A New Biomarker for the Non-invasive Diagnosis of Rejection After Heart Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 134
- 试验地点
- 4
- 主要终点
- Comparison of donor-derived cell-free DNA and endomyocardial biopsy with respect to rejection
研究概览
简要总结
This study is a prospective, observational multi-center cohort study. The study will consist of patients undergoing heart transplantation. The main purpose is to test a new biomarker for rejection against the gold-standard, the endomyocardial biopsy (EMB). 80 patients will be included, both children and adults.
详细描述
The primary objective is a comparison of an the established, invasive diagnostic test, the endomyocardial biopsy (EMB) against a new, non-invasive test. The new test is the measurement of donor-derived cell-free DNA (dd-cfDNA) circulating in the blood stream of the recipient, quantified by droplet digital PCR (polymerase-chain reaction) after targeted multiplex preamplification. Sensitivity is calculated with EMB as the gold standard. The patients will be followed during one year post-transplantation with simultaneous blood samples and EMB. The patients will further be followed clinically for 5 years. A suitable cut-off for the ratio of dd-cfDNA will be calculated using receiver operating characteristic (ROC) analysis.
Secondary objectives are description of patient outcomes with respect to organ function, quality of life and adverse events.
Secondary objectives are the calculation of the costs related to the transplantation process as well as to the follow-up with EMB. A simulation will be done with respect to possible savings achieved if the new biomarker could be implemented.
The study consists of two cohorts: all adult recipients of heart transplantation at Sahlgrenska University Hospital (one of two center conducting heart transplantation in Sweden): regional study. The other cohort consists of all children undergoing heart transplantation in Sweden:national study. Patients will undergo transplantation at Sahlgrenska University Hospital in Gothenburg as well as at Skåne University Hospital in Lund. Follow-up with blood samples and EMB of these patients will be in Gothenburg, Lund and at Karolinska University Hospital in Stockholm.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient on waiting list for heart transplantation
- •Signed informed consent
排除标准
- •Follow-up outside Sweden
结局指标
主要结局
Comparison of donor-derived cell-free DNA and endomyocardial biopsy with respect to rejection
时间窗: 3 years
Measurement of both fraction of donor-derived cell-free DNA of all cell-free DNA (derived from recipient and donor) as well as the absolute number of copies per ml plasma derived from the donor. Comparison is made with simultaneously obtained endomyocardial biopsies that are graded with respect to rejection, according to the official guidelines provided by the International Society of Heart and Lung Transplantation.
次要结局
- Immunization status(5 years)
- Prior cardiac surgery(5 years)
- Overweight(5 years)
- Circulatory support to transplantation(5 years)
- Malignancy(5 years)
- Initial immunosuppression and malignancy(5 years)
- Survival(3 years)
- Neonatal cardiac surgery(5 years)
- Cost analysis 1(5 years)
- Rejection(5 years)
- Graft-vasculopathy(5 years)
- Quality of life(5 years)
- GFR (glomerular filtration rate)(5 years)
- Donor cardiac arrest(5 years)
- Initial immunosuppression(5 years)
- Ischemia time(5 years)
- Re-transplantation(5 years)
- Infections(5 years)
- Donor cardiopulmonary resuscitation (CPR) impact(3 years)
- Immunosuppression and adverse effects(5 years)
- Immunosuppression and rejection(5 years)
- Blood products and adverse events(5 years)