transmembrane protein expression in platelets(24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90)
研究者
Samuel Brown
Director, Center for Humanizing Critical Care
Intermountain Health Care, Inc.