Observational Study of CMV Reactivation in Immunocompetent Children and Adult ICU Patients
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 275
- 试验地点
- 1
- 主要终点
- Risk factors associated with CMV reactivation in critically ill children and adults
研究概览
简要总结
Background. Human herpes viruses establish lifelong latency after primary infection and may reactivate in immunosuppressed patients causing significant morbidity and mortality. In immunocompetent patients, although reactivation may occur disease development is deterred by the competent host immune response. Recent studies indicate that approximately one third of CMV seropositive immunocompetent ICU patients present with CMV reactivation associated with poor outcome, potentially secondary to the stress incurred. CMV reactivation among immunocompetent critically ill children has not been assessed.
Study Hypothesis: Identifiable risk factors associated with CMV reactivation exist and may be used for future assessment of antiviral prophylaxis administration.
Aim: Primary aim is to identify risk factors associated with CMV reactivation and poor outcome in immunocompetent children and adults under severe stress. Whether CMV reactivation occurs in critically ill children and its clinical implications remains to be determined. Secondary aim is to study the role of cellular signaling pathways of inflammation and specific adaptive immunity during this process.
Work packages: A multicenter observational prospective study will be conducted among CMV seropositive pediatric and adult ICU patients. Patient clinical progress, laboratory findings, management, and complications will be recorded during the 28 days following ICU admission. Salivary free cortisol levels, plasma catecholamines, and serum cytokines levels will be measured to assess stress. CMV reactivation will be evaluated weekly by detecting CMV-DNA in peripheral blood and bronchial wash samples with real-time PCR. In a patient subsample, the nuclear factor κB and intracellular GC receptor will be measured in peripheral blood monocytes to study cellular signaling pathways of inflammation. The adaptive immune response to CMV infection following in vitro viral polypeptide stimulation will be prospectively examined in a subset of patients.
Expected Results: The study will provide original data on critically ill children. Further knowledge regarding risk factors associated with CMV reactivation and poor outcome will be accumulated. Novel information regarding the role of cellular inflammation and specific adaptive immune responses during CMV reactivation will be gathered.
详细描述
This is a multicenter prospective observational study of CMV seropositive patients (children and adults) admitted in ICU. Two pediatric and four adult ICU units in tertiary teaching hospitals will be recruiting for 48 and 36 months respectively.
Research plan Upon ICU admission, patients (group A and B) will be screened for inclusion/exclusion criteria and after written informed consent is obtained the patient will be enrolled. Clinical severity will be estimated using standardized score systems (PRISM III and APACHI II respectively). All pertinent demographic, medical history, clinical presentation and medical interventions will be entered in a database. Prior to initiating any supportive treatment (inotropes or corticosteroids) blood and saliva will be obtained for the determination of biological markers of stress. Serum and whole blood will be collected for the determination of CMV-IgG antibodies and CMV-DNA respectively. CMV seronegative patients will be excluded from further evaluation. Seropositive patients will be followed prospectively for 28 days. Weekly follow up (7th, 14th, 21st and 28th day of hospitalization) will include: clinical and laboratory evaluation, documentation of therapeutic intervention and CMV reactivation assessment (CMV-DNA detection). Stress markers will be re-examined only on day 7. On day 28 (end of follow up) the clinical outcome will be recorded.
In a random subset of patients (20 children and 20 adults) the intracellular signaling pathway of inflammation and specific immune responses will be studied.
Laboratory Methods
A) Serology for CMV: Serum CMV-IgG antibodies will be measured by Enzyme Immunoassay Method (Elisa, Abbott Laboratories) in hospital serology lab.
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
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •previously healthy children 5-16 years old (group A) and adults (group B)
- •no known immunosuppression (secondary to underlying disease or medications),
- •residence near the ICU (ability to return for follow up on day 28 post admission)
- •availability of patient guardian or first degree relative willing to provide written informed consent
排除标准
- •imminent death
- •expected ICU stay <48 hours
- •intubation prior to admission (in a different center) for >48 hours
结局指标
主要结局
Risk factors associated with CMV reactivation in critically ill children and adults
时间窗: 28 days
次要结局
- Role of cellular signaling and adaptive immunity(7 days)