An Observational Cohort Study to Determine the Impact of Alloantibodies and Antibodies to Self Antigens on Chronic Graft Function up to 5 Years After Pediatric Heart Transplantation (CTOTC-09)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 407
- 试验地点
- 9
- 主要终点
- Pulmonary capillary wedge pressure at heart catheterization
研究概览
简要总结
This is a multi-center, prospective, single cohort, observational study of pediatric heart transplant recipients designed to determine the impact of preformed versus de novo human leukocyte antigen (HLA) donor-specific antibodies (DSA), and antibodies to the self-antigens cardiac myosin and vimentin, on chronic allograft function. In addition, the investigators will explore mechanisms of action and predictors of DSA, rejection and altered pathophysiology.
详细描述
Participants that were enrolled in the CTOTC-04 study (ClinicalTrials.gov Identifier NCT01005316) are invited to enroll in this CTOTC-09 study. Conversion from the CTOTC-04 to CTOTC-09 study will occur in such a manner as to avoid/minimize discontinuity of follow-up between the planned CTOTC-04 and CTOTC-09 study visits. In addition, subjects added to the United Network for Organ Sharing (UNOS) system-or Canadian equivalent agency-at a participating study site, who are less than 21 years of age and fulfill all study eligibility criteria, will be invited to enroll in CTOTC-09.
This study focuses on the importance of antibodies against the newly transplanted heart in pediatric heart transplant recipients. The investigators aim to determine if certain antibodies lead to problems with the heart transplant. Antibodies are small proteins in the blood that the body makes to fight off infections, for example with bacteria or viruses. Since a new heart is "foreign" to the recipient's body, their immune system might try to attack it with antibodies, as if it were an infection. For many years it was thought that only white blood cells attacked the new heart, causing rejection.
Now there is new information showing that antibodies may also cause rejection or long-term damage to the heart. At this time, very little is known about how antibodies might cause problems after heart transplantation in transplant recipients younger than 21 years at the time of transplant.
This study will collect a medical history and blood samples at specified times for research. The blood samples will be used to measure antibodies in the blood, and to perform special tests to see how these antibodies might damage the heart.
Participant follow-up is from the day of the heart transplant to year 5 post-transplant.
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 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject and/or parent guardian able to understand and provide informed consent and where applicable assent
- •Planned long-term follow-up at one of the study sites
- •AND either:
- •Enrolled in the CTOTC-04 study and actively followed at one of the study sites
- •Listed at participating study sites, less than 21 years of age and not yet transplanted.
- •The inclusion criteria for enrollment of new study patients in the CTOTC-09 Protocol will be the same as the CTOTC-04 study (refer to ClinicalTrials.gov ID NCT01005316).
排除标准
- •Parental withdrawal of consent from the CTOTC-04 study
- •Past or current medical problems or findings from physical examination or laboratory testing that, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study
- •Listed for simultaneous multiple organ transplant.
结局指标
主要结局
Pulmonary capillary wedge pressure at heart catheterization
时间窗: 3 years post-transplantation
次要结局
- Time to first episode of late acute rejection(From >1 year to 5 years post-transplantation)
- Systolic and diastolic graft function(3 and 5 years)
- Other invasive cardiac hemodynamic findings at cardiac catheterization(3 and 5 years post-transplantation)
- Frequency of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin(3 years post-transplantation)
- Frequency to recurrent (two or more) late acute rejections(Up to 5 years post-transplantation)
- Frequency to first episode of late acute rejection with hemodynamic compromise(Up to 5 years post-transplantation)
- N-terminal pro-brain Natriuretic Peptide (NT-proBNP)/Brain Natriuretic Peptide (BNP)(3 and 5 years post-transplantation)
- Time course of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin.(3 years post-transplantation)
- Time to recurrent late acute rejections(Up to 5 years post-transplantation)
- Time to first episode of late acute rejection with hemodynamic compromise(Up to 5 years post-transplantation)
- Time to graft loss (death or retransplantation) after first late rejection(Up to 5 years post-transplantation)
- Variability of maintenance tacrolimus levels(Up to 5 years post-transplantation)
- Frequency of first episode of late acute rejection(From >1 year to 5 years post-transplantation)
- Time to graft loss (death or retransplantation) conditional to surviving one year post-transplantation(One year and up to 5 years post-transplantation)
- Proportion of participants with angiographic evidence of coronary artery disease(3 and 5 years post-transplantation)
- Medication Adherence Measure (MAM) after hospital discharge(Up to 5 years post-transplantation)