Optimal Pediatric Heart Transplant Immunosuppression With MicroRNAs
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 8
- 主要终点
- Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Infection in Pediatric Heart Transplant Recipients
研究概览
简要总结
This study aims to discover circulating microRNAs (associated with drug doses and levels) that can be used to characterize the overall immune state in pediatric heart transplant patients and predict patients that will go on to develop infection and rejection. MicroRNAs (miRs) are small, non-coding RNA molecules that regulate gene expression and serve as molecular biomarkers found in the circulation.
详细描述
The study objectives will be accomplished in a prospective, multicenter observational, longitudinal cohort study that includes 100-150 Pediatric Heart Transplant (PHT) patients from the United States. Patients will be screened for eligibility and enrolled 10-50 days after PHT. Study participation will last 24 months.
All patients will follow the center's standard of care surveillance schedule after transplant. Blood samples will be collected for miR evaluation at:
- specified time intervals after transplant and
- when a clinical event of interest occurs, including treated rejection, or infection.
Research samples will be collected and used to evaluate microRNA expression as well as other biomarkers related to heart transplantation and immunosuppression medications. Additional data collection will include demographics, medical history, medications, human leukocyte (HLA)/donor specific antibody (DSA) evaluations, endomyocardial biopsy (EMB), echocardiography, donor-derived cell-free DNA (dd-cfDNA), and other post-transplant events and testing.
This work will form the basis for a non-invasive, genomic blood test that can be used to monitor patients after heart transplant to mitigate complications of over-immunosuppression, such as infection, without increasing the risks of under-immunosuppression, such as rejection.
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≤ 18 years at time of transplant listing
- •Subject is within 10-50 days post-orthotopic heart transplant at time of enrollment.
- •Planned follow-up at the transplant center for a minimum of one-year.
- •Caregiver able and willing to comply with the study visit schedule, study procedures, and study requirements.
排除标准
- •Recipient of a multi-organ transplant
- •History of prior solid organ transplant before the index heart transplant
- •Ongoing mechanical circulatory support or hemodynamic instability after transplant
- •Active infection requiring either a) hospitalization or b) treatment with antimicrobial drugs (does not include prophylaxis for infection or suppressive antibiotics given after transplant)
- •History of treated rejection prior to study enrollment
- •Inability to collect specified blood volume after enrollment and prior to 50 days post-transplant
结局指标
主要结局
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Infection in Pediatric Heart Transplant Recipients
时间窗: up to 2 years post-transplant
A time-to-event analysis will be performed to identify specific circulating microRNAs (miRs) that predict the risk of infection in heart transplant recipients. Infections are defined as any bacterial, viral, fungal, or opportunistic infection leading to: 1) hospitalization, 2) prescription of antimicrobial therapy, or 3) reduction in immunosuppression.
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Rejection in Pediatric Heart Transplant Recipients
时间窗: up to 2 years post-transplant
A time-to-event analysis will be performed to identify specific circulating microRNAs (miRs) that predict the risk of rejection in heart transplant recipients. Rejection is defined as treated rejection based on 1) endomyocardial biopsy (EMB) pathology, 2) unexplained graft dysfunction, or 3) molecular testing; leading to treatment with pulse dose steroids, monoclonal antibodies, plasmapheresis, and/or intravenous immunoglobulin (IVIg).
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Infection in Pediatric Heart Transplant Recipients
时间窗: up to 2 years post-transplant
A time-to-event analysis will be performed to identify specific circulating microRNAs (miRs) that predict the risk of infection in heart transplant recipients. Infections are defined as any bacterial, viral, fungal, or opportunistic infection leading to: 1) hospitalization, 2) prescription of antimicrobial therapy, or 3) reduction in immunosuppression.
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Rejection in Pediatric Heart Transplant Recipients
时间窗: up to 2 years post-transplant
A time-to-event analysis will be performed to identify specific circulating microRNAs (miRs) that predict the risk of rejection in heart transplant recipients. Rejection is defined as treated rejection based on 1) endomyocardial biopsy (EMB) pathology, 2) unexplained graft dysfunction, or 3) molecular testing; leading to treatment with pulse dose steroids, monoclonal antibodies, plasmapheresis, and/or intravenous immunoglobulin (IVIg).
次要结局
未报告次要终点
研究者
Palak Shah
Professor
Northwestern University