Alloantibodies in Pediatric Heart Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 290
- 试验地点
- 8
- 主要终点
- Percentage of Participants Positive for Event of Death, Graft Loss or Rejection With Hemodynamic Compromise at 12 Months Post-Transplantation
研究概览
简要总结
The purpose of this study is to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity crossmatch and to compare this group with outcomes in nonsensitized heart transplant recipients.
详细描述
There is currently a renewed interest in alloantibodies in transplantation. In 1966, Kissmeyer and colleagues reported that pre-existing antibodies directed against donor cells could cause hyperacute rejection of the renal allograft. Three years later, in a landmark study, Patel and Terasaki showed that a lymphocytotoxic assay to identify donor-specific antibodies was highly predictive of acute graft failure. These observations led to the practice of performing prospective, donor-specific crossmatches by lymphocytotoxicity assay for all kidney transplants and for heart and lung transplants when the candidate has a positive panel reactive antibody (PRA) assay. A concept evolved that transplantations should not be performed across a positive cytotoxicity crossmatch. The purpose of this study is to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity crossmatch and to compare this group with outcomes in nonsensitized heart transplant recipients.
This study plans to enroll 370 pediatric heart transplant recipients over a period of 3 years. The follow-up period will last up to 3 years. All participants will be enrolled pretransplant. In the pretransplant phase, visits will occur every 6 months. These routine visits will continue until transplant or the end of the study. They will coincide with routine pretransplant status visits. At the time of transplant, the participants will be assigned to one of two groups. Group A will include participants who are allo-antibody negative (less than 10% by AHG CDC-PRA and ELISA in all DTT-treated serum samples). Cohort B will include participants who have the presence of a DTT-treated AHG CDC-PRA of greater than or equal to 10% and/or an ELISA-PRA greater than or equal to 10% in any pretransplant sample.
Both cohorts will receive standard transplantation care. This study has no interventions. All participants will undergo regular blood tests, and, those in the sensitized group will have additional blood testing performed after the transplant and lasting until the end of the study. Post-transplant visits will occur while participants are recovering in the hospital; at Months 1, 3, and 6; and annually until the study closes.
The information collected for the study include data from a physical exam, routine testing, adverse (AEs) and serious adverse (SAEs) events assessments, and blood collection. Each time a biopsy is done, the study will ask to review the biopsy tissue and to collect a sample. If stored tissue is not available, none will be collected.
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 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All participants listed for heart transplantation at participating CTOT-C study sites.
排除标准
- •Listed for multiple organ transplant
- •Inability or unwillingness of the participant or parent/guardian to give written informed consent or comply with the study protocol
- •Condition or characteristic which in the opinion of the investigator makes the participant unlikely to complete at least one year of follow-up
- •Current participation in other research studies that would, or might, interfere with the scientific integrity or safety of current study (e.g. by interference with immunosuppression management guidelines, study endpoints, excessive blood draws or SAE evaluation).
研究组 & 干预措施
Cohort A: Non-Sensitized
Cohort A will include participants who are alloantibody Luminex(TM) LABScreen. There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen. Non-sensitized recipients receive steroid-free maintenance immunosuppression:
- Induction Therapy (anti-T cell antibody induction)
- Tacrolimus (Prograf®)
- Mycophenolate Mofetil- MMF (CellCept®).
干预措施: Induction Therapy (Drug)
Cohort A: Non-Sensitized
Cohort A will include participants who are alloantibody Luminex(TM) LABScreen. There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen. Non-sensitized recipients receive steroid-free maintenance immunosuppression:
- Induction Therapy (anti-T cell antibody induction)
- Tacrolimus (Prograf®)
- Mycophenolate Mofetil- MMF (CellCept®).
干预措施: Tacrolimus (Drug)
Cohort A: Non-Sensitized
Cohort A will include participants who are alloantibody Luminex(TM) LABScreen. There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen. Non-sensitized recipients receive steroid-free maintenance immunosuppression:
- Induction Therapy (anti-T cell antibody induction)
- Tacrolimus (Prograf®)
- Mycophenolate Mofetil- MMF (CellCept®).
干预措施: Mycophenolate Mofetil (Drug)
Cohort B: Sensitized
Cohort B will include participants who are alloantibody positive (Sensitized) as determined by Luminex LabScreen for Class I or Class II with specificities identified by single antigen testing.
There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen.
Sensitized recipients receive:
- Induction Therapy (anti-T cell antibody induction)
- Intraoperative plasma exchange/pheresis
- Short-term post-operative plasmapheresis
- Post-transplant course of intravenous immunoglobulin (IVIG) therapy
- Maintenance corticosteroids (Prednisone)
- Tacrolimus (Prograf®)
- Mycophenolate Mofetil-MMF (CellCept®).
干预措施: Induction Therapy (Drug)
Cohort B: Sensitized
Cohort B will include participants who are alloantibody positive (Sensitized) as determined by Luminex LabScreen for Class I or Class II with specificities identified by single antigen testing.
There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen.
Sensitized recipients receive:
- Induction Therapy (anti-T cell antibody induction)
- Intraoperative plasma exchange/pheresis
- Short-term post-operative plasmapheresis
- Post-transplant course of intravenous immunoglobulin (IVIG) therapy
- Maintenance corticosteroids (Prednisone)
- Tacrolimus (Prograf®)
- Mycophenolate Mofetil-MMF (CellCept®).
干预措施: Tacrolimus (Drug)
Cohort B: Sensitized
Cohort B will include participants who are alloantibody positive (Sensitized) as determined by Luminex LabScreen for Class I or Class II with specificities identified by single antigen testing.
There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen.
Sensitized recipients receive:
- Induction Therapy (anti-T cell antibody induction)
- Intraoperative plasma exchange/pheresis
- Short-term post-operative plasmapheresis
- Post-transplant course of intravenous immunoglobulin (IVIG) therapy
- Maintenance corticosteroids (Prednisone)
- Tacrolimus (Prograf®)
- Mycophenolate Mofetil-MMF (CellCept®).
干预措施: Mycophenolate Mofetil (Drug)
Cohort B: Sensitized
Cohort B will include participants who are alloantibody positive (Sensitized) as determined by Luminex LabScreen for Class I or Class II with specificities identified by single antigen testing.
There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen.
Sensitized recipients receive:
- Induction Therapy (anti-T cell antibody induction)
- Intraoperative plasma exchange/pheresis
- Short-term post-operative plasmapheresis
- Post-transplant course of intravenous immunoglobulin (IVIG) therapy
- Maintenance corticosteroids (Prednisone)
- Tacrolimus (Prograf®)
- Mycophenolate Mofetil-MMF (CellCept®).
干预措施: Intraoperative plasma exchange/pheresis (Procedure)
Cohort B: Sensitized
Cohort B will include participants who are alloantibody positive (Sensitized) as determined by Luminex LabScreen for Class I or Class II with specificities identified by single antigen testing.
There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen.
Sensitized recipients receive:
- Induction Therapy (anti-T cell antibody induction)
- Intraoperative plasma exchange/pheresis
- Short-term post-operative plasmapheresis
- Post-transplant course of intravenous immunoglobulin (IVIG) therapy
- Maintenance corticosteroids (Prednisone)
- Tacrolimus (Prograf®)
- Mycophenolate Mofetil-MMF (CellCept®).
干预措施: Short-term post-operative plasmapheresis (Procedure)
Cohort B: Sensitized
Cohort B will include participants who are alloantibody positive (Sensitized) as determined by Luminex LabScreen for Class I or Class II with specificities identified by single antigen testing.
There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen.
Sensitized recipients receive:
- Induction Therapy (anti-T cell antibody induction)
- Intraoperative plasma exchange/pheresis
- Short-term post-operative plasmapheresis
- Post-transplant course of intravenous immunoglobulin (IVIG) therapy
- Maintenance corticosteroids (Prednisone)
- Tacrolimus (Prograf®)
- Mycophenolate Mofetil-MMF (CellCept®).
干预措施: Immunoglobulins, Intravenous (Drug)
Cohort B: Sensitized
Cohort B will include participants who are alloantibody positive (Sensitized) as determined by Luminex LabScreen for Class I or Class II with specificities identified by single antigen testing.
There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen.
Sensitized recipients receive:
- Induction Therapy (anti-T cell antibody induction)
- Intraoperative plasma exchange/pheresis
- Short-term post-operative plasmapheresis
- Post-transplant course of intravenous immunoglobulin (IVIG) therapy
- Maintenance corticosteroids (Prednisone)
- Tacrolimus (Prograf®)
- Mycophenolate Mofetil-MMF (CellCept®).
干预措施: Prednisone (Drug)
结局指标
主要结局
Percentage of Participants Positive for Event of Death, Graft Loss or Rejection With Hemodynamic Compromise at 12 Months Post-Transplantation
时间窗: 12 months post-transplantation
This is a composite outcome of death, graft loss or rejection with hemodynamic compromise. Rejection was considered to be with hemodynamic compromise if the rejection event had new onset echocardiographically measured from fractional shortening \<26% with ≥5% fall from last echocardiogram or the rejection event had new onset of heart failure.
次要结局
- Percentage of Participants With the Presence of Anti-HLA IgG Antibodies by Luminex SA Testing(Pre-transplantation)
- Percentage of Participants With the Presence of Anti-MICA Antibodies by Luminex TM Assay(Pre-Transplantation)
- Percentage of Participants -Overall Participant and Graft Survival(Transplantation to the end of study (up to 4 years post transplant).)
- Time From Participant Listing on Organ Wait-List to Receiving Organ Transplant, Death or De-Listing(Study enrollment to transplantation)
- Percentage of Participants Experiencing Acute Rejection(Transplantation to the end of study.)
- Time to Post-Transplantation Lymphoproliferative Disorder(Transplantation to the end of study (up to 4 years post transplant).)
- Percentage of Participants- Mortality While on Transplantation Wait-List(Pre-transplantation)
- Percentage of Participants -Quantification of Anti-HLA IgG Antibodies by Luminex SA Testing(Pre-transplantation)
- Presence of C4d on Endomyocardial Biopsy (EMB)(Transplantation to the end of study (up to 4 years post transplant).)
- Percentage of Participants Positive for Severe Infection(s)(Transplantation to the end of study (up to 4 years post transplant).)
- Time to Production of Post-Transplant de Novo Donor-specific Alloantibodies(Transplantation to first year post transplant (up to 12 months post transplant).)
- Percentage of Participants Positive for de Novo Donor-Specific Alloantibody Production in the First Year Post-Transplantation(Transplantation to first year post transplant (up to 12 months post transplant).)
- Percentage of Participants With Occurrence of Re-Hospitalization(s)(Transplantation to the end of study (up to 4 years post transplant).)
- Time to Diagnosis of Chronic Rejection(Transplantation to the end of study (up to 4 years post transplant).)
- Time to New-Onset Diabetes Mellitus(Transplantation to the end of study (up to 4 years post transplant).)
- Time to Acute Rejection(Transplantation to the end of study.)